<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02186847</url>
  </required_header>
  <id_info>
    <org_study_id>NRG-LU001</org_study_id>
    <secondary_id>NCI-2014-01071</secondary_id>
    <secondary_id>PNRG-LU001_A01PAMDREVW01</secondary_id>
    <secondary_id>NRG-LU001</secondary_id>
    <secondary_id>NRG-LU001</secondary_id>
    <secondary_id>U10CA180868</secondary_id>
    <nct_id>NCT02186847</nct_id>
  </id_info>
  <brief_title>Chemotherapy and Radiation Therapy With or Without Metformin Hydrochloride in Treating Patients With Stage III Non-small Cell Lung Cancer</brief_title>
  <official_title>Randomized Phase II Trial of Concurrent Chemoradiotherapy +/- Metformin HCL in Locally Advanced NSCLC</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>NRG Oncology</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>NRG Oncology</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This randomized phase II trial studies how well chemotherapy and radiation therapy given with&#xD;
      or without metformin hydrochloride works in treating patients with stage III non-small cell&#xD;
      lung cancer. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in&#xD;
      different ways to stop the growth of tumor cells, either by killing the cells, by stopping&#xD;
      them from dividing, or by stopping them from spreading. Radiation therapy uses high-energy&#xD;
      x-rays to kill tumor cells and shrink tumors. Metformin hydrochloride may shrink tumors and&#xD;
      keep them from coming back. It is not yet known whether chemotherapy and radiation therapy is&#xD;
      more effective when given with or without metformin hydrochloride in treating stage III&#xD;
      non-small cell lung cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To determine whether metformin hydrochloride (MET) added to chemoradiotherapy can improve&#xD;
      progression-free survival (PFS) in patients with locally advanced non-small cell lung cancer&#xD;
      (NSCLC).&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. Determine the effects of MET on overall survival (OS), time to local-regional progression&#xD;
      (LRP), and time to distant metastasis (DM).&#xD;
&#xD;
      II. Evaluate the effect of MET on chemoradiotherapy toxicity (Common Terminology Criteria for&#xD;
      Adverse Events, version 4 [CTCAE, v. 4]) within 1 year of completion of all treatment.&#xD;
&#xD;
      III. Collect biospecimens to develop biomarkers of MET activity.&#xD;
&#xD;
      OUTLINE: Patients are randomized to 1 of 2 treatment arms.&#xD;
&#xD;
      After completion of study treatment, patients are followed up at 4-6 weeks, every 3 months&#xD;
      for 2 years, every 6 months for 3 years, and then annually thereafter.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date>August 2014</start_date>
  <completion_date type="Anticipated">April 16, 2024</completion_date>
  <primary_completion_date type="Actual">April 16, 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Participants Alive Without Progression (Progression-free Survival)</measure>
    <time_frame>From randomization to last follow-up. Maximum follow-up at time of analysis was 47.2 months.</time_frame>
    <description>Progression is defined per RECIST v1.1 as change in a known lesion(s) meeting one of the following criteria: [1] At least a 20% increase in the sum of the longest diameter of target lesions such that the absolute increase must be &gt; 5 mm. [2] Appearance of ≥1 new lesions. Progression-free survival time is defined as time from randomization to the date of first progression, death, or last known follow-up (censored). Progression-free survival rates are estimated using the Kaplan-Meier method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. One-year rates are provided. Analysis occurred after 102 progression-free survival events were reported.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Alive (Overall Survival)</measure>
    <time_frame>From randomization to last follow-up. Maximum follow-up at time of analysis was 47.2 months.</time_frame>
    <description>Overall survival time is defined as time from randomization to the date of death from any cause or last known follow-up (censored). Overall survival rates are estimated using the Kaplan-Meier method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. One-year rates are provided. Analysis occurred after 102 progression-free survival events were reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Local-regional Progression</measure>
    <time_frame>From randomization to last follow-up. Maximum follow-up at time of analysis was 47.2 months.</time_frame>
    <description>Local-regional progression (LRP) is defined as progression within the planned treatment volume (PTV) or outside the PTV but within the same lobe(s) of the lung as the primary tumor or in regional lymph nodes. Progression is defined as change in a known lesion(s) meeting one of the following criteria: [1] ≥ 20% increase in the sum of the longest diameter of target lesions such that the absolute increase must be &gt; 5 mm. [2] Appearance of ≥1 new lesions. LRP time is defined as time from randomization to the date of first LRP, death without LRP (competing risk), or last known follow-up (censored). LRP rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. One-year rates are provided. Analysis occurred after 102 LRP events were reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Distant Metastases</measure>
    <time_frame>From randomization to last follow-up. Maximum follow-up at time of analysis was 47.2 months.</time_frame>
    <description>Distant metastasis (DM) is defined as the appearance of ≥ 1 new lesions at any site (including pleural or pericardial effusion) outside of the following: the planned treatment volume, the same lobe(s) of the lung as the primary tumor, or regional lymph nodes. Time to DM is defined as time from randomization to the date of first DM, death without DM (competing risk), or last known follow-up (censored). DM rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. One-year rates are provided. Analysis occurred after 102 progression-free survival events were reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Treatment-related Grade 3 or Higher Adverse Events</measure>
    <time_frame>From start of treatment to last follow-up. Maximum follow-up at time of analysis was 47.2 months.</time_frame>
    <description>Adverse events (AE) were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to adverse event. &quot;Treatment-related&quot; is defined definitely, probably, or possibly related to treatment.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">170</enrollment>
  <condition>Adenosquamous Lung Carcinoma</condition>
  <condition>Bronchioloalveolar Carcinoma</condition>
  <condition>Large Cell Lung Carcinoma</condition>
  <condition>Lung Adenocarcinoma</condition>
  <condition>Non-Small Cell Lung Carcinoma</condition>
  <condition>Recurrent Non-Small Cell Lung Carcinoma</condition>
  <condition>Squamous Cell Lung Carcinoma</condition>
  <condition>Stage IIIA Non-Small Cell Lung Cancer</condition>
  <condition>Stage IIIB Non-Small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Chemoradiation</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>60 Gy Radiation therapy with concurrent paclitaxel and carboplatin followed by consolidation paclitaxel and carboplatin</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Metformin + Chemoradiation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Metformin plus 60 Gy Radiation therapy with concurrent paclitaxel and carboplatin followed by consolidation paclitaxel and carboplatin</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Radiation Therapy</intervention_name>
    <description>Radiation therapy (RT) is given in 2 Gy fractions once daily 5 days per week to a total of 30 fractions and 60 Gy. Photons required; 3-dimensional conformal radiation therapy (3D-CRT) or intensity-modulated radiation therapy (IMRT) permitted. Starts within 14 days of randomization (Chemoradiation arm) or 14 days after metformin starts (Chemoradiation + Metformin arm).</description>
    <arm_group_label>Chemoradiation</arm_group_label>
    <arm_group_label>Metformin + Chemoradiation</arm_group_label>
    <other_name>3-dimensional conformal radiation therapy</other_name>
    <other_name>3D-CRT</other_name>
    <other_name>Intensity-modulated radiation therapy</other_name>
    <other_name>IMRT</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carboplatin</intervention_name>
    <description>2 AUC (area under the curve) via IV weekly on days 1, 8, 15, 22, 29, and 36 from start of radiation therapy. Two 21 day cycles of 6 AUC via IV starting 28-42 days after the end of radiation therapy.</description>
    <arm_group_label>Chemoradiation</arm_group_label>
    <arm_group_label>Metformin + Chemoradiation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin</intervention_name>
    <description>Metformin is taken orally. Dose escalation begins 2 weeks prior to the initiation of chemoradiation. 500 mg twice daily days 1-7 of metformin. 500 mg three times daily days 8-14 of metformin. Three times a day with the following dosage: 500mg in the morning, 1000mg at noon, and 500mg in the evening concurrent with chemoradiation and through consolidation chemotherapy (days 15-126 of metformin),</description>
    <arm_group_label>Metformin + Chemoradiation</arm_group_label>
    <other_name>Metformin HCL</other_name>
    <other_name>Metformin Hydrochloride</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Paclitaxel</intervention_name>
    <description>50 mg/m2 via IV weekly on days 1, 8, 15, 22, 29, and 36 from start of radiation therapy. Two 21 day cycles of 200 mg/m2 via IV 28-42 days after the end of radiation therapy.</description>
    <arm_group_label>Chemoradiation</arm_group_label>
    <arm_group_label>Metformin + Chemoradiation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Pathologically (histologically or cytologically) proven diagnosis of stage IIIA or&#xD;
             IIIB non-small cell lung cancer within 84 days of registration; eligible histologies&#xD;
             include adenocarcinoma, adenosquamous, large cell carcinoma, squamous carcinoma,&#xD;
             non-lobar and non-diffuse bronchoalveolar cell carcinoma or non-small cell lung cancer&#xD;
             not otherwise specified)&#xD;
&#xD;
          -  Patients must have measurable disease&#xD;
&#xD;
          -  Patients must have unresectable disease, be medically inoperable, or unwilling to&#xD;
             undergo surgical management&#xD;
&#xD;
          -  Appropriate stage for protocol entry, including no distant metastases, based upon the&#xD;
             following minimum diagnostic workup:&#xD;
&#xD;
               -  History/physical examination, including documentation of height, weight, body&#xD;
                  surface area, and vital signs, within 30 days prior to registration&#xD;
&#xD;
               -  Computed tomography (CT) with IV contrast or magnetic resonance imaging (MRI)&#xD;
                  imaging (if CT scan with contrast is medically contraindicated) of the lung and&#xD;
                  upper abdomen through the adrenal glands, required within 45 days prior to&#xD;
                  registration (recommended within 30 days prior to registration&#xD;
&#xD;
               -  MRI of the brain with contrast (or CT with contrast if MRI is medically&#xD;
                  contraindicated) within 45 days prior to registration; note: the use of&#xD;
                  intravenous contrast is required for the MRI or CT; an MRI without contrast is&#xD;
                  only permitted if the patient has a contrast allergy&#xD;
&#xD;
               -  Whole-body fludeoxyglucose (FDG)-positron emission tomography (PET)/CT required&#xD;
                  within 45 days prior to registration (recommended within 30 days prior to&#xD;
                  registration; note: patients do not need to have a separate CT of the chest and&#xD;
                  upper abdomen with contrast if PET/CT imaging includes a high quality CT with&#xD;
                  contrast&#xD;
&#xD;
          -  Zubrod performance status 0-1&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt;= 1,500 cells/mm^3&#xD;
&#xD;
          -  Complete blood count(CBC)/differential obtained within 14 days prior to registration&#xD;
             on study, with adequate bone marrow function defined as follows:&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3&#xD;
&#xD;
               -  Platelets &gt;= 100,000 cells/mm^3&#xD;
&#xD;
               -  Hemoglobin &gt;= 8.0 g/dl (note: the use of transfusion or other intervention to&#xD;
                  achieve hemoglobin [Hgb] &gt;= 8.0 g/dl is acceptable)&#xD;
&#xD;
          -  Adequate renal function within 14 days prior to registration, defined as serum&#xD;
             creatinine within normal institutional limits or creatinine clearance must be at least&#xD;
             60 ml/min;&#xD;
&#xD;
          -  Adequate hepatic function within 14 days prior to registration, defined as total&#xD;
             bilirubin ≤ 1.5 x upper limit of normal (ULN) for the institution and alanine&#xD;
             aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase ≤&#xD;
             2.5 x ULN for the institution;&#xD;
&#xD;
          -  Fasting blood glucose ≤ 125 mg/dL within 14 days prior to registration;&#xD;
&#xD;
          -  Serum albumin &gt; 3.0 g/dl within 14 days prior to registration;&#xD;
&#xD;
          -  For women of childbearing potential, a serum pregnancy test within 72 hours prior to&#xD;
             registration;&#xD;
&#xD;
          -  Patients with post-obstructive pneumonia are eligible provided they no longer require&#xD;
             intravenous antibiotics at registration;&#xD;
&#xD;
          -  Patients must be at least 3 weeks from prior thoracotomy (if performed);&#xD;
&#xD;
          -  If a pleural effusion is present, the following criteria must be met at registration&#xD;
             to exclude malignant involvement (incurable M1a disease):&#xD;
&#xD;
               -  When pleural fluid is visible on both the CT scan and on a chest x-ray, a&#xD;
                  pleuracentesis is required to confirm that the pleural fluid is cytologically&#xD;
                  negative;&#xD;
&#xD;
               -  Effusions that are minimal (i.e. not visible under ultrasound guidance) and that&#xD;
                  are too small to safely tap are eligible.&#xD;
&#xD;
          -  Women of childbearing potential and male participants must practice adequate&#xD;
             contraception throughout the study;&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with mixed small cell and non-small cell histologies&#xD;
&#xD;
          -  Patients with distant metastasis&#xD;
&#xD;
          -  Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free&#xD;
             for a minimum of 3 years (for example, carcinoma in situ of the breast, oral cavity,&#xD;
             or cervix are all permissible)&#xD;
&#xD;
          -  Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a&#xD;
             different cancer is allowable&#xD;
&#xD;
          -  Prior radiotherapy to the region of the study cancer that would result in overlap of&#xD;
             radiation therapy fields&#xD;
&#xD;
          -  Patients currently using metformin (metformin hydrochloride), other oral hypoglycemic&#xD;
             agents or insulin&#xD;
&#xD;
          -  Patients with any history of allergic reaction to paclitaxel or other taxanes or&#xD;
             carboplatin&#xD;
&#xD;
          -  Patients with a history of chronic kidney disease or lactic acidosis&#xD;
&#xD;
          -  Patients with &gt;= 10% weight loss within the past month&#xD;
&#xD;
          -  Severe, active co-morbidity, defined as follows:&#xD;
&#xD;
               -  Diagnosis of type I or type II diabetes mellitus&#xD;
&#xD;
               -  Uncontrolled neuropathy &gt;= grade 2 regardless of cause&#xD;
&#xD;
               -  Unstable angina and/or congestive heart failure requiring hospitalization within&#xD;
                  the last 6 months&#xD;
&#xD;
               -  Transmural myocardial infarction within the last 6 months&#xD;
&#xD;
               -  Acute bacterial or fungal infection requiring intravenous antibiotics at the time&#xD;
                  of registration&#xD;
&#xD;
               -  Chronic obstructive pulmonary disease exacerbation or other respiratory illness&#xD;
                  requiring hospitalization or precluding study therapy within 30 days of&#xD;
                  registration&#xD;
&#xD;
               -  Severe hepatic disease, defined as a diagnosis of Child-Pugh class B or C hepatic&#xD;
                  disease&#xD;
&#xD;
               -  Human immunodeficiency virus (HIV) positive with cluster of differentiation (CD)4&#xD;
                  count &lt; 200 cells/microliter; note that patients who are HIV positive are&#xD;
                  eligible, provided they are under treatment with highly active antiretroviral&#xD;
                  therapy (HAART) and have a CD4 count &gt;= 200 cells/microliter within 30 days prior&#xD;
                  to registration; note also that HIV testing is not required for eligibility for&#xD;
                  this protocol&#xD;
&#xD;
               -  End-stage renal disease (ie, on dialysis or dialysis has been recommended)&#xD;
&#xD;
          -  Pregnancy or women of childbearing potential and men who are sexually active and not&#xD;
             willing/able to use medically acceptable forms of contraception&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Theodoros Tsakiridis</last_name>
    <role>Principal Investigator</role>
    <affiliation>NRG Oncology</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Lewis and Faye Manderson Cancer Center</name>
      <address>
        <city>Tuscaloosa</city>
        <state>Alabama</state>
        <zip>35401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Banner University Medical Center - Tucson</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85719</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sutter Cancer Centers Radiation Oncology Services-Auburn</name>
      <address>
        <city>Auburn</city>
        <state>California</state>
        <zip>95603</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sutter Cancer Centers Radiation Oncology Services-Cameron Park</name>
      <address>
        <city>Cameron Park</city>
        <state>California</state>
        <zip>95682</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Eden Hospital Medical Center</name>
      <address>
        <city>Castro Valley</city>
        <state>California</state>
        <zip>94546</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UC San Diego Moores Cancer Center</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92093</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Medical Center</name>
      <address>
        <city>Modesto</city>
        <state>California</state>
        <zip>95355</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente Oakland-Broadway</name>
      <address>
        <city>Oakland</city>
        <state>California</state>
        <zip>94611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente-Rancho Cordova Cancer Center</name>
      <address>
        <city>Rancho Cordova</city>
        <state>California</state>
        <zip>95670</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rohnert Park Cancer Center</name>
      <address>
        <city>Rohnert Park</city>
        <state>California</state>
        <zip>94928</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sutter Cancer Centers Radiation Oncology Services-Roseville</name>
      <address>
        <city>Roseville</city>
        <state>California</state>
        <zip>95661</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Permanente Medical Group-Roseville Radiation Oncology</name>
      <address>
        <city>Roseville</city>
        <state>California</state>
        <zip>95678</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sutter Medical Center Sacramento</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95816</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>South Sacramento Cancer Center</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95823</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UCSF Medical Center-Mount Zion</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente Cancer Treatment Center</name>
      <address>
        <city>South San Francisco</city>
        <state>California</state>
        <zip>94080</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sutter Cancer Centers Radiation Oncology Services-Vacaville</name>
      <address>
        <city>Vacaville</city>
        <state>California</state>
        <zip>95687</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Colorado Hospital</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Penrose-Saint Francis Healthcare</name>
      <address>
        <city>Colorado Springs</city>
        <state>Colorado</state>
        <zip>80907</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UCHealth Memorial Hospital Central</name>
      <address>
        <city>Colorado Springs</city>
        <state>Colorado</state>
        <zip>80909</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Swedish Medical Center</name>
      <address>
        <city>Englewood</city>
        <state>Colorado</state>
        <zip>80113</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>North Colorado Medical Center</name>
      <address>
        <city>Greeley</city>
        <state>Colorado</state>
        <zip>80631</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>McKee Medical Center</name>
      <address>
        <city>Loveland</city>
        <state>Colorado</state>
        <zip>80539</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SCL Health Lutheran Medical Center</name>
      <address>
        <city>Wheat Ridge</city>
        <state>Colorado</state>
        <zip>80033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Christiana Care Health System-Christiana Hospital</name>
      <address>
        <city>Newark</city>
        <state>Delaware</state>
        <zip>19718</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UF Cancer Center at Orlando Health</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>21st Century Oncology-Palatka</name>
      <address>
        <city>Palatka</city>
        <state>Florida</state>
        <zip>32177</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Piedmont Hospital</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30309</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>John B Amos Cancer Center</name>
      <address>
        <city>Columbus</city>
        <state>Georgia</state>
        <zip>31904</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dekalb Medical Center</name>
      <address>
        <city>Decatur</city>
        <state>Georgia</state>
        <zip>30033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Health University Medical Center</name>
      <address>
        <city>Savannah</city>
        <state>Georgia</state>
        <zip>31404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lewis Cancer and Research Pavilion at Saint Joseph's/Candler</name>
      <address>
        <city>Savannah</city>
        <state>Georgia</state>
        <zip>31405</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Cancer Center of Hawaii-Pali Momi</name>
      <address>
        <city>'Aiea</city>
        <state>Hawaii</state>
        <zip>96701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Queen's Medical Center</name>
      <address>
        <city>Honolulu</city>
        <state>Hawaii</state>
        <zip>96813</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Cancer Center of Hawaii-Liliha</name>
      <address>
        <city>Honolulu</city>
        <state>Hawaii</state>
        <zip>96817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Alphonsus Cancer Care Center-Boise</name>
      <address>
        <city>Boise</city>
        <state>Idaho</state>
        <zip>83706</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kootenai Cancer Center</name>
      <address>
        <city>Post Falls</city>
        <state>Idaho</state>
        <zip>83854</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Luke's Mountain States Tumor Institute-Twin Falls</name>
      <address>
        <city>Twin Falls</city>
        <state>Idaho</state>
        <zip>83301</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwest Community Hospital</name>
      <address>
        <city>Arlington Heights</city>
        <state>Illinois</state>
        <zip>60005</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>John H Stroger Jr Hospital of Cook County</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rush University Medical Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Decatur Memorial Hospital</name>
      <address>
        <city>Decatur</city>
        <state>Illinois</state>
        <zip>62526</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Good Samaritan Regional Health Center</name>
      <address>
        <city>Mount Vernon</city>
        <state>Illinois</state>
        <zip>62864</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center</name>
      <address>
        <city>Pekin</city>
        <state>Illinois</state>
        <zip>61554</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>OSF Saint Francis Radiation Oncology at Peoria Cancer Center</name>
      <address>
        <city>Peoria</city>
        <state>Illinois</state>
        <zip>61615</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Methodist Medical Center of Illinois</name>
      <address>
        <city>Peoria</city>
        <state>Illinois</state>
        <zip>61636</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>OSF Saint Francis Medical Center</name>
      <address>
        <city>Peoria</city>
        <state>Illinois</state>
        <zip>61637</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Medical Center</name>
      <address>
        <city>Springfield</city>
        <state>Illinois</state>
        <zip>62781</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Carle Cancer Center</name>
      <address>
        <city>Urbana</city>
        <state>Illinois</state>
        <zip>61801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IU Health Bloomington</name>
      <address>
        <city>Bloomington</city>
        <state>Indiana</state>
        <zip>47403</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Radiation Oncology Associates PC</name>
      <address>
        <city>Fort Wayne</city>
        <state>Indiana</state>
        <zip>46804</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Parkview Hospital Randallia</name>
      <address>
        <city>Fort Wayne</city>
        <state>Indiana</state>
        <zip>46805</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Franciscan Health Indianapolis</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46237</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mercy Hospital</name>
      <address>
        <city>Cedar Rapids</city>
        <state>Iowa</state>
        <zip>52403</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kansas Cancer Center</name>
      <address>
        <city>Kansas City</city>
        <state>Kansas</state>
        <zip>66160</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lawrence Memorial Hospital</name>
      <address>
        <city>Lawrence</city>
        <state>Kansas</state>
        <zip>66044</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kansas Cancer Center-Overland Park</name>
      <address>
        <city>Overland Park</city>
        <state>Kansas</state>
        <zip>66210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ascension Via Christi Hospitals Wichita</name>
      <address>
        <city>Wichita</city>
        <state>Kansas</state>
        <zip>67214</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wesley Medical Center</name>
      <address>
        <city>Wichita</city>
        <state>Kansas</state>
        <zip>67214</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hardin Memorial Hospital</name>
      <address>
        <city>Elizabethtown</city>
        <state>Kentucky</state>
        <zip>42701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baptist Health Lexington</name>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <zip>40503</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kentucky/Markey Cancer Center</name>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <zip>40536</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>LSU Health Baton Rouge-North Clinic</name>
      <address>
        <city>Baton Rouge</city>
        <state>Louisiana</state>
        <zip>70805</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Louisiana Hematology Oncology Associates LLC</name>
      <address>
        <city>Baton Rouge</city>
        <state>Louisiana</state>
        <zip>70809</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mary Bird Perkins Cancer Center</name>
      <address>
        <city>Baton Rouge</city>
        <state>Louisiana</state>
        <zip>70809</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Our Lady of the Lake Physicians Group - Medical Oncology</name>
      <address>
        <city>Baton Rouge</city>
        <state>Louisiana</state>
        <zip>70809</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mary Bird Perkins Cancer Center - Covington</name>
      <address>
        <city>Covington</city>
        <state>Louisiana</state>
        <zip>70433</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mary Bird Perkins Cancer Center - Houma</name>
      <address>
        <city>Houma</city>
        <state>Louisiana</state>
        <zip>70360</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Maine Medical Center- Scarborough Campus</name>
      <address>
        <city>Scarborough</city>
        <state>Maine</state>
        <zip>04074</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Maryland/Greenebaum Cancer Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UM Upper Chesapeake Medical Center</name>
      <address>
        <city>Bel Air</city>
        <state>Maryland</state>
        <zip>21014</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UM Baltimore Washington Medical Center/Tate Cancer Center</name>
      <address>
        <city>Glen Burnie</city>
        <state>Maryland</state>
        <zip>21061</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Peninsula Regional Medical Center</name>
      <address>
        <city>Salisbury</city>
        <state>Maryland</state>
        <zip>21801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Boston Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02118</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lowell General Hospital</name>
      <address>
        <city>Lowell</city>
        <state>Massachusetts</state>
        <zip>01854</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Henry Ford Hospital</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>McLaren Cancer Institute-Flint</name>
      <address>
        <city>Flint</city>
        <state>Michigan</state>
        <zip>48532</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mercy Health Saint Mary's</name>
      <address>
        <city>Grand Rapids</city>
        <state>Michigan</state>
        <zip>49503</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spectrum Health at Butterworth Campus</name>
      <address>
        <city>Grand Rapids</city>
        <state>Michigan</state>
        <zip>49503</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>West Michigan Cancer Center</name>
      <address>
        <city>Kalamazoo</city>
        <state>Michigan</state>
        <zip>49007</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>McLaren Cancer Institute-Lapeer Region</name>
      <address>
        <city>Lapeer</city>
        <state>Michigan</state>
        <zip>48446</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>McLaren Cancer Institute-Macomb</name>
      <address>
        <city>Mount Clemens</city>
        <state>Michigan</state>
        <zip>48043</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>McLaren Cancer Institute-Central Michigan</name>
      <address>
        <city>Mount Pleasant</city>
        <state>Michigan</state>
        <zip>48858</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mercy Health Mercy Campus</name>
      <address>
        <city>Muskegon</city>
        <state>Michigan</state>
        <zip>49444</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>McLaren Cancer Institute-Owosso</name>
      <address>
        <city>Owosso</city>
        <state>Michigan</state>
        <zip>48867</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>McLaren Cancer Institute-Northern Michigan</name>
      <address>
        <city>Petoskey</city>
        <state>Michigan</state>
        <zip>49770</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Joseph Mercy Oakland</name>
      <address>
        <city>Pontiac</city>
        <state>Michigan</state>
        <zip>48341</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>William Beaumont Hospital-Royal Oak</name>
      <address>
        <city>Royal Oak</city>
        <state>Michigan</state>
        <zip>48073</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lakeland Medical Center Saint Joseph</name>
      <address>
        <city>Saint Joseph</city>
        <state>Michigan</state>
        <zip>49085</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>William Beaumont Hospital - Troy</name>
      <address>
        <city>Troy</city>
        <state>Michigan</state>
        <zip>48085</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sanford Joe Lueken Cancer Center</name>
      <address>
        <city>Bemidji</city>
        <state>Minnesota</state>
        <zip>56601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mercy Hospital</name>
      <address>
        <city>Coon Rapids</city>
        <state>Minnesota</state>
        <zip>55433</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Luke's Hospital of Duluth</name>
      <address>
        <city>Duluth</city>
        <state>Minnesota</state>
        <zip>55805</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fairview-Southdale Hospital</name>
      <address>
        <city>Edina</city>
        <state>Minnesota</state>
        <zip>55435</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Abbott-Northwestern Hospital</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55407</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hennepin County Medical Center</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55415</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Regions Hospital</name>
      <address>
        <city>Saint Paul</city>
        <state>Minnesota</state>
        <zip>55101</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>United Hospital</name>
      <address>
        <city>Saint Paul</city>
        <state>Minnesota</state>
        <zip>55102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rice Memorial Hospital</name>
      <address>
        <city>Willmar</city>
        <state>Minnesota</state>
        <zip>56201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Mississippi Medical Center</name>
      <address>
        <city>Jackson</city>
        <state>Mississippi</state>
        <zip>39216</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Francis Medical Center</name>
      <address>
        <city>Cape Girardeau</city>
        <state>Missouri</state>
        <zip>63703</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southeast Cancer Center</name>
      <address>
        <city>Cape Girardeau</city>
        <state>Missouri</state>
        <zip>63703</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>North Kansas City Hospital</name>
      <address>
        <city>Kansas City</city>
        <state>Missouri</state>
        <zip>64116</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The University of Kansas Cancer Center-South</name>
      <address>
        <city>Kansas City</city>
        <state>Missouri</state>
        <zip>64131</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The University of Kansas Cancer Center-North</name>
      <address>
        <city>Kansas City</city>
        <state>Missouri</state>
        <zip>64154</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The University of Kansas Cancer Center-Lee's Summit</name>
      <address>
        <city>Lee's Summit</city>
        <state>Missouri</state>
        <zip>64064</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Delbert Day Cancer Institute at PCRMC</name>
      <address>
        <city>Rolla</city>
        <state>Missouri</state>
        <zip>65401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Missouri Baptist Medical Center</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63131</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mercy Hospital Saint Louis</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63141</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CoxHealth South Hospital</name>
      <address>
        <city>Springfield</city>
        <state>Missouri</state>
        <zip>65807</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Billings Clinic Cancer Center</name>
      <address>
        <city>Billings</city>
        <state>Montana</state>
        <zip>59101</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Community Medical Hospital</name>
      <address>
        <city>Missoula</city>
        <state>Montana</state>
        <zip>59804</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHI Health Saint Francis</name>
      <address>
        <city>Grand Island</city>
        <state>Nebraska</state>
        <zip>68803</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHI Health Good Samaritan</name>
      <address>
        <city>Kearney</city>
        <state>Nebraska</state>
        <zip>68847</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nebraska Methodist Hospital</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Nebraska Medical Center</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68198</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wentworth-Douglass Hospital</name>
      <address>
        <city>Dover</city>
        <state>New Hampshire</state>
        <zip>03820</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dartmouth Hitchcock Medical Center</name>
      <address>
        <city>Lebanon</city>
        <state>New Hampshire</state>
        <zip>03756</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Virtua Memorial</name>
      <address>
        <city>Mount Holly</city>
        <state>New Jersey</state>
        <zip>08060</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Community Medical Center</name>
      <address>
        <city>Toms River</city>
        <state>New Jersey</state>
        <zip>08755</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Virtua Voorhees</name>
      <address>
        <city>Voorhees</city>
        <state>New Jersey</state>
        <zip>08043</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of New Mexico Cancer Center</name>
      <address>
        <city>Albuquerque</city>
        <state>New Mexico</state>
        <zip>87102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New Mexico Oncology Hematology Consultants</name>
      <address>
        <city>Albuquerque</city>
        <state>New Mexico</state>
        <zip>87109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New York-Presbyterian/Brooklyn Methodist Hospital</name>
      <address>
        <city>Brooklyn</city>
        <state>New York</state>
        <zip>11215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Rochester</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14642</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gaston Hematology and Oncology Associates-Belmont</name>
      <address>
        <city>Belmont</city>
        <state>North Carolina</state>
        <zip>28012</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CaroMont Regional Medical Center</name>
      <address>
        <city>Gastonia</city>
        <state>North Carolina</state>
        <zip>28054</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gaston Hematology and Oncology Associates</name>
      <address>
        <city>Gastonia</city>
        <state>North Carolina</state>
        <zip>28054</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>FirstHealth of the Carolinas-Moore Regional Hospital</name>
      <address>
        <city>Pinehurst</city>
        <state>North Carolina</state>
        <zip>28374</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sanford Bismarck Medical Center</name>
      <address>
        <city>Bismarck</city>
        <state>North Dakota</state>
        <zip>58501</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sanford Roger Maris Cancer Center</name>
      <address>
        <city>Fargo</city>
        <state>North Dakota</state>
        <zip>58122</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UHHS-Chagrin Highlands Medical Center</name>
      <address>
        <city>Beachwood</city>
        <state>Ohio</state>
        <zip>44122</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mercy Medical Center</name>
      <address>
        <city>Canton</city>
        <state>Ohio</state>
        <zip>44708</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aultman Health Foundation</name>
      <address>
        <city>Canton</city>
        <state>Ohio</state>
        <zip>44710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Geauga Hospital</name>
      <address>
        <city>Chardon</city>
        <state>Ohio</state>
        <zip>44024</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Adena Regional Medical Center</name>
      <address>
        <city>Chillicothe</city>
        <state>Ohio</state>
        <zip>45601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Cincinnati/Barrett Cancer Center</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45219</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Case Western Reserve University</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic Cancer Center/Fairview Hospital</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic Foundation</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ohio State University Comprehensive Cancer Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Riverside Methodist Hospital</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43214</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Mark H Zangmeister Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43219</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mount Carmel Health Center West</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43222</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Good Samaritan Hospital - Dayton</name>
      <address>
        <city>Dayton</city>
        <state>Ohio</state>
        <zip>45406</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mercy Cancer Center-Elyria</name>
      <address>
        <city>Elyria</city>
        <state>Ohio</state>
        <zip>44035</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic Cancer Center Independence</name>
      <address>
        <city>Independence</city>
        <state>Ohio</state>
        <zip>44131</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kettering Medical Center</name>
      <address>
        <city>Kettering</city>
        <state>Ohio</state>
        <zip>45429</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hillcrest Hospital Cancer Center</name>
      <address>
        <city>Mayfield Heights</city>
        <state>Ohio</state>
        <zip>44124</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UH Seidman Cancer Center at Lake Health Mentor Campus</name>
      <address>
        <city>Mentor</city>
        <state>Ohio</state>
        <zip>44060</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UH Seidman Cancer Center at Southwest General Hospital</name>
      <address>
        <city>Middleburg Heights</city>
        <state>Ohio</state>
        <zip>44130</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Newark Radiation Oncology</name>
      <address>
        <city>Newark</city>
        <state>Ohio</state>
        <zip>43055</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospitals Parma Medical Center</name>
      <address>
        <city>Parma</city>
        <state>Ohio</state>
        <zip>44129</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southern Ohio Medical Center</name>
      <address>
        <city>Portsmouth</city>
        <state>Ohio</state>
        <zip>45662</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>North Coast Cancer Care</name>
      <address>
        <city>Sandusky</city>
        <state>Ohio</state>
        <zip>44870</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UH Seidman Cancer Center at Firelands Regional Medical Center</name>
      <address>
        <city>Sandusky</city>
        <state>Ohio</state>
        <zip>44870</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic Cancer Center Strongsville</name>
      <address>
        <city>Strongsville</city>
        <state>Ohio</state>
        <zip>44136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Pointe</name>
      <address>
        <city>West Chester</city>
        <state>Ohio</state>
        <zip>45069</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UHHS-Westlake Medical Center</name>
      <address>
        <city>Westlake</city>
        <state>Ohio</state>
        <zip>44145</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic Wooster Family Health and Surgery Center</name>
      <address>
        <city>Wooster</city>
        <state>Ohio</state>
        <zip>44691</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Genesis Healthcare System Cancer Care Center</name>
      <address>
        <city>Zanesville</city>
        <state>Ohio</state>
        <zip>43701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Oklahoma Health Sciences Center</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Abington Memorial Hospital</name>
      <address>
        <city>Abington</city>
        <state>Pennsylvania</state>
        <zip>19001</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Geisinger Medical Center</name>
      <address>
        <city>Danville</city>
        <state>Pennsylvania</state>
        <zip>17822</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northeast Radiation Oncology Center</name>
      <address>
        <city>Dunmore</city>
        <state>Pennsylvania</state>
        <zip>18512</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Regional Cancer Center</name>
      <address>
        <city>Erie</city>
        <state>Pennsylvania</state>
        <zip>16505</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Thomas Jefferson University Hospital</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC-Shadyside Hospital</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Reading Hospital</name>
      <address>
        <city>West Reading</city>
        <state>Pennsylvania</state>
        <zip>19611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Geisinger Wyoming Valley/Henry Cancer Center</name>
      <address>
        <city>Wilkes-Barre</city>
        <state>Pennsylvania</state>
        <zip>18711</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lankenau Medical Center</name>
      <address>
        <city>Wynnewood</city>
        <state>Pennsylvania</state>
        <zip>19096</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AnMed Health Cancer Center</name>
      <address>
        <city>Anderson</city>
        <state>South Carolina</state>
        <zip>29621</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Greenville Health System Cancer Institute-Faris</name>
      <address>
        <city>Greenville</city>
        <state>South Carolina</state>
        <zip>29605</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Francis Cancer Center</name>
      <address>
        <city>Greenville</city>
        <state>South Carolina</state>
        <zip>29607</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Greenville Health System Cancer Institute-Eastside</name>
      <address>
        <city>Greenville</city>
        <state>South Carolina</state>
        <zip>29615</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Self Regional Healthcare</name>
      <address>
        <city>Greenwood</city>
        <state>South Carolina</state>
        <zip>29646</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Greenville Health System Cancer Institute-Greer</name>
      <address>
        <city>Greer</city>
        <state>South Carolina</state>
        <zip>29650</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gibbs Cancer Center-Pelham</name>
      <address>
        <city>Greer</city>
        <state>South Carolina</state>
        <zip>29651</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Greenville Health System Cancer Institute-Seneca</name>
      <address>
        <city>Seneca</city>
        <state>South Carolina</state>
        <zip>29672</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spartanburg Medical Center</name>
      <address>
        <city>Spartanburg</city>
        <state>South Carolina</state>
        <zip>29303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Greenville Health System Cancer Institute-Spartanburg</name>
      <address>
        <city>Spartanburg</city>
        <state>South Carolina</state>
        <zip>29307</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sanford USD Medical Center - Sioux Falls</name>
      <address>
        <city>Sioux Falls</city>
        <state>South Dakota</state>
        <zip>57117-5134</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas Medical Branch</name>
      <address>
        <city>Galveston</city>
        <state>Texas</state>
        <zip>77555-0565</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>M D Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Methodist Hospital System</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MD Anderson in Katy</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77094</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UTMB Cancer Center at Victory Lakes</name>
      <address>
        <city>League City</city>
        <state>Texas</state>
        <zip>77573</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MD Anderson League City</name>
      <address>
        <city>Nassau Bay</city>
        <state>Texas</state>
        <zip>77058</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MD Anderson in Sugar Land</name>
      <address>
        <city>Sugar Land</city>
        <state>Texas</state>
        <zip>77478</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MD Anderson in The Woodlands</name>
      <address>
        <city>The Woodlands</city>
        <state>Texas</state>
        <zip>77384</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Intermountain Medical Center</name>
      <address>
        <city>Murray</city>
        <state>Utah</state>
        <zip>84107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Central Vermont Medical Center/National Life Cancer Treatment</name>
      <address>
        <city>Berlin</city>
        <state>Vermont</state>
        <zip>05602</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Vermont Medical Center</name>
      <address>
        <city>Burlington</city>
        <state>Vermont</state>
        <zip>05401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Norris Cotton Cancer Center-North</name>
      <address>
        <city>Saint Johnsbury</city>
        <state>Vermont</state>
        <zip>05819</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Augusta Health Center for Cancer and Blood Disorders</name>
      <address>
        <city>Fishersville</city>
        <state>Virginia</state>
        <zip>22939</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Harrison Medical Center</name>
      <address>
        <city>Bremerton</city>
        <state>Washington</state>
        <zip>98310</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>PeaceHealth Saint John Medical Center</name>
      <address>
        <city>Longview</city>
        <state>Washington</state>
        <zip>98632</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>PeaceHealth Southwest Medical Center</name>
      <address>
        <city>Vancouver</city>
        <state>Washington</state>
        <zip>98664</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wheeling Hospital/Schiffler Cancer Center</name>
      <address>
        <city>Wheeling</city>
        <state>West Virginia</state>
        <zip>26003</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aurora Cancer Care-Grafton</name>
      <address>
        <city>Grafton</city>
        <state>Wisconsin</state>
        <zip>53024</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aurora BayCare Medical Center</name>
      <address>
        <city>Green Bay</city>
        <state>Wisconsin</state>
        <zip>54311</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aurora Cancer Care-Kenosha South</name>
      <address>
        <city>Kenosha</city>
        <state>Wisconsin</state>
        <zip>53142</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bay Area Medical Center</name>
      <address>
        <city>Marinette</city>
        <state>Wisconsin</state>
        <zip>54143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Marshfield Medical Center-Marshfield</name>
      <address>
        <city>Marshfield</city>
        <state>Wisconsin</state>
        <zip>54449</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Community Memorial Hospital</name>
      <address>
        <city>Menomonee Falls</city>
        <state>Wisconsin</state>
        <zip>53051</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ascension Columbia Saint Mary's Hospital Ozaukee</name>
      <address>
        <city>Mequon</city>
        <state>Wisconsin</state>
        <zip>53097</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ascension Columbia Saint Mary's Water Tower Medical Commons</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aurora Saint Luke's Medical Center</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical College of Wisconsin</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Zablocki Veterans Administration Medical Center</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53295</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Marshfield Clinic-Minocqua Center</name>
      <address>
        <city>Minocqua</city>
        <state>Wisconsin</state>
        <zip>54548</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Center of Western Wisconsin</name>
      <address>
        <city>New Richmond</city>
        <state>Wisconsin</state>
        <zip>54017</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Marshfield Medical Center-Rice Lake</name>
      <address>
        <city>Rice Lake</city>
        <state>Wisconsin</state>
        <zip>54868</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Michael's Hospital</name>
      <address>
        <city>Stevens Point</city>
        <state>Wisconsin</state>
        <zip>54481</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aurora Medical Center in Summit</name>
      <address>
        <city>Summit</city>
        <state>Wisconsin</state>
        <zip>53066</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vince Lombardi Cancer Clinic-Two Rivers</name>
      <address>
        <city>Two Rivers</city>
        <state>Wisconsin</state>
        <zip>54241</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aurora West Allis Medical Center</name>
      <address>
        <city>West Allis</city>
        <state>Wisconsin</state>
        <zip>53227</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Alyce and Elmore Kraemer Cancer Care Center</name>
      <address>
        <city>West Bend</city>
        <state>Wisconsin</state>
        <zip>53095</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Diagnostic and Treatment Center</name>
      <address>
        <city>Weston</city>
        <state>Wisconsin</state>
        <zip>54476</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aspirus UW Cancer Center</name>
      <address>
        <city>Wisconsin Rapids</city>
        <state>Wisconsin</state>
        <zip>54494</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jewish General Hospital</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H3T 1E2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Allan Blair Cancer Centre</name>
      <address>
        <city>Regina</city>
        <state>Saskatchewan</state>
        <zip>S4T 7T1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saskatoon Cancer Centre</name>
      <address>
        <city>Saskatoon</city>
        <state>Saskatchewan</state>
        <zip>S7N 4H4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chaim Sheba Medical Center</name>
      <address>
        <city>Tel Hashomer</city>
        <zip>52621</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>Israel</country>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>July 8, 2014</study_first_submitted>
  <study_first_submitted_qc>July 8, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 10, 2014</study_first_posted>
  <results_first_submitted>May 18, 2020</results_first_submitted>
  <results_first_submitted_qc>June 10, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">June 23, 2020</results_first_posted>
  <last_update_submitted>June 16, 2023</last_update_submitted>
  <last_update_submitted_qc>June 16, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 22, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Lung Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
    <mesh_term>Adenocarcinoma of Lung</mesh_term>
    <mesh_term>Adenocarcinoma, Bronchiolo-Alveolar</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metformin</mesh_term>
    <mesh_term>Paclitaxel</mesh_term>
    <mesh_term>Carboplatin</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 1, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/47/NCT02186847/Prot_SAP_001.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>November 1, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/47/NCT02186847/ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Chemoradiation</title>
          <description>60 Gy Radiation therapy with concurrent paclitaxel and carboplatin followed by consolidation paclitaxel and carboplatin</description>
        </group>
        <group group_id="P2">
          <title>Metformin + Chemoradiation</title>
          <description>Metformin plus 60 Gy Radiation therapy with concurrent paclitaxel and carboplatin followed by consolidation paclitaxel and carboplatin</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="84"/>
                <participants group_id="P2" count="86"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Eligible Population</title>
              <participants_list>
                <participants group_id="P1" count="81"/>
                <participants group_id="P2" count="86"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Eligible and Started Protocol Treatment</title>
              <participants_list>
                <participants group_id="P1" count="76"/>
                <participants group_id="P2" count="82"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="81"/>
                <participants group_id="P2" count="86"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Eligible participants</population>
      <group_list>
        <group group_id="B1">
          <title>Chemoradiation</title>
          <description>60 Gy Radiation therapy with concurrent paclitaxel and carboplatin followed by consolidation paclitaxel and carboplatin</description>
        </group>
        <group group_id="B2">
          <title>Metformin + Chemoradiation</title>
          <description>Metformin plus 60 Gy Radiation therapy with concurrent paclitaxel and carboplatin followed by consolidation paclitaxel and carboplatin</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="81"/>
            <count group_id="B2" value="86"/>
            <count group_id="B3" value="167"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age, Customized</title>
          <description>years</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>≤ 49</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>50-59</title>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                    <measurement group_id="B2" value="26"/>
                    <measurement group_id="B3" value="48"/>
                  </measurement_list>
                </category>
                <category>
                  <title>60-69</title>
                  <measurement_list>
                    <measurement group_id="B1" value="29"/>
                    <measurement group_id="B2" value="35"/>
                    <measurement group_id="B3" value="64"/>
                  </measurement_list>
                </category>
                <category>
                  <title>≥ 70</title>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="22"/>
                    <measurement group_id="B3" value="46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="48"/>
                    <measurement group_id="B2" value="49"/>
                    <measurement group_id="B3" value="97"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="33"/>
                    <measurement group_id="B2" value="37"/>
                    <measurement group_id="B3" value="70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="77"/>
                    <measurement group_id="B2" value="80"/>
                    <measurement group_id="B3" value="157"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="67"/>
                    <measurement group_id="B2" value="70"/>
                    <measurement group_id="B3" value="137"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Zubrod performance status</title>
          <description>0 = Asymptomatic; 1 = Symptomatic but completely ambulatory; 2 = Symptomatic, &lt;50% in bed during the day; 3 = Symptomatic, &gt;50% in bed, but not bed bound; 4 = Bedbound; 5 = Death</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="38"/>
                    <measurement group_id="B2" value="45"/>
                    <measurement group_id="B3" value="83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="43"/>
                    <measurement group_id="B2" value="41"/>
                    <measurement group_id="B3" value="84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>American Joint Committee on Cancer (AJCC ) Stage, 7th edition</title>
          <description>Tumor stage refers to the size and/or extent of the main tumor. The higher the number after the T, the larger the tumor or the more it has grown into nearby tissues. T's may be further divided to provide more detail, such as T3a and T3b.TX=Primary tumor not visualized by imaging or bronchoscopy. Regional lymph nodes staging refers to the number and/or extent of spread of lymph nodes that contain cancer. The higher the number after the N, the greater the involvement of regional lymph nodes. M0=No distant metastasis</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>IIIA (M0:T1a-b,N2;T2a-b,N2;T3,N1-2;T4,N0-1)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="52"/>
                    <measurement group_id="B2" value="58"/>
                    <measurement group_id="B3" value="110"/>
                  </measurement_list>
                </category>
                <category>
                  <title>IIIB (M0: T1a-b,N3;T2a-b,N3;T3,N3;T4,N2-3)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="28"/>
                    <measurement group_id="B2" value="26"/>
                    <measurement group_id="B3" value="54"/>
                  </measurement_list>
                </category>
                <category>
                  <title>N2,TX, M0</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Histology</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Adenocarcinoma</title>
                  <measurement_list>
                    <measurement group_id="B1" value="31"/>
                    <measurement group_id="B2" value="42"/>
                    <measurement group_id="B3" value="73"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Adenosquamous</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Non-small cell lung cancer NOS</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Squamous cell carcinoma</title>
                  <measurement_list>
                    <measurement group_id="B1" value="38"/>
                    <measurement group_id="B2" value="35"/>
                    <measurement group_id="B3" value="73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Did the patient use cigarettes?</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>No</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Yes, but quit</title>
                  <measurement_list>
                    <measurement group_id="B1" value="47"/>
                    <measurement group_id="B2" value="52"/>
                    <measurement group_id="B3" value="99"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Yes, currently smokes</title>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="42"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants Alive Without Progression (Progression-free Survival)</title>
        <description>Progression is defined per RECIST v1.1 as change in a known lesion(s) meeting one of the following criteria: [1] At least a 20% increase in the sum of the longest diameter of target lesions such that the absolute increase must be &gt; 5 mm. [2] Appearance of ≥1 new lesions. Progression-free survival time is defined as time from randomization to the date of first progression, death, or last known follow-up (censored). Progression-free survival rates are estimated using the Kaplan-Meier method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. One-year rates are provided. Analysis occurred after 102 progression-free survival events were reported.</description>
        <time_frame>From randomization to last follow-up. Maximum follow-up at time of analysis was 47.2 months.</time_frame>
        <population>Eligible participants</population>
        <group_list>
          <group group_id="O1">
            <title>Chemoradiation</title>
            <description>60 Gy Radiation therapy with concurrent paclitaxel and carboplatin followed by consolidation paclitaxel and carboplatin</description>
          </group>
          <group group_id="O2">
            <title>Metformin + Chemoradiation</title>
            <description>Metformin plus 60 Gy Radiation therapy with concurrent paclitaxel and carboplatin followed by consolidation paclitaxel and carboplatin</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Alive Without Progression (Progression-free Survival)</title>
          <description>Progression is defined per RECIST v1.1 as change in a known lesion(s) meeting one of the following criteria: [1] At least a 20% increase in the sum of the longest diameter of target lesions such that the absolute increase must be &gt; 5 mm. [2] Appearance of ≥1 new lesions. Progression-free survival time is defined as time from randomization to the date of first progression, death, or last known follow-up (censored). Progression-free survival rates are estimated using the Kaplan-Meier method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. One-year rates are provided. Analysis occurred after 102 progression-free survival events were reported.</description>
          <population>Eligible participants</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="81"/>
                <count group_id="O2" value="86"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="60.4" lower_limit="48.5" upper_limit="70.4"/>
                    <measurement group_id="O2" value="51.3" lower_limit="39.8" upper_limit="61.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The study was powered to detect an improvement of the 1-year progression-free survival rate from 50% (no metformin) to 65% (metformin) or equivalently a hazard ratio (HR) of 0.622, at one-sided type 1 error of 0.1 and 85% power with at least 102 progression-free survival events.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.7563</p_value>
            <method>Log Rank</method>
            <method_desc>One-sided significance level = 0.10</method_desc>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.15</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.77</ci_lower_limit>
            <ci_upper_limit>1.73</ci_upper_limit>
            <estimate_desc>Reference level = Chemoradiation</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Alive (Overall Survival)</title>
        <description>Overall survival time is defined as time from randomization to the date of death from any cause or last known follow-up (censored). Overall survival rates are estimated using the Kaplan-Meier method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. One-year rates are provided. Analysis occurred after 102 progression-free survival events were reported.</description>
        <time_frame>From randomization to last follow-up. Maximum follow-up at time of analysis was 47.2 months.</time_frame>
        <population>Eligible participants</population>
        <group_list>
          <group group_id="O1">
            <title>Chemoradiation</title>
            <description>60 Gy Radiation therapy with concurrent paclitaxel and carboplatin followed by consolidation paclitaxel and carboplatin</description>
          </group>
          <group group_id="O2">
            <title>Metformin + Chemoradiation</title>
            <description>Metformin plus 60 Gy Radiation therapy with concurrent paclitaxel and carboplatin followed by consolidation paclitaxel and carboplatin</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Alive (Overall Survival)</title>
          <description>Overall survival time is defined as time from randomization to the date of death from any cause or last known follow-up (censored). Overall survival rates are estimated using the Kaplan-Meier method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. One-year rates are provided. Analysis occurred after 102 progression-free survival events were reported.</description>
          <population>Eligible participants</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="81"/>
                <count group_id="O2" value="86"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="38.5" lower_limit="26.3" upper_limit="NA">Not reached</measurement>
                    <measurement group_id="O2" value="40.1" lower_limit="27.9" upper_limit="NA">Not reached</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.8910</p_value>
            <method>Log Rank</method>
            <method_desc>Two-sided significance level = 0.05</method_desc>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.03</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.64</ci_lower_limit>
            <ci_upper_limit>1.68</ci_upper_limit>
            <estimate_desc>Reference level = Chemoradiation</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Local-regional Progression</title>
        <description>Local-regional progression (LRP) is defined as progression within the planned treatment volume (PTV) or outside the PTV but within the same lobe(s) of the lung as the primary tumor or in regional lymph nodes. Progression is defined as change in a known lesion(s) meeting one of the following criteria: [1] ≥ 20% increase in the sum of the longest diameter of target lesions such that the absolute increase must be &gt; 5 mm. [2] Appearance of ≥1 new lesions. LRP time is defined as time from randomization to the date of first LRP, death without LRP (competing risk), or last known follow-up (censored). LRP rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. One-year rates are provided. Analysis occurred after 102 LRP events were reported.</description>
        <time_frame>From randomization to last follow-up. Maximum follow-up at time of analysis was 47.2 months.</time_frame>
        <population>Eligible participants</population>
        <group_list>
          <group group_id="O1">
            <title>Chemoradiation</title>
            <description>60 Gy Radiation therapy with concurrent paclitaxel and carboplatin followed by consolidation paclitaxel and carboplatin</description>
          </group>
          <group group_id="O2">
            <title>Metformin + Chemoradiation</title>
            <description>Metformin plus 60 Gy Radiation therapy with concurrent paclitaxel and carboplatin followed by consolidation paclitaxel and carboplatin</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Local-regional Progression</title>
          <description>Local-regional progression (LRP) is defined as progression within the planned treatment volume (PTV) or outside the PTV but within the same lobe(s) of the lung as the primary tumor or in regional lymph nodes. Progression is defined as change in a known lesion(s) meeting one of the following criteria: [1] ≥ 20% increase in the sum of the longest diameter of target lesions such that the absolute increase must be &gt; 5 mm. [2] Appearance of ≥1 new lesions. LRP time is defined as time from randomization to the date of first LRP, death without LRP (competing risk), or last known follow-up (censored). LRP rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. One-year rates are provided. Analysis occurred after 102 LRP events were reported.</description>
          <population>Eligible participants</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="81"/>
                <count group_id="O2" value="86"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.2" lower_limit="9.7" upper_limit="26.6"/>
                    <measurement group_id="O2" value="20.5" lower_limit="12.4" upper_limit="30.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.4075</p_value>
            <method>Log Rank</method>
            <method_desc>Two-side significance level = 0.05</method_desc>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.29</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.71</ci_lower_limit>
            <ci_upper_limit>2.34</ci_upper_limit>
            <estimate_desc>Reference level = Chemoradiation</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Distant Metastases</title>
        <description>Distant metastasis (DM) is defined as the appearance of ≥ 1 new lesions at any site (including pleural or pericardial effusion) outside of the following: the planned treatment volume, the same lobe(s) of the lung as the primary tumor, or regional lymph nodes. Time to DM is defined as time from randomization to the date of first DM, death without DM (competing risk), or last known follow-up (censored). DM rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. One-year rates are provided. Analysis occurred after 102 progression-free survival events were reported.</description>
        <time_frame>From randomization to last follow-up. Maximum follow-up at time of analysis was 47.2 months.</time_frame>
        <population>Eligible participants</population>
        <group_list>
          <group group_id="O1">
            <title>Chemoradiation</title>
            <description>60 Gy Radiation therapy with concurrent paclitaxel and carboplatin followed by consolidation paclitaxel and carboplatin</description>
          </group>
          <group group_id="O2">
            <title>Metformin + Chemoradiation</title>
            <description>Metformin plus 60 Gy Radiation therapy with concurrent paclitaxel and carboplatin followed by consolidation paclitaxel and carboplatin</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Distant Metastases</title>
          <description>Distant metastasis (DM) is defined as the appearance of ≥ 1 new lesions at any site (including pleural or pericardial effusion) outside of the following: the planned treatment volume, the same lobe(s) of the lung as the primary tumor, or regional lymph nodes. Time to DM is defined as time from randomization to the date of first DM, death without DM (competing risk), or last known follow-up (censored). DM rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. One-year rates are provided. Analysis occurred after 102 progression-free survival events were reported.</description>
          <population>Eligible participants</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="81"/>
                <count group_id="O2" value="86"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.2" lower_limit="9.7" upper_limit="26.6"/>
                    <measurement group_id="O2" value="20.5" lower_limit="12.4" upper_limit="30.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.4075</p_value>
            <method>Log Rank</method>
            <method_desc>Two-sided significance level = 0.05</method_desc>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.29</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.71</ci_lower_limit>
            <ci_upper_limit>2.34</ci_upper_limit>
            <estimate_desc>Reference level = Chemoradiation</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Treatment-related Grade 3 or Higher Adverse Events</title>
        <description>Adverse events (AE) were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to adverse event. &quot;Treatment-related&quot; is defined definitely, probably, or possibly related to treatment.</description>
        <time_frame>From start of treatment to last follow-up. Maximum follow-up at time of analysis was 47.2 months.</time_frame>
        <population>Eligible participants who started protocol treatment</population>
        <group_list>
          <group group_id="O1">
            <title>Chemoradiation</title>
            <description>60 Gy Radiation therapy with concurrent paclitaxel and carboplatin followed by consolidation paclitaxel and carboplatin</description>
          </group>
          <group group_id="O2">
            <title>Metformin + Chemoradiation</title>
            <description>Metformin plus 60 Gy Radiation therapy with concurrent paclitaxel and carboplatin followed by consolidation paclitaxel and carboplatin</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Treatment-related Grade 3 or Higher Adverse Events</title>
          <description>Adverse events (AE) were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to adverse event. &quot;Treatment-related&quot; is defined definitely, probably, or possibly related to treatment.</description>
          <population>Eligible participants who started protocol treatment</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="76"/>
                <count group_id="O2" value="82"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="67.1" lower_limit="55.4" upper_limit="77.5"/>
                    <measurement group_id="O2" value="63.4" lower_limit="52.1" upper_limit="73.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.6266</p_value>
            <method>Chi-squared</method>
            <method_desc>Two-sided significance level = 0.05</method_desc>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>0.92</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.47</ci_lower_limit>
            <ci_upper_limit>1.80</ci_upper_limit>
            <estimate_desc>Reference level = Chemoradiation</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were to be reported weekly during dose escalation on metformin arm, end of chemoradiation, end of post-radiation chemotherapy/metformin, 4-6 weeks follow-up, every 3 months for 2 years follow-up, every 6 months through 5 years follow-up, yearly until study termination completion.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Chemoradiation</title>
          <description>60 Gy Radiation therapy with concurrent paclitaxel and carboplatin followed by consolidation paclitaxel and carboplatin</description>
        </group>
        <group group_id="E2">
          <title>Metformin + Chemoradiation</title>
          <description>Metformin plus 60 Gy Radiation therapy with concurrent paclitaxel and carboplatin followed by consolidation paclitaxel and carboplatin</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="31" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="34" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="31" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="27" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Atrial flutter</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Cardiac disorders - Other</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Heart failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Esophageal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Esophagitis</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Death NOS</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Infusion related reaction</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Endocarditis infective</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Esophageal infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Infections and infestations - Other</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Pleural infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Dermatitis radiation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Spinal fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Investigations - Other</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Hypercalcemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Generalized muscle weakness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Intracranial hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Peripheral motor neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Presyncope</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Reversible posterior leukoencephalopathy syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Seizure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Stroke</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Tremor</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Aspiration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Bronchopulmonary hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Respiratory, thoracic and mediastinal disorders - Other</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Thromboembolic event</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="75" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="79" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" subjects_affected="50" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="46" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Hearing impaired</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blurred vision</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="35" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="29" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="25" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="46" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" subjects_affected="31" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="29" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Esophageal pain</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Esophagitis</sub_title>
                <counts group_id="E1" subjects_affected="29" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="37" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Gastroesophageal reflux disease</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorders - Other</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="43" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="48" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="34" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Edema limbs</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="61" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="66" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="13" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Infusion related reaction</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Localized edema</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="21" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="21" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchial infection</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Infections and infestations - Other</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Upper respiratory infection</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Dermatitis radiation</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="19" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="35" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="32" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="21" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="31" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="36" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="37" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Weight gain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="30" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" subjects_affected="40" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="39" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="33" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="18" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="23" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Hypernatremia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" subjects_affected="25" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="21" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="16" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Hypomagnesemia</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="16" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="24" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Generalized muscle weakness</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="19" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Musculoskeletal and connective tissue disorder - Other</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="16" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="19" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="16" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="23" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Paresthesia</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Peripheral motor neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="31" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="35" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Confusion</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="13" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="45" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="40" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" subjects_affected="42" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="42" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Hiccups</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Hoarseness</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Pulmonary fibrosis</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Respiratory, thoracic and mediastinal disorders - Other</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Sore throat</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Wheezing</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="28" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="28" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders - Other</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hot flashes</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Thromboembolic event</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="76"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>PI's are required to abide by the sponsor's publication guidelines which require review by coauthors and subsequent review and approval by the sponsor.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Wendy Seiferheld</name_or_title>
      <organization>NRG Oncology</organization>
      <phone>215-574-3208</phone>
      <email>seiferheldw@nrgoncology.org</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02186847
org study id: NRG-LU001
secondary id: NCI-2014-01071
secondary id: PNRG-LU001_A01PAMDREVW01
secondary id: NRG-LU001
secondary id: NRG-LU001
secondary id: U10CA180868
nct id: NCT02186847
lead sponsor: 
collaborator: 
has dmc: Yes
This randomized phase II trial studies how well chemotherapy and radiation therapy given with
      or without metformin hydrochloride works in treating patients with stage III non-small cell
      lung cancer. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in
      different ways to stop the growth of tumor cells, either by killing the cells, by stopping
      them from dividing, or by stopping them from spreading. Radiation therapy uses high-energy
      x-rays to kill tumor cells and shrink tumors. Metformin hydrochloride may shrink tumors and
      keep them from coming back. It is not yet known whether chemotherapy and radiation therapy is
      more effective when given with or without metformin hydrochloride in treating stage III
      non-small cell lung cancer.
PRIMARY OBJECTIVES:

      I. To determine whether metformin hydrochloride (MET) added to chemoradiotherapy can improve
      progression-free survival (PFS) in patients with locally advanced non-small cell lung cancer
      (NSCLC).

      SECONDARY OBJECTIVES:

      I. Determine the effects of MET on overall survival (OS), time to local-regional progression
      (LRP), and time to distant metastasis (DM).

      II. Evaluate the effect of MET on chemoradiotherapy toxicity (Common Terminology Criteria for
      Adverse Events, version 4 [CTCAE, v. 4]) within 1 year of completion of all treatment.

      III. Collect biospecimens to develop biomarkers of MET activity.

      OUTLINE: Patients are randomized to 1 of 2 treatment arms.

      After completion of study treatment, patients are followed up at 4-6 weeks, every 3 months
      for 2 years, every 6 months for 3 years, and then annually thereafter.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Participants Alive Without Progression (Progression-free Survival)
time frame: From randomization to last follow-up. Maximum follow-up at time of analysis was 47.2 months.
description: Progression is defined per RECIST v1.1 as change in a known lesion(s) meeting one of the following criteria: [1] At least a 20% increase in the sum of the longest diameter of target lesions such that the absolute increase must be > 5 mm. [2] Appearance of ≥1 new lesions. Progression-free survival time is defined as time from randomization to the date of first progression, death, or last known follow-up (censored). Progression-free survival rates are estimated using the Kaplan-Meier method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. One-year rates are provided. Analysis occurred after 102 progression-free survival events were reported.
measure: Percentage of Participants Alive (Overall Survival)
time frame: From randomization to last follow-up. Maximum follow-up at time of analysis was 47.2 months.
description: Overall survival time is defined as time from randomization to the date of death from any cause or last known follow-up (censored). Overall survival rates are estimated using the Kaplan-Meier method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. One-year rates are provided. Analysis occurred after 102 progression-free survival events were reported.
measure: Percentage of Participants With Local-regional Progression
time frame: From randomization to last follow-up. Maximum follow-up at time of analysis was 47.2 months.
description: Local-regional progression (LRP) is defined as progression within the planned treatment volume (PTV) or outside the PTV but within the same lobe(s) of the lung as the primary tumor or in regional lymph nodes. Progression is defined as change in a known lesion(s) meeting one of the following criteria: [1] ≥ 20% increase in the sum of the longest diameter of target lesions such that the absolute increase must be > 5 mm. [2] Appearance of ≥1 new lesions. LRP time is defined as time from randomization to the date of first LRP, death without LRP (competing risk), or last known follow-up (censored). LRP rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. One-year rates are provided. Analysis occurred after 102 LRP events were reported.
measure: Percentage of Participants With Distant Metastases
time frame: From randomization to last follow-up. Maximum follow-up at time of analysis was 47.2 months.
description: Distant metastasis (DM) is defined as the appearance of ≥ 1 new lesions at any site (including pleural or pericardial effusion) outside of the following: the planned treatment volume, the same lobe(s) of the lung as the primary tumor, or regional lymph nodes. Time to DM is defined as time from randomization to the date of first DM, death without DM (competing risk), or last known follow-up (censored). DM rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. One-year rates are provided. Analysis occurred after 102 progression-free survival events were reported.
measure: Percentage of Participants With Treatment-related Grade 3 or Higher Adverse Events
time frame: From start of treatment to last follow-up. Maximum follow-up at time of analysis was 47.2 months.
description: Adverse events (AE) were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to adverse event. "Treatment-related" is defined definitely, probably, or possibly related to treatment.
arm group label: Chemoradiation
arm group type: Active Comparator
description: 60 Gy Radiation therapy with concurrent paclitaxel and carboplatin followed by consolidation paclitaxel and carboplatin
arm group label: Metformin + Chemoradiation
arm group type: Experimental
description: Metformin plus 60 Gy Radiation therapy with concurrent paclitaxel and carboplatin followed by consolidation paclitaxel and carboplatin
intervention type: Radiation
intervention name: Radiation Therapy
description: Radiation therapy (RT) is given in 2 Gy fractions once daily 5 days per week to a total of 30 fractions and 60 Gy. Photons required; 3-dimensional conformal radiation therapy (3D-CRT) or intensity-modulated radiation therapy (IMRT) permitted. Starts within 14 days of randomization (Chemoradiation arm) or 14 days after metformin starts (Chemoradiation + Metformin arm).
arm group label: Chemoradiation
arm group label: Metformin + Chemoradiation
other name: 3-dimensional conformal radiation therapy
other name: 3D-CRT
other name: Intensity-modulated radiation therapy
other name: IMRT
intervention type: Drug
intervention name: Carboplatin
description: 2 AUC (area under the curve) via IV weekly on days 1, 8, 15, 22, 29, and 36 from start of radiation therapy. Two 21 day cycles of 6 AUC via IV starting 28-42 days after the end of radiation therapy.
arm group label: Chemoradiation
arm group label: Metformin + Chemoradiation
intervention type: Drug
intervention name: Metformin
description: Metformin is taken orally. Dose escalation begins 2 weeks prior to the initiation of chemoradiation. 500 mg twice daily days 1-7 of metformin. 500 mg three times daily days 8-14 of metformin. Three times a day with the following dosage: 500mg in the morning, 1000mg at noon, and 500mg in the evening concurrent with chemoradiation and through consolidation chemotherapy (days 15-126 of metformin),
arm group label: Metformin + Chemoradiation
other name: Metformin HCL
other name: Metformin Hydrochloride
intervention type: Drug
intervention name: Paclitaxel
description: 50 mg/m2 via IV weekly on days 1, 8, 15, 22, 29, and 36 from start of radiation therapy. Two 21 day cycles of 200 mg/m2 via IV 28-42 days after the end of radiation therapy.
arm group label: Chemoradiation
arm group label: Metformin + Chemoradiation
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Theodoros Tsakiridis
role: Principal Investigator
affiliation: NRG Oncology
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country: Canada
country: Israel
country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Adenocarcinoma of Lung
mesh term: Adenocarcinoma, Bronchiolo-Alveolar
mesh term: Metformin
mesh term: Paclitaxel
mesh term: Carboplatin
provided document: 
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