<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/NCT03258554</url>
  </required_header>
  <id_info>
    <org_study_id>NCI-2017-01522</org_study_id>
    <secondary_id>NCI-2017-01522</secondary_id>
    <secondary_id>NRG-HN004</secondary_id>
    <secondary_id>NRG-HN004</secondary_id>
    <secondary_id>U10CA180868</secondary_id>
    <nct_id>NCT03258554</nct_id>
  </id_info>
  <brief_title>Radiation Therapy With Durvalumab or Cetuximab in Treating Patients With Locoregionally Advanced Head and Neck Cancer Who Cannot Take Cisplatin</brief_title>
  <official_title>Randomized Phase II/III Trial of Radiotherapy With Concurrent MEDI4736 (Durvalumab) vs. Radiotherapy With Concurrent Cetuximab in Patients With Locoregionally Advanced Head and Neck Cancer With a Contraindication to Cisplatin</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Canadian Cancer Trials Group</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>NRG Oncology</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>National Cancer Institute (NCI)</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase II/III trial studies how well radiation therapy works with durvalumab or cetuximab&#xD;
      in treating patients with head and neck cancer that has spread to a local and/or regional&#xD;
      area of the body who cannot take cisplatin. Radiation therapy uses high energy x-rays to kill&#xD;
      tumor cells and shrink tumors. Immunotherapy with monoclonal antibodies, such as durvalumab,&#xD;
      may help the body's immune system attack the cancer, and may interfere with the ability of&#xD;
      tumor cells to grow and spread. Cetuximab is a monoclonal antibody that may interfere with&#xD;
      the ability of tumor cells to grow and spread. It is not known if radiation therapy with&#xD;
      durvalumab will work better than the usual therapy of radiation therapy with cetuximab in&#xD;
      treating patients with head and neck cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To determine the safety of radiotherapy (RT) with concurrent and adjuvant anti-PD-L1&#xD;
      therapy (MEDI4736 [durvalumab]) is safe in patients with locoregionally advanced head and&#xD;
      neck cancer (HNC) who have a contraindication to cisplatin. (Lead-in) II. To test the&#xD;
      hypothesis that concurrent RT and anti-PD-L1 therapy improves progression free survival (PFS)&#xD;
      compared to standard therapy (RT with concurrent cetuximab) in patients with locoregionally&#xD;
      advanced HNC who have a contraindication to cisplatin. (Phase II) III. To test the hypothesis&#xD;
      that concurrent RT and anti-PD-L1 therapy improves overall survival compared to standard&#xD;
      therapy (RT with concurrent cetuximab) in patients with locoregionally advanced HNC who have&#xD;
      a contraindication to cisplatin. (Phase III)&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To compare toxicity using Common Terminology Criteria for Adverse Events (CTCAE) and&#xD;
      Patient Reported Outcomes (PRO)-CTCAE between patients treated with RT + anti-PD-L1 therapy&#xD;
      versus RT/cetuximab.&#xD;
&#xD;
      II. To test the effect of anti-PD-L1 therapy in the subpopulation of patients with tumors&#xD;
      that overexpress PD-L1.&#xD;
&#xD;
      III. To compare overall survival, response (at 4-month fludeoxyglucose F-18 [FDG]-positron&#xD;
      emission tomography [PET]-computed tomography [CT]), locoregional failure, distant&#xD;
      metastasis, and competing mortality in the two arms by known risk factors, including p16&#xD;
      status and omega score.&#xD;
&#xD;
      IV. To test the hypothesis that MEDI4736 (durvalumab) therapy arm will have less decline in&#xD;
      the physical function domain of European Organization for Research and Treatment of Cancer&#xD;
      Core Questionnaire (EORTC QLQ-C30 version 3.0) based on the change in score from baseline to&#xD;
      12 months from end of RT, compared to the cetuximab-RT arm in patients with locoregionally&#xD;
      advanced HNC who have a contraindication to cisplatin.&#xD;
&#xD;
      V. To test the hypothesis that MEDI4736 (durvalumab) therapy arm at 1 year (from end of RT)&#xD;
      will have less decline in swallowing related quality of life (QOL) using the M. D. Anderson&#xD;
      Dysphagia Inventory (MDADI) total composite score, based on the change in score from baseline&#xD;
      to 12 months from end of RT, compared to the cetuximab-RT arm in patients who are medically&#xD;
      unfit for cisplatin.&#xD;
&#xD;
      VI. To compare swallowing related performance and function short and long term using the&#xD;
      Performance Status Scale for Head &amp; Neck Cancer Patients (PSS-HN).&#xD;
&#xD;
      VII. To evaluate gastrostomy tube retention rates between arms.&#xD;
&#xD;
      EXPLORATORY OBJECTIVES:&#xD;
&#xD;
      I. To test the hypothesis that radiation combined with MEDI4736 (durvalumab) enhances the&#xD;
      adaptive immune response using three types of immunophenotyping compared to radiation&#xD;
      combined with cetuximab.&#xD;
&#xD;
      II. To compare overall QOL short term (end RT-8 months) and long term (12-24 months from end&#xD;
      of RT) between arms using the EORTC QLQ-C30 version 3.0/HN35.&#xD;
&#xD;
      III. To evaluate swallowing related QOL short term (end RT-8 months) and long term (12-24&#xD;
      months from end of RT) using the EORTC Head and Neck (HN)35 swallowing domain and MDADI&#xD;
      (subscales) between arms in patients with locoregionally advanced HNC who have a&#xD;
      contraindication to cisplatin.&#xD;
&#xD;
      IV. To evaluate patient reported fatigue using the fatigue items in the EORTC QLQ and&#xD;
      PRO-CTCAE.&#xD;
&#xD;
      V. To compare clinician and patient reported toxicity using CTCAE and PRO CTCAE.&#xD;
&#xD;
      VI. To explore health utilities between cetuximab and MEDI4736 (durvalumab) RT using the&#xD;
      European Quality of Life 5 Dimensional-5 Level (EQ5D-5L).&#xD;
&#xD;
      OUTLINE: Patients are randomized to 1 of 2 arms.&#xD;
&#xD;
      ARM I: Patients receive cetuximab intravenously (IV) weekly over 60-120 minutes. Treatment&#xD;
      repeats every week for up to 8 cycles in the absence of disease progression or unacceptable&#xD;
      toxicity. Beginning 5-7 days after first cetuximab dose, patients undergo intensity modulated&#xD;
      radiation therapy (IMRT) 5 fractions per week for up to 7 weeks.&#xD;
&#xD;
      ARM II: Patients receive durvalumab IV over 60 minutes every 4 weeks. Treatment repeats every&#xD;
      4 weeks for up to 7 cycles in the absence of disease progression or unacceptable toxicity.&#xD;
      Beginning week 2, patients undergo IMRT 5 fractions per week for up to 7 weeks.&#xD;
&#xD;
      After completion of study treatment, patients are followed up at 1 month, every 4 months for&#xD;
      1 year, every 6 months for 2 years, then annually thereafter.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">April 3, 2018</start_date>
  <completion_date type="Anticipated">June 28, 2024</completion_date>
  <primary_completion_date type="Actual">September 20, 2022</primary_completion_date>
  <phase>Phase 2/Phase 3</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>Dose-limiting toxicity (DLT) defined as the occurrence of an adverse event (AE) during the specified observation window (Lead -in)</measure>
    <time_frame>Up to 4 weeks after radiation therapy (RT)</time_frame>
    <description>AEs will be graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Progression-free survival (PFS) (Phase II)</measure>
    <time_frame>From randomization until first evidence of local, regional, or distant disease progression or recurrence, or death from any cause, assessed up to 3 years</time_frame>
    <description>PFS will be estimated using the Kaplan-Meier method. The difference in PFS between the two arms will be tested using a log-rank test.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Overall survival (OS) (Phase III)</measure>
    <time_frame>From randomization until death from any cause, assessed up to 3 years</time_frame>
    <description>OS will be estimated using the Kaplan-Meier method. The difference in OS between the two arms will be tested using a log-rank test. Exploratory analysis adjusting for important factors such as age, site, Zubrod performance status, and clinical stages will be conducted using Cox models.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Locoregional failure (LRF)</measure>
    <time_frame>From randomization until first evidence of local, regional disease progression or recurrence, or death from study cancer or unknown causes, assessed up to 3 years</time_frame>
    <description>LRF will be estimated by cumulative incidence methods and compared using a cause-specific log-rank test. All failure times will be measured from the date of study randomization to the date of failure or last follow up.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Distant metastasis (DM)</measure>
    <time_frame>From randomization until first evidence of distant metastasis, assessed up to 3 years</time_frame>
    <description>DM will be estimated by cumulative incidence methods and compared using a cause-specific log-rank test. All failure times will be measured from the date of study randomization to the date of failure or last follow up.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Competing mortality</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Will be estimated by cumulative incidence methods and the effects of other covariates will be assessed using the Generalized Competing Event Model for Cancer Risk model.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Response on 4-month fludeoxyglucose F-18 (FDG)-positron emission tomography (PET)/computed tomography (CT)</measure>
    <time_frame>Up to 4 months</time_frame>
    <description>Will be measured by Response Evaluation Criteria in Solid Tumors (RECIST). Response rates between the two arms will be compared using Fisher's exact test.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute toxicity</measure>
    <time_frame>Up to 180 days after the end of radiation therapy</time_frame>
    <description>The rates of adverse events will be estimated using a binomial distribution along with their associated 95% confidence intervals and will be compared using Fisher's exact test.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Late toxicity</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Late toxicities &gt; 180 days after the end of radiation therapy. The rates of adverse events will be estimated using a binomial distribution along with their associated 95% confidence intervals and will be compared using Fisher's exact test.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in quality of life (QOL) analysis</measure>
    <time_frame>Baseline up to 12 months</time_frame>
    <description>Assessed using European Organization for Research and Treatment of Cancer Core Questionnaire (EORTC QLQ)/Head-and-Neck module (H&amp;N35), EuroQol- 5 Dimension (EQ5D), M. D. Anderson Dysphagia Inventory (MDADI), patient reported outcomes (PRO)-CTCAE, geriatric screening (G8). The mean summary score of the EORTC QLQ/H&amp;N35, EQ5D, MDADI, PRO-CTCAE, G8, CCI, and the subscales will be determined. The mean change from baseline at each time point will be summarized using mean and standard deviations for each arm. Mean change from baseline will be compared between the arms using a two sample t test. If data normality assumptions are not met, the Wilcoxon rank sum test will be used to test the hypothesis. Mean change from baseline will be tested using an omnibus F test followed by individual comparisons of change scores at different time points within each treatment group. The same analysis will be conducted for between group comparisons at each time point.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in swallowing QOL using total composite M. D. Anderson Dysphagia Inventory (MDADI) score</measure>
    <time_frame>Baseline up to 1 year</time_frame>
    <description>The mean change from baseline at each time point will be summarized using mean and standard deviations for each arm. Mean change from baseline will be compared between the arms using a two sample t test. If data normality assumptions are not met, the Wilcoxon rank sum test will be used to test the hypothesis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Translational research, including PD-L1 and p16</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Analyses of interaction between treatment arm and marker status will be done. Additionally toxicity for the two arms by marker status will be compared. Univariable and multivariable analysis will be performed using the Cox proportional hazards model for OS. Potential covariates evaluated for the multivariate models would be assigned treatment, age, Zubrod performance status, T-stage, N-stage, primary site, smoking history, other risk factors, as well as p16 and/PD-L1.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Secondary biomarker analysis</measure>
    <time_frame>Baseline up to 4 months after RT</time_frame>
    <description>Will perform multiparametric flow cytometry on peripheral mononuclear cells (PBMC) from patient-derived blood samples to quantify changes in immune cell frequency and activation status before, during and after radiation combined with cetuximab or radiation combined with durvalumab. To assess the statistical significance of pre- to post-treatment changes in levels of immunoglobulin (Ig)Gs as well as other markers, normalized signal intensities (log2) will be tested using a paired t test within an arm and two sample t test between the two arms. If the distribution assumption is violated for the t tests, nonparametric tests, such as the Wilcoxon signed-rank test will be considered. Lastly, the association between PFS and OS and post-treatment changes in frequency and activation state of T-cells, clonality and diversity of T cell receptor (TCR), and IgG levels will be evaluated using a two-sided Wald test at 0.05 level on the basis of Cox models.</description>
  </other_outcome>
  <other_outcome>
    <measure>Patient Reported Outcomes-Common Terminology Criteria for Adverse Events (PRO-CTCAE)</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>PRO-CTCAE is not intended for expedited reporting, real time review or safety reporting. PRO-CTCAE data are exploratory and not currently intended for use in data safety monitoring or adverse event stopping rules.</description>
  </other_outcome>
  <other_outcome>
    <measure>QOL endpoints using other items in EORTC QLQ/HN35, EQ5D and MDADI subscales</measure>
    <time_frame>Up to 12-24 months from end of RT</time_frame>
    <description>The mean change from baseline at each time point will be summarized using mean and standard deviations for each arm. Mean change from baseline will be compared between the arms using a two sample t test. If data normality assumptions are not met, the Wilcoxon rank sum test will be used to test the hypothesis. Mean change from baseline will be tested using an omnibus F test followed by individual comparisons of change scores at different time points within each treatment group. The same analysis will be conducted for between group comparisons at each time point.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">189</enrollment>
  <condition>Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8</condition>
  <condition>Head and Neck Squamous Cell Carcinoma</condition>
  <condition>Hypopharyngeal Squamous Cell Carcinoma</condition>
  <condition>Laryngeal Squamous Cell Carcinoma</condition>
  <condition>Oral Cavity Squamous Cell Carcinoma</condition>
  <condition>Oropharyngeal Squamous Cell Carcinoma</condition>
  <condition>Pathologic Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8</condition>
  <condition>Squamous Cell Carcinoma of Unknown Primary</condition>
  <condition>Stage III Hypopharyngeal Carcinoma AJCC v8</condition>
  <condition>Stage III Laryngeal Cancer AJCC v8</condition>
  <condition>Stage III Lip and Oral Cavity Cancer AJCC v8</condition>
  <condition>Stage III Oropharyngeal (p16-Negative) Carcinoma AJCC v8</condition>
  <condition>Stage IVA Hypopharyngeal Carcinoma AJCC v8</condition>
  <condition>Stage IVA Laryngeal Cancer AJCC v8</condition>
  <condition>Stage IVA Lip and Oral Cavity Cancer AJCC v8</condition>
  <condition>Stage IVA Oropharyngeal (p16-Negative) Carcinoma AJCC v8</condition>
  <condition>Stage IVB Hypopharyngeal Carcinoma AJCC v8</condition>
  <condition>Stage IVB Laryngeal Cancer AJCC v8</condition>
  <condition>Stage IVB Lip and Oral Cavity Cancer AJCC v8</condition>
  <condition>Stage IVB Oropharyngeal (p16-Negative) Carcinoma AJCC v8</condition>
  <arm_group>
    <arm_group_label>Arm I (cetuximab, radiation therapy)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients receive cetuximab IV weekly over 60-120 minutes. Treatment repeats every week for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Beginning 5-7 days after first cetuximab dose, patients undergo IMRT 5 fractions per week for up to 7 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm II (durvalumab, radiation therapy)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive durvalumab IV over 60 minutes every 4 weeks. Treatment repeats every 4 weeks for up to 7 cycles in the absence of disease progression or unacceptable toxicity. Beginning week 2, patients undergo IMRT 5 fractions per week for up to 7 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Cetuximab</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm I (cetuximab, radiation therapy)</arm_group_label>
    <other_name>Cetuximab Biosimilar CDP-1</other_name>
    <other_name>Cetuximab Biosimilar CMAB009</other_name>
    <other_name>Cetuximab Biosimilar KL 140</other_name>
    <other_name>Chimeric Anti-EGFR Monoclonal Antibody</other_name>
    <other_name>Chimeric MoAb C225</other_name>
    <other_name>Chimeric Monoclonal Antibody C225</other_name>
    <other_name>Erbitux</other_name>
    <other_name>IMC-C225</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Durvalumab</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm II (durvalumab, radiation therapy)</arm_group_label>
    <other_name>Imfinzi</other_name>
    <other_name>Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer</other_name>
    <other_name>MEDI-4736</other_name>
    <other_name>MEDI4736</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Intensity-Modulated Radiation Therapy</intervention_name>
    <description>Undergo IMRT</description>
    <arm_group_label>Arm I (cetuximab, radiation therapy)</arm_group_label>
    <arm_group_label>Arm II (durvalumab, radiation therapy)</arm_group_label>
    <other_name>IMRT</other_name>
    <other_name>Intensity modulated radiation therapy (procedure)</other_name>
    <other_name>Intensity Modulated RT</other_name>
    <other_name>Intensity-Modulated Radiotherapy</other_name>
    <other_name>Radiation, Intensity-Modulated Radiotherapy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Arm I (cetuximab, radiation therapy)</arm_group_label>
    <arm_group_label>Arm II (durvalumab, radiation therapy)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Quality-of-Life Assessment</intervention_name>
    <description>Ancillary studies</description>
    <arm_group_label>Arm I (cetuximab, radiation therapy)</arm_group_label>
    <arm_group_label>Arm II (durvalumab, radiation therapy)</arm_group_label>
    <other_name>Quality of Life Assessment</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Questionnaire Administration</intervention_name>
    <description>Ancillary studies</description>
    <arm_group_label>Arm I (cetuximab, radiation therapy)</arm_group_label>
    <arm_group_label>Arm II (durvalumab, radiation therapy)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  PRIOR TO STEP 1 REGISTRATION INCLUSION CRITERIA&#xD;
&#xD;
          -  Patients must have pathologically confirmed, previously untreated, unresected squamous&#xD;
             cell carcinoma of the larynx, hypopharynx, oropharynx, oral cavity, or carcinoma of&#xD;
             unknown head/neck primary prior to step 1 registration; submission of hematoxylin and&#xD;
             eosin (H&amp;E) stained slides and formalin-fixed and paraffin-embedded (FFPE) tissue&#xD;
             block (or punch biopsy of FFPE block) to the biospecimen bank at University of&#xD;
             California, San Francisco (UCSF) for central review for oropharyngeal and unknown&#xD;
             primaries and for p16 analysis for all other non-oropharyngeal primaries is mandatory&#xD;
             for all patients; investigators should check with their pathology department regarding&#xD;
             release of biospecimens before approaching patients about participation in the trial;&#xD;
             for oropharyngeal and unknown primaries, submission of H&amp;E and p16 stained slides&#xD;
             (with the required block for PD-L1) to the biospecimen bank at UCSF for central review&#xD;
             is also required prior to step 2 registration&#xD;
&#xD;
               -  Note: fine needle aspirates (FNA) samples are not acceptable since they do not&#xD;
                  provide enough material for PD-L1 and p16 testing; however, if a cell block&#xD;
                  derived from the FNA is available, it is allowable if there are sufficient cells&#xD;
                  present in the block for PD-L1 testing; Dr. Jordan will determine this upon&#xD;
                  receipt; for sites submitting FNA cell blocks for ALL patients they must do so&#xD;
                  within 7-10 business days from registering the patient; sites must confirm with&#xD;
                  their cytology/pathology labs to make sure they can provide the required material&#xD;
                  as the bank must be able to retain these samples for the mandatory testing&#xD;
&#xD;
          -  Patients must have locoregionally advanced head and neck squamous cell carcinoma&#xD;
             (HNSCC)&#xD;
&#xD;
               -  For p16-positive oropharyngeal/unknown primaries, American Joint Committee on&#xD;
                  Cancer [AJCC] 8th edition stage III and selected stage I-II based on smoking&#xD;
                  status in pack-years&#xD;
&#xD;
               -  For laryngeal, hypopharyngeal, and oral cavity primaries and p16-negative&#xD;
                  oropharyngeal/unknown primaries, AJCC 8th edition stage III-IVB&#xD;
&#xD;
               -  Based on the following minimum diagnostic workup within 60 days prior to step 1&#xD;
                  registration:&#xD;
&#xD;
                    -  General history and physical examination by a radiation oncologist or&#xD;
                       medical oncologist or ear, nose and throat (ENT) or head &amp; neck surgeon&#xD;
&#xD;
                    -  For larynx, hypopharynx, and base of tongue primaries, a&#xD;
                       laryngopharyngoscopy (mirror and/or fiberoptic and/or direct procedure) is&#xD;
                       required, unless the patient cannot tolerate or refuses&#xD;
&#xD;
               -  Imaging of the head and neck with a neck CT or magnetic resonance imaging (MRI)&#xD;
                  (with contrast, unless contraindicated) or PET/CT; note that the CT portion of&#xD;
                  the PET/CT must be of diagnostic quality, including contrast administration&#xD;
                  unless contraindicated. If the CT portion of the PET/CT study is low-dose&#xD;
                  (non-diagnostic), then an additional CT or MRI study with contrast (unless&#xD;
                  contraindicated) is required&#xD;
&#xD;
               -  Chest imaging: chest CT with and without contrast (unless contraindicated) or&#xD;
                  PET/CT&#xD;
&#xD;
          -  Patients must have a contraindication to cisplatin as defined in the following bullet&#xD;
             points; sites must complete the online tool at comogram.org prior to step 1&#xD;
             registration to determine if the patient is eligible; the scores must be recorded on a&#xD;
             case report form (CRF)&#xD;
&#xD;
               -  Age &gt;= 70 with moderate to severe comorbidity or vulnerability to cisplatin,&#xD;
                  defined as having one or more of the following conditions within 30 days prior to&#xD;
                  step 1 registration:&#xD;
&#xD;
                    -  Modified Charlson Comorbidity Index &gt;= 1&#xD;
&#xD;
                    -  Adult Comorbidity Evaluation (ACE)-27 Index &gt;= 1&#xD;
&#xD;
                    -  Generalized Competing Event Model for Cancer Risk (GCE) omega PFS score &lt;&#xD;
                       0.80&#xD;
&#xD;
                    -  Geriatric screening (G-8) score =&lt; 14&#xD;
&#xD;
                    -  Cancer and Aging Research Group (CARG) toxicity score &gt;= 30%&#xD;
&#xD;
                    -  Cumulative Illness Rating scale for Geriatrics (CIRS-G) score &gt;= 4 OR&#xD;
&#xD;
               -  Age &lt; 70 with severe comorbidity or vulnerability to cisplatin, defined as having&#xD;
                  two or more of the following conditions within 30 days prior to step 1&#xD;
                  registration&#xD;
&#xD;
                    -  Modified Charlson Comorbidity Index &gt;= 1&#xD;
&#xD;
                    -  ACE-27 Index &gt;= 1&#xD;
&#xD;
                    -  GCE omega PFS-score &lt; 0.80&#xD;
&#xD;
                    -  G-8 score =&lt; 14&#xD;
&#xD;
                    -  CARG Toxicity score &gt;= 30%&#xD;
&#xD;
                    -  CIRS-G score &gt;= 4 OR&#xD;
&#xD;
               -  Age &gt;= 18 with an absolute or relative contraindication to cisplatin, defined as&#xD;
                  one or more of the following within 30 days prior to step 1 registration:&#xD;
&#xD;
                    -  Creatinine clearance (CC) &gt; 30 and &lt; 60 cc/min; for this calculation, use&#xD;
                       the Cockcroft-Gault formula&#xD;
&#xD;
                    -  Zubrod performance status 2 prior to step 1 registration&#xD;
&#xD;
                    -  Pre-existing peripheral neuropathy grade &gt;= 1&#xD;
&#xD;
                    -  History of hearing loss, defined as either:&#xD;
&#xD;
                         -  Existing need of a hearing aid OR&#xD;
&#xD;
                         -  &gt;= 25 decibel shift over 2 contiguous frequencies on a pretreatment&#xD;
                            hearing test as clinically indicated&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt;= 1,000 cells/mm^3 (within 14 days prior to step 1&#xD;
             registration)&#xD;
&#xD;
          -  Platelets &gt;= 100,000 cells/mm^3 (within 14 days prior to step 1 registration)&#xD;
&#xD;
          -  Hemoglobin &gt;= 9.0 g/dl (Note: the use of transfusion or other intervention to achieve&#xD;
             hemoglobin [Hgb] &gt;= 9.0 g/dl is acceptable) (within 14 days prior to step 1&#xD;
             registration)&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =&lt; 2.5 times&#xD;
             institutional upper limit of normal (within 14 days prior to step 1 registration)&#xD;
&#xD;
          -  Serum bilirubin =&lt; 1.5 x institutional upper limit of normal (within 14 days prior to&#xD;
             step 1 registration)&#xD;
&#xD;
          -  Measured creatinine clearance (CL) &gt; 30 mL/min or calculated creatinine CL &gt; 30 mL/min&#xD;
             by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine&#xD;
             collection for determination of creatinine clearance (within 14 days prior to step 1&#xD;
             registration)&#xD;
&#xD;
          -  For women of childbearing potential, a negative serum or urine pregnancy test within&#xD;
             14 days prior to step 1 registration; Note: women will be considered post-menopausal&#xD;
             if they have been amenorrheic for 12 months without an alternative medical cause; the&#xD;
             following age-specific requirements apply:&#xD;
&#xD;
               -  Women &lt; 50 years of age would be considered post-menopausal if they have been&#xD;
                  amenorrheic for 12 months or more following cessation of exogenous hormonal&#xD;
                  treatments and if they have luteinizing hormone and follicle-stimulating hormone&#xD;
                  levels in the post-menopausal range for the institution or underwent surgical&#xD;
                  sterilization (bilateral oophorectomy or hysterectomy)&#xD;
&#xD;
               -  Women &gt;= 50 years of age would be considered post-menopausal if they have been&#xD;
                  amenorrheic for 12 months or more following cessation of all exogenous hormonal&#xD;
                  treatments, had radiation-induced menopause with last menses &gt; 1 year ago, had&#xD;
                  chemotherapy-induced menopause with last menses &gt; 1 year ago, or underwent&#xD;
                  surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or&#xD;
                  hysterectomy)&#xD;
&#xD;
          -  The patient or a legally authorized representative must provide study-specific&#xD;
             informed consent prior to step 1 registration&#xD;
&#xD;
          -  PRIOR TO STEP 2 REGISTRATION INCLUSION CRITERIA&#xD;
&#xD;
          -  For patients with oropharyngeal or unknown primaries: p16 determination by&#xD;
             immunohistochemistry (defined as greater than 70% strong nuclear or nuclear and&#xD;
             cytoplasmic staining of tumor cells), confirmed by central pathology review&#xD;
&#xD;
               -  Note: for patients with oral cavity, laryngeal, and hypopharyngeal primaries,&#xD;
                  analysis of p16 status prior to step 2 registration/randomization is not required&#xD;
                  (p16 status will be analyzed centrally post-hoc); step 2 registration for these&#xD;
                  patients can be completed after step 1 registration&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  PRIOR TO STEP 1 REGISTRATION EXCLUSION CRITERIA&#xD;
&#xD;
          -  Prior invasive malignancy within the past 3 years (except for non-melanomatous skin&#xD;
             cancer, and early stage treated prostate cancer); synchronous head and neck primaries&#xD;
             are ineligible&#xD;
&#xD;
          -  Prior radiotherapy to the region of the study cancer that would result in overlap of&#xD;
             radiation therapy fields&#xD;
&#xD;
               -  Note: Prior external beam radiotherapy is excluded, but iodine 131 is allowed&#xD;
&#xD;
          -  Prior immunotherapy&#xD;
&#xD;
          -  Prior systemic therapy, including cytotoxic chemotherapy, biologic/targeted therapy,&#xD;
             or immune therapy for the study cancer&#xD;
&#xD;
          -  Major surgery within 28 days prior to step 1 registration&#xD;
&#xD;
          -  Proven evidence of distant metastases&#xD;
&#xD;
          -  If both of the following conditions are present, the patient is ineligible:&#xD;
&#xD;
               -  =&lt; 10 pack-year smoking history&#xD;
&#xD;
               -  p16-positive carcinoma of the oropharynx or unknown primary that are T0-3, N0-1&#xD;
                  (AJCC 8th Edition)&#xD;
&#xD;
                    -  Note: in the event that a registered patient with =&lt; 10 pack-years has a&#xD;
                       p16-positive result on central review with the tumor and nodal stage T0-3,&#xD;
                       N0-1 (AJCC 8th Edition), then the site will be notified that the patient is&#xD;
                       ineligible&#xD;
&#xD;
          -  Zubrod performance status &gt;= 3&#xD;
&#xD;
          -  Body weight =&lt; 30 kg&#xD;
&#xD;
          -  Patients with oral cavity cancer are excluded from participation if the patient is&#xD;
             medically operable and resection of the primary tumor is considered technically&#xD;
             feasible by an oral or head and neck cancers surgical subspecialist;(please consult&#xD;
             the surgical oncology co-principal investigator [PI], Steven Chang, Doctor of Medicine&#xD;
             [MD], if clarification is needed on an individual case)&#xD;
&#xD;
          -  Sodium &lt; 130 mmol/L or &gt; 155 mmol/L (within 14 days of step 1 registration, unless&#xD;
             corrected prior to step 1 registration)&#xD;
&#xD;
          -  Potassium &lt; 3.5 mmol/L or &gt; 6 mmol/L (within 14 days of step 1 registration, unless&#xD;
             corrected prior to step 1 registration)&#xD;
&#xD;
          -  Fasting glucose &lt; 40 mg/dl or &gt; 400 mg/dl (within 14 days of step 1 registration,&#xD;
             unless corrected prior to step 1 registration)&#xD;
&#xD;
          -  Serum calcium (ionized or adjusted for albumin) &lt; 7 mg/dl or &gt; 12.5 mg/dl (within 14&#xD;
             days of step 1 registration, unless corrected prior to step 1 registration)&#xD;
&#xD;
          -  Magnesium &lt; 0.9 mg/dl or &gt; 3 mg/dl (within 14 days of step 1 registration, unless&#xD;
             corrected prior to step 1 registration)&#xD;
&#xD;
          -  Unstable angina and/or congestive heart failure requiring hospitalization within 3&#xD;
             months prior to step 1 registration&#xD;
&#xD;
          -  Transmural myocardial infarction within 3 months prior to step 1 registration&#xD;
&#xD;
          -  Respiratory illness requiring hospitalization at the time of step 1 registration&#xD;
&#xD;
               -  Note: if the respiratory illness is resolved and the patient meets the&#xD;
                  eligibility status above, then the patient can be considered for the trial&#xD;
&#xD;
          -  Idiopathic pulmonary fibrosis or other severe interstitial lung disease that requires&#xD;
             oxygen therapy or is thought to require oxygen therapy within 1 year prior to step 1&#xD;
             registration&#xD;
&#xD;
          -  History of (non-infectious) pneumonitis that required steroids or current pneumonitis&#xD;
&#xD;
          -  Clinically apparent jaundice and/or known coagulation defects&#xD;
&#xD;
          -  Active or prior documented autoimmune or inflammatory disorders (including&#xD;
             inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with&#xD;
             the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome,&#xD;
             or Wegener syndrome [granulomatosis with polyangiitis], Graves' disease, rheumatoid&#xD;
             arthritis, hypophysitis, uveitis, etc.)&#xD;
&#xD;
               -  The following are exceptions to this criterion:&#xD;
&#xD;
                    -  Patients with vitiligo or alopecia;&#xD;
&#xD;
                    -  Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on&#xD;
                       hormone replacement;&#xD;
&#xD;
                    -  Any chronic skin condition that does not require systemic therapy;&#xD;
&#xD;
                    -  Patients without active disease in the last 5 years may be included but only&#xD;
                       after consultation with the medical oncology study chair;&#xD;
&#xD;
                    -  Patients with celiac disease controlled by diet alone&#xD;
&#xD;
          -  History of active primary immunodeficiency including, but not limited to acquired&#xD;
             immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and&#xD;
             Prevention (CDC) definition; Note: human immunodeficiency virus (HIV) testing is not&#xD;
             required for entry into this protocol; the need to exclude patients with AIDS from&#xD;
             this protocol is necessary because the treatment involved in this protocol may be&#xD;
             immunosuppressive; patients with known HIV, CD4 counts &gt;= 200/uL, and undetectable&#xD;
             viral loads who are stable on an antiretroviral regimen may be included&#xD;
&#xD;
          -  Current or prior use of immunosuppressive medication within 14 days before step 1&#xD;
             registration, with the exceptions of intranasal and inhaled corticosteroids or&#xD;
             systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of&#xD;
             prednisone, or an equivalent corticosteroid&#xD;
&#xD;
          -  Receipt of live attenuated vaccination within 30 days prior to step 1 registration&#xD;
&#xD;
          -  Medical or psychiatric illness which would compromise the patient's ability to&#xD;
             tolerate treatment or limit compliance with study requirements&#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 during treatment and&#xD;
             for 6 months after the last dose of cetuximab or MEDI14736 (durvalumab); this&#xD;
             exclusion is necessary because the treatment involved in this study may be&#xD;
             significantly teratogenic; women who are breastfeeding are also excluded&#xD;
&#xD;
          -  Prior allergic reaction or hypersensitivity to cetuximab or MEDI4736 (durvalumab) or&#xD;
             any of study drug excipients&#xD;
&#xD;
          -  History of allogenic organ transplantation&#xD;
&#xD;
          -  Uncontrolled hypertension&#xD;
&#xD;
          -  Uncontrolled cardiac arrhythmia&#xD;
&#xD;
          -  Uncontrolled serious chronic gastrointestinal condition associated with diarrhea&#xD;
&#xD;
          -  Active infection including tuberculosis (clinical evaluation that includes clinical&#xD;
             history, physical examination and radiographic findings, and tuberculosis [TB] testing&#xD;
             in line with local practice), hepatitis B (known positive hepatitis B virus [HBV]&#xD;
             surface antigen [HBsAg] result), hepatitis C; patients with a past or resolved HBV&#xD;
             infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence&#xD;
             of HBsAg) are eligible; patients positive for hepatitis C (hepatitis C virus [HCV])&#xD;
             antibody are eligible only if polymerase chain reaction is negative for HCV&#xD;
             ribonucleic acid (RNA)&#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>Loren K Mell</last_name>
    <role>Principal Investigator</role>
    <affiliation>NRG Oncology</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Alabama at Birmingham Cancer Center</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35233</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of South Alabama Mitchell Cancer Institute</name>
      <address>
        <city>Mobile</city>
        <state>Alabama</state>
        <zip>36688</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Banner MD Anderson Cancer Center</name>
      <address>
        <city>Gilbert</city>
        <state>Arizona</state>
        <zip>85234</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CTCA at Western Regional Medical Center</name>
      <address>
        <city>Goodyear</city>
        <state>Arizona</state>
        <zip>85338</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>University of Arizona Cancer Center-North Campus</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85719</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente-Deer Valley Medical Center</name>
      <address>
        <city>Antioch</city>
        <state>California</state>
        <zip>94531</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>Alta Bates Summit Medical Center-Herrick Campus</name>
      <address>
        <city>Berkeley</city>
        <state>California</state>
        <zip>94704</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>City of Hope Comprehensive Cancer Center</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente Dublin</name>
      <address>
        <city>Dublin</city>
        <state>California</state>
        <zip>94568</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente-Fremont</name>
      <address>
        <city>Fremont</city>
        <state>California</state>
        <zip>94538</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fresno Cancer Center</name>
      <address>
        <city>Fresno</city>
        <state>California</state>
        <zip>93720</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente-Fresno</name>
      <address>
        <city>Fresno</city>
        <state>California</state>
        <zip>93720</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>Cedars Sinai Medical Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90048</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente-Modesto</name>
      <address>
        <city>Modesto</city>
        <state>California</state>
        <zip>95356</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-Oakland</name>
      <address>
        <city>Oakland</city>
        <state>California</state>
        <zip>94611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stanford Cancer Institute Palo Alto</name>
      <address>
        <city>Palo Alto</city>
        <state>California</state>
        <zip>94304</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VA Palo Alto Health Care System</name>
      <address>
        <city>Palo Alto</city>
        <state>California</state>
        <zip>94304</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>Kaiser Permanente-Richmond</name>
      <address>
        <city>Richmond</city>
        <state>California</state>
        <zip>94801</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>Kaiser Permanente-Roseville</name>
      <address>
        <city>Roseville</city>
        <state>California</state>
        <zip>95661</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>Kaiser Permanente Downtown Commons</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95814</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>University of California Davis Comprehensive Cancer Center</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente-South Sacramento</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95823</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>Kaiser Permanente-San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94115</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>UCSF Medical Center-Mission Bay</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94158</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente-Santa Teresa-San Jose</name>
      <address>
        <city>San Jose</city>
        <state>California</state>
        <zip>95119</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente San Leandro</name>
      <address>
        <city>San Leandro</city>
        <state>California</state>
        <zip>94577</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser San Rafael-Gallinas</name>
      <address>
        <city>San Rafael</city>
        <state>California</state>
        <zip>94903</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente Medical Center - Santa Clara</name>
      <address>
        <city>Santa Clara</city>
        <state>California</state>
        <zip>95051</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente-Santa Rosa</name>
      <address>
        <city>Santa Rosa</city>
        <state>California</state>
        <zip>95403</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>City of Hope South Pasadena</name>
      <address>
        <city>South Pasadena</city>
        <state>California</state>
        <zip>91030</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>Kaiser Permanente-South San Francisco</name>
      <address>
        <city>South San Francisco</city>
        <state>California</state>
        <zip>94080</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente-Stockton</name>
      <address>
        <city>Stockton</city>
        <state>California</state>
        <zip>95210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Torrance Memorial Physician Network - Cancer Care</name>
      <address>
        <city>Torrance</city>
        <state>California</state>
        <zip>90505</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Torrance Memorial Medical Center</name>
      <address>
        <city>Torrance</city>
        <state>California</state>
        <zip>90509</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gene Upshaw Memorial Tahoe Forest Cancer Center</name>
      <address>
        <city>Truckee</city>
        <state>California</state>
        <zip>96161</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente Medical Center-Vacaville</name>
      <address>
        <city>Vacaville</city>
        <state>California</state>
        <zip>95688</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente-Vallejo</name>
      <address>
        <city>Vallejo</city>
        <state>California</state>
        <zip>94589</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente-Walnut Creek</name>
      <address>
        <city>Walnut Creek</city>
        <state>California</state>
        <zip>94596</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>Memorial Hospital North</name>
      <address>
        <city>Colorado Springs</city>
        <state>Colorado</state>
        <zip>80920</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Poudre Valley Hospital</name>
      <address>
        <city>Fort Collins</city>
        <state>Colorado</state>
        <zip>80524</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>Smilow Cancer Hospital-Hamden Care Center</name>
      <address>
        <city>Hamden</city>
        <state>Connecticut</state>
        <zip>06518</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yale University</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06520</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Smilow Cancer Hospital Care Center-Trumbull</name>
      <address>
        <city>Trumbull</city>
        <state>Connecticut</state>
        <zip>06611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Smilow Cancer Hospital Care Center - Waterford</name>
      <address>
        <city>Waterford</city>
        <state>Connecticut</state>
        <zip>06385</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beebe South Coastal Health Campus</name>
      <address>
        <city>Frankford</city>
        <state>Delaware</state>
        <zip>19945</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Helen F Graham Cancer Center</name>
      <address>
        <city>Newark</city>
        <state>Delaware</state>
        <zip>19713</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beebe Health Campus</name>
      <address>
        <city>Rehoboth Beach</city>
        <state>Delaware</state>
        <zip>19971</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UM Sylvester Comprehensive Cancer Center at Coral Gables</name>
      <address>
        <city>Coral Gables</city>
        <state>Florida</state>
        <zip>33146</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UM Sylvester Comprehensive Cancer Center at Deerfield Beach</name>
      <address>
        <city>Deerfield Beach</city>
        <state>Florida</state>
        <zip>33442</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baptist MD Anderson Cancer Center</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32207</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Miami Miller School of Medicine-Sylvester Cancer Center</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Moffitt Cancer Center</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Grady Health System</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory University Hospital Midtown</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30308</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory University Hospital/Winship Cancer Institute</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Augusta University Medical Center</name>
      <address>
        <city>Augusta</city>
        <state>Georgia</state>
        <zip>30912</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hawaii Cancer Care Inc - Waterfront Plaza</name>
      <address>
        <city>Honolulu</city>
        <state>Hawaii</state>
        <zip>96813</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-Caldwell</name>
      <address>
        <city>Caldwell</city>
        <state>Idaho</state>
        <zip>83605</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Alphonsus Cancer Care Center-Nampa</name>
      <address>
        <city>Nampa</city>
        <state>Idaho</state>
        <zip>83687</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwestern University</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</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>University of Illinois</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>Crossroads Cancer Center</name>
      <address>
        <city>Effingham</city>
        <state>Illinois</state>
        <zip>62401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Western Illinois Cancer Treatment Center</name>
      <address>
        <city>Galesburg</city>
        <state>Illinois</state>
        <zip>61401</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 North Hospital</name>
      <address>
        <city>Carmel</city>
        <state>Indiana</state>
        <zip>46032</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>Parkview Regional Medical Center</name>
      <address>
        <city>Fort Wayne</city>
        <state>Indiana</state>
        <zip>46845</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Indiana University/Melvin and Bren Simon Cancer Center</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sidney and Lois Eskenazi Hospital</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Community Cancer Center East</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46219</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Community Cancer Center South</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46227</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Community Cancer Center North</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46256</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mercy Cancer Center-West Lakes</name>
      <address>
        <city>Clive</city>
        <state>Iowa</state>
        <zip>50325</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Iowa Methodist Medical Center</name>
      <address>
        <city>Des Moines</city>
        <state>Iowa</state>
        <zip>50309</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mercy Medical Center - Des Moines</name>
      <address>
        <city>Des Moines</city>
        <state>Iowa</state>
        <zip>50314</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>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>Salina Regional Health Center</name>
      <address>
        <city>Salina</city>
        <state>Kansas</state>
        <zip>67401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kansas Hospital-Westwood Cancer Center</name>
      <address>
        <city>Westwood</city>
        <state>Kansas</state>
        <zip>66205</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>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>Norton Hospital Pavilion and Medical Campus</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The James Graham Brown Cancer Center at University of Louisville</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Norton Brownsboro Hospital and Medical Campus</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40241</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>East Jefferson General Hospital</name>
      <address>
        <city>Metairie</city>
        <state>Louisiana</state>
        <zip>70006</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Greater Baltimore Medical Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21204</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>Lahey Hospital and Medical Center</name>
      <address>
        <city>Burlington</city>
        <state>Massachusetts</state>
        <zip>01805</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Joseph Mercy Hospital</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Michigan Comprehensive Cancer Center</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>McLaren Cancer Institute-Bay City</name>
      <address>
        <city>Bay City</city>
        <state>Michigan</state>
        <zip>48706</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Joseph Mercy Brighton</name>
      <address>
        <city>Brighton</city>
        <state>Michigan</state>
        <zip>48114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Henry Ford Cancer Institute-Downriver</name>
      <address>
        <city>Brownstown</city>
        <state>Michigan</state>
        <zip>48183</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Joseph Mercy Canton</name>
      <address>
        <city>Canton</city>
        <state>Michigan</state>
        <zip>48188</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Joseph Mercy Chelsea</name>
      <address>
        <city>Chelsea</city>
        <state>Michigan</state>
        <zip>48118</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>McLaren Cancer Institute-Clarkston</name>
      <address>
        <city>Clarkston</city>
        <state>Michigan</state>
        <zip>48346</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Henry Ford Macomb Hospital-Clinton Township</name>
      <address>
        <city>Clinton Township</city>
        <state>Michigan</state>
        <zip>48038</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wayne State University/Karmanos Cancer Institute</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</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>Weisberg Cancer Treatment Center</name>
      <address>
        <city>Farmington Hills</city>
        <state>Michigan</state>
        <zip>48334</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>Singh and Arora Hematology Oncology PC</name>
      <address>
        <city>Flint</city>
        <state>Michigan</state>
        <zip>48532</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Allegiance Health</name>
      <address>
        <city>Jackson</city>
        <state>Michigan</state>
        <zip>49201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Karmanos Cancer Institute at McLaren Greater Lansing</name>
      <address>
        <city>Lansing</city>
        <state>Michigan</state>
        <zip>48910</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mid-Michigan Physicians-Lansing</name>
      <address>
        <city>Lansing</city>
        <state>Michigan</state>
        <zip>48912</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sparrow Hospital</name>
      <address>
        <city>Lansing</city>
        <state>Michigan</state>
        <zip>48912</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-Northern Michigan</name>
      <address>
        <city>Petoskey</city>
        <state>Michigan</state>
        <zip>49770</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>McLaren-Port Huron</name>
      <address>
        <city>Port Huron</city>
        <state>Michigan</state>
        <zip>48060</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ascension Saint Mary's Hospital</name>
      <address>
        <city>Saginaw</city>
        <state>Michigan</state>
        <zip>48601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Henry Ford West Bloomfield Hospital</name>
      <address>
        <city>West Bloomfield</city>
        <state>Michigan</state>
        <zip>48322</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>Fairview Ridges Hospital</name>
      <address>
        <city>Burnsville</city>
        <state>Minnesota</state>
        <zip>55337</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Miller-Dwan Hospital</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>Unity Hospital</name>
      <address>
        <city>Fridley</city>
        <state>Minnesota</state>
        <zip>55432</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>Mayo Clinic in Rochester</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Coborn Cancer Center at Saint Cloud Hospital</name>
      <address>
        <city>Saint Cloud</city>
        <state>Minnesota</state>
        <zip>56303</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>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>Siteman Cancer Center at West County Hospital</name>
      <address>
        <city>Creve Coeur</city>
        <state>Missouri</state>
        <zip>63141</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</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>Siteman Cancer Center at Saint Peters Hospital</name>
      <address>
        <city>Saint Peters</city>
        <state>Missouri</state>
        <zip>63376</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>Kalispell Regional Medical Center</name>
      <address>
        <city>Kalispell</city>
        <state>Montana</state>
        <zip>59901</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>Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center</name>
      <address>
        <city>Lebanon</city>
        <state>New Hampshire</state>
        <zip>03756</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Basking Ridge</name>
      <address>
        <city>Basking Ridge</city>
        <state>New Jersey</state>
        <zip>07920</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hackensack University Medical Center</name>
      <address>
        <city>Hackensack</city>
        <state>New Jersey</state>
        <zip>07601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Monmouth</name>
      <address>
        <city>Middletown</city>
        <state>New Jersey</state>
        <zip>07748</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Bergen</name>
      <address>
        <city>Montvale</city>
        <state>New Jersey</state>
        <zip>07645</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>Montefiore Medical Center - Moses Campus</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10467</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>James J Peters VA Medical Center</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10468</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Roswell Park Cancer Institute</name>
      <address>
        <city>Buffalo</city>
        <state>New York</state>
        <zip>14263</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Commack</name>
      <address>
        <city>Commack</city>
        <state>New York</state>
        <zip>11725</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Westchester</name>
      <address>
        <city>Harrison</city>
        <state>New York</state>
        <zip>10604</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Laura and Isaac Perlmutter Cancer Center at NYU Langone</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</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>Stony Brook University Medical Center</name>
      <address>
        <city>Stony Brook</city>
        <state>New York</state>
        <zip>11794</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>State University of New York Upstate Medical University</name>
      <address>
        <city>Syracuse</city>
        <state>New York</state>
        <zip>13210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Nassau</name>
      <address>
        <city>Uniondale</city>
        <state>New York</state>
        <zip>11553</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Atrium Health Stanly/LCI-Albemarle</name>
      <address>
        <city>Albemarle</city>
        <state>North Carolina</state>
        <zip>28002</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UNC Lineberger Comprehensive Cancer Center</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27599</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Carolinas Medical Center/Levine Cancer Institute</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Atrium Health Pineville/LCI-Pineville</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Atrium Health Cabarrus/LCI-Concord</name>
      <address>
        <city>Concord</city>
        <state>North Carolina</state>
        <zip>28025</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Margaret R Pardee Memorial Hospital</name>
      <address>
        <city>Hendersonville</city>
        <state>North Carolina</state>
        <zip>28791</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Atrium Health Union/LCI-Union</name>
      <address>
        <city>Monroe</city>
        <state>North Carolina</state>
        <zip>28112</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>Cleveland Clinic Mercy Hospital</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>University of Cincinnati Cancer Center-UC Medical 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>MetroHealth Medical Center</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44109</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>Cleveland Clinic Cancer Center Mansfield</name>
      <address>
        <city>Mansfield</city>
        <state>Ohio</state>
        <zip>44906</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>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>ProMedica Flower Hospital</name>
      <address>
        <city>Sylvania</city>
        <state>Ohio</state>
        <zip>43560</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Cincinnati Cancer Center-West Chester</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>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>Good Samaritan Hospital</name>
      <address>
        <city>Corvallis</city>
        <state>Oregon</state>
        <zip>97330</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Providence Portland Medical Center</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Providence Saint Vincent Medical Center</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97225</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente Northwest</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97227</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jefferson Abington Hospital</name>
      <address>
        <city>Abington</city>
        <state>Pennsylvania</state>
        <zip>19001</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Crozer-Keystone Regional Cancer Center at Broomall</name>
      <address>
        <city>Broomall</city>
        <state>Pennsylvania</state>
        <zip>19008</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Christiana Care Health System-Concord Health Center</name>
      <address>
        <city>Chadds Ford</city>
        <state>Pennsylvania</state>
        <zip>19317</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>Penn State Milton S Hershey Medical Center</name>
      <address>
        <city>Hershey</city>
        <state>Pennsylvania</state>
        <zip>17033-0850</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Geisinger Medical Oncology-Lewisburg</name>
      <address>
        <city>Lewisburg</city>
        <state>Pennsylvania</state>
        <zip>17837</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lewistown Hospital</name>
      <address>
        <city>Lewistown</city>
        <state>Pennsylvania</state>
        <zip>17044</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Forbes Hospital</name>
      <address>
        <city>Monroeville</city>
        <state>Pennsylvania</state>
        <zip>15146</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fox Chase Cancer Center</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Temple University Hospital</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19140</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Allegheny General Hospital</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15212</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>Guthrie Medical Group PC-Robert Packer Hospital</name>
      <address>
        <city>Sayre</city>
        <state>Pennsylvania</state>
        <zip>18840</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>Wexford Health and Wellness Pavilion</name>
      <address>
        <city>Wexford</city>
        <state>Pennsylvania</state>
        <zip>15090</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>Asplundh Cancer Pavilion</name>
      <address>
        <city>Willow Grove</city>
        <state>Pennsylvania</state>
        <zip>19090</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical University of South Carolina</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</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>Rock Hill Radiation Therapy Center</name>
      <address>
        <city>Rock Hill</city>
        <state>South Carolina</state>
        <zip>29730</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>Avera Cancer Institute</name>
      <address>
        <city>Sioux Falls</city>
        <state>South Dakota</state>
        <zip>57105</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>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>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>University of Virginia Cancer Center</name>
      <address>
        <city>Charlottesville</city>
        <state>Virginia</state>
        <zip>22908</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sentara Norfolk General Hospital</name>
      <address>
        <city>Norfolk</city>
        <state>Virginia</state>
        <zip>23507</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VCU Massey Cancer Center at Stony Point</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23235</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Virginia Commonwealth University/Massey Cancer Center</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23298</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Washington Medical Center - Montlake</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>West Virginia University Healthcare</name>
      <address>
        <city>Morgantown</city>
        <state>West Virginia</state>
        <zip>26506</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Langlade Hospital and Cancer Center</name>
      <address>
        <city>Antigo</city>
        <state>Wisconsin</state>
        <zip>54409</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Vincent Hospital Cancer Center Green Bay</name>
      <address>
        <city>Green Bay</city>
        <state>Wisconsin</state>
        <zip>54301</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Vincent Hospital Cancer Center at Saint Mary's</name>
      <address>
        <city>Green Bay</city>
        <state>Wisconsin</state>
        <zip>54303</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>UW Cancer Center Johnson Creek</name>
      <address>
        <city>Johnson Creek</city>
        <state>Wisconsin</state>
        <zip>53038</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>Gundersen Lutheran Medical Center</name>
      <address>
        <city>La Crosse</city>
        <state>Wisconsin</state>
        <zip>54601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Wisconsin Carbone Cancer Center</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53792</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aurora Bay Area Medical Group-Marinette</name>
      <address>
        <city>Marinette</city>
        <state>Wisconsin</state>
        <zip>54143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Froedtert Menomonee Falls Hospital</name>
      <address>
        <city>Menomonee Falls</city>
        <state>Wisconsin</state>
        <zip>53051</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>ProHealth D N Greenwald Center</name>
      <address>
        <city>Mukwonago</city>
        <state>Wisconsin</state>
        <zip>53149</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ProHealth Oconomowoc Memorial Hospital</name>
      <address>
        <city>Oconomowoc</city>
        <state>Wisconsin</state>
        <zip>53066</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vince Lombardi Cancer Clinic-Sheboygan</name>
      <address>
        <city>Sheboygan</city>
        <state>Wisconsin</state>
        <zip>53081</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>UW Cancer Center at ProHealth Care</name>
      <address>
        <city>Waukesha</city>
        <state>Wisconsin</state>
        <zip>53188</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aspirus Regional Cancer Center</name>
      <address>
        <city>Wausau</city>
        <state>Wisconsin</state>
        <zip>54401</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>Froedtert West Bend Hospital/Kraemer Cancer Center</name>
      <address>
        <city>West Bend</city>
        <state>Wisconsin</state>
        <zip>53095</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>London Regional Cancer Program</name>
      <address>
        <city>London</city>
        <state>Ontario</state>
        <zip>N6A 4L6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Health Network-Princess Margaret Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 2M9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Research Institute of the McGill University Health Centre (MUHC)</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H3H 2R9</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_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>August 22, 2017</study_first_submitted>
  <study_first_submitted_qc>August 22, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 23, 2017</study_first_posted>
  <last_update_submitted>June 30, 2023</last_update_submitted>
  <last_update_submitted_qc>June 30, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 3, 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>Carcinoma, Squamous Cell</mesh_term>
    <mesh_term>Head and Neck Neoplasms</mesh_term>
    <mesh_term>Squamous Cell Carcinoma of Head and Neck</mesh_term>
    <mesh_term>Laryngeal Neoplasms</mesh_term>
    <mesh_term>Mouth Neoplasms</mesh_term>
    <mesh_term>Oropharyngeal Neoplasms</mesh_term>
    <mesh_term>Lip Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Antineoplastic Agents, Immunological</mesh_term>
    <mesh_term>Cetuximab</mesh_term>
    <mesh_term>Durvalumab</mesh_term>
    <mesh_term>Antibodies</mesh_term>
    <mesh_term>Immunoglobulins</mesh_term>
    <mesh_term>Antibodies, Monoclonal</mesh_term>
    <mesh_term>Immunoglobulin G</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03258554
org study id: NCI-2017-01522
secondary id: NCI-2017-01522
secondary id: NRG-HN004
secondary id: NRG-HN004
secondary id: U10CA180868
nct id: NCT03258554
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This phase II/III trial studies how well radiation therapy works with durvalumab or cetuximab
      in treating patients with head and neck cancer that has spread to a local and/or regional
      area of the body who cannot take cisplatin. Radiation therapy uses high energy x-rays to kill
      tumor cells and shrink tumors. Immunotherapy with monoclonal antibodies, such as durvalumab,
      may help the body's immune system attack the cancer, and may interfere with the ability of
      tumor cells to grow and spread. Cetuximab is a monoclonal antibody that may interfere with
      the ability of tumor cells to grow and spread. It is not known if radiation therapy with
      durvalumab will work better than the usual therapy of radiation therapy with cetuximab in
      treating patients with head and neck cancer.
PRIMARY OBJECTIVES:

      I. To determine the safety of radiotherapy (RT) with concurrent and adjuvant anti-PD-L1
      therapy (MEDI4736 [durvalumab]) is safe in patients with locoregionally advanced head and
      neck cancer (HNC) who have a contraindication to cisplatin. (Lead-in) II. To test the
      hypothesis that concurrent RT and anti-PD-L1 therapy improves progression free survival (PFS)
      compared to standard therapy (RT with concurrent cetuximab) in patients with locoregionally
      advanced HNC who have a contraindication to cisplatin. (Phase II) III. To test the hypothesis
      that concurrent RT and anti-PD-L1 therapy improves overall survival compared to standard
      therapy (RT with concurrent cetuximab) in patients with locoregionally advanced HNC who have
      a contraindication to cisplatin. (Phase III)

      SECONDARY OBJECTIVES:

      I. To compare toxicity using Common Terminology Criteria for Adverse Events (CTCAE) and
      Patient Reported Outcomes (PRO)-CTCAE between patients treated with RT + anti-PD-L1 therapy
      versus RT/cetuximab.

      II. To test the effect of anti-PD-L1 therapy in the subpopulation of patients with tumors
      that overexpress PD-L1.

      III. To compare overall survival, response (at 4-month fludeoxyglucose F-18 [FDG]-positron
      emission tomography [PET]-computed tomography [CT]), locoregional failure, distant
      metastasis, and competing mortality in the two arms by known risk factors, including p16
      status and omega score.

      IV. To test the hypothesis that MEDI4736 (durvalumab) therapy arm will have less decline in
      the physical function domain of European Organization for Research and Treatment of Cancer
      Core Questionnaire (EORTC QLQ-C30 version 3.0) based on the change in score from baseline to
      12 months from end of RT, compared to the cetuximab-RT arm in patients with locoregionally
      advanced HNC who have a contraindication to cisplatin.

      V. To test the hypothesis that MEDI4736 (durvalumab) therapy arm at 1 year (from end of RT)
      will have less decline in swallowing related quality of life (QOL) using the M. D. Anderson
      Dysphagia Inventory (MDADI) total composite score, based on the change in score from baseline
      to 12 months from end of RT, compared to the cetuximab-RT arm in patients who are medically
      unfit for cisplatin.

      VI. To compare swallowing related performance and function short and long term using the
      Performance Status Scale for Head & Neck Cancer Patients (PSS-HN).

      VII. To evaluate gastrostomy tube retention rates between arms.

      EXPLORATORY OBJECTIVES:

      I. To test the hypothesis that radiation combined with MEDI4736 (durvalumab) enhances the
      adaptive immune response using three types of immunophenotyping compared to radiation
      combined with cetuximab.

      II. To compare overall QOL short term (end RT-8 months) and long term (12-24 months from end
      of RT) between arms using the EORTC QLQ-C30 version 3.0/HN35.

      III. To evaluate swallowing related QOL short term (end RT-8 months) and long term (12-24
      months from end of RT) using the EORTC Head and Neck (HN)35 swallowing domain and MDADI
      (subscales) between arms in patients with locoregionally advanced HNC who have a
      contraindication to cisplatin.

      IV. To evaluate patient reported fatigue using the fatigue items in the EORTC QLQ and
      PRO-CTCAE.

      V. To compare clinician and patient reported toxicity using CTCAE and PRO CTCAE.

      VI. To explore health utilities between cetuximab and MEDI4736 (durvalumab) RT using the
      European Quality of Life 5 Dimensional-5 Level (EQ5D-5L).

      OUTLINE: Patients are randomized to 1 of 2 arms.

      ARM I: Patients receive cetuximab intravenously (IV) weekly over 60-120 minutes. Treatment
      repeats every week for up to 8 cycles in the absence of disease progression or unacceptable
      toxicity. Beginning 5-7 days after first cetuximab dose, patients undergo intensity modulated
      radiation therapy (IMRT) 5 fractions per week for up to 7 weeks.

      ARM II: Patients receive durvalumab IV over 60 minutes every 4 weeks. Treatment repeats every
      4 weeks for up to 7 cycles in the absence of disease progression or unacceptable toxicity.
      Beginning week 2, patients undergo IMRT 5 fractions per week for up to 7 weeks.

      After completion of study treatment, patients are followed up at 1 month, every 4 months for
      1 year, every 6 months for 2 years, then annually thereafter.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Dose-limiting toxicity (DLT) defined as the occurrence of an adverse event (AE) during the specified observation window (Lead -in)
time frame: Up to 4 weeks after radiation therapy (RT)
description: AEs will be graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
measure: Progression-free survival (PFS) (Phase II)
time frame: From randomization until first evidence of local, regional, or distant disease progression or recurrence, or death from any cause, assessed up to 3 years
description: PFS will be estimated using the Kaplan-Meier method. The difference in PFS between the two arms will be tested using a log-rank test.
measure: Overall survival (OS) (Phase III)
time frame: From randomization until death from any cause, assessed up to 3 years
description: OS will be estimated using the Kaplan-Meier method. The difference in OS between the two arms will be tested using a log-rank test. Exploratory analysis adjusting for important factors such as age, site, Zubrod performance status, and clinical stages will be conducted using Cox models.
measure: Locoregional failure (LRF)
time frame: From randomization until first evidence of local, regional disease progression or recurrence, or death from study cancer or unknown causes, assessed up to 3 years
description: LRF will be estimated by cumulative incidence methods and compared using a cause-specific log-rank test. All failure times will be measured from the date of study randomization to the date of failure or last follow up.
measure: Distant metastasis (DM)
time frame: From randomization until first evidence of distant metastasis, assessed up to 3 years
description: DM will be estimated by cumulative incidence methods and compared using a cause-specific log-rank test. All failure times will be measured from the date of study randomization to the date of failure or last follow up.
measure: Competing mortality
time frame: Up to 3 years
description: Will be estimated by cumulative incidence methods and the effects of other covariates will be assessed using the Generalized Competing Event Model for Cancer Risk model.
measure: Response on 4-month fludeoxyglucose F-18 (FDG)-positron emission tomography (PET)/computed tomography (CT)
time frame: Up to 4 months
description: Will be measured by Response Evaluation Criteria in Solid Tumors (RECIST). Response rates between the two arms will be compared using Fisher's exact test.
measure: Acute toxicity
time frame: Up to 180 days after the end of radiation therapy
description: The rates of adverse events will be estimated using a binomial distribution along with their associated 95% confidence intervals and will be compared using Fisher's exact test.
measure: Late toxicity
time frame: Up to 3 years
description: Late toxicities > 180 days after the end of radiation therapy. The rates of adverse events will be estimated using a binomial distribution along with their associated 95% confidence intervals and will be compared using Fisher's exact test.
measure: Change in quality of life (QOL) analysis
time frame: Baseline up to 12 months
description: Assessed using European Organization for Research and Treatment of Cancer Core Questionnaire (EORTC QLQ)/Head-and-Neck module (H&N35), EuroQol- 5 Dimension (EQ5D), M. D. Anderson Dysphagia Inventory (MDADI), patient reported outcomes (PRO)-CTCAE, geriatric screening (G8). The mean summary score of the EORTC QLQ/H&N35, EQ5D, MDADI, PRO-CTCAE, G8, CCI, and the subscales will be determined. The mean change from baseline at each time point will be summarized using mean and standard deviations for each arm. Mean change from baseline will be compared between the arms using a two sample t test. If data normality assumptions are not met, the Wilcoxon rank sum test will be used to test the hypothesis. Mean change from baseline will be tested using an omnibus F test followed by individual comparisons of change scores at different time points within each treatment group. The same analysis will be conducted for between group comparisons at each time point.
measure: Change in swallowing QOL using total composite M. D. Anderson Dysphagia Inventory (MDADI) score
time frame: Baseline up to 1 year
description: The mean change from baseline at each time point will be summarized using mean and standard deviations for each arm. Mean change from baseline will be compared between the arms using a two sample t test. If data normality assumptions are not met, the Wilcoxon rank sum test will be used to test the hypothesis.
measure: Translational research, including PD-L1 and p16
time frame: Up to 3 years
description: Analyses of interaction between treatment arm and marker status will be done. Additionally toxicity for the two arms by marker status will be compared. Univariable and multivariable analysis will be performed using the Cox proportional hazards model for OS. Potential covariates evaluated for the multivariate models would be assigned treatment, age, Zubrod performance status, T-stage, N-stage, primary site, smoking history, other risk factors, as well as p16 and/PD-L1.
measure: Secondary biomarker analysis
time frame: Baseline up to 4 months after RT
description: Will perform multiparametric flow cytometry on peripheral mononuclear cells (PBMC) from patient-derived blood samples to quantify changes in immune cell frequency and activation status before, during and after radiation combined with cetuximab or radiation combined with durvalumab. To assess the statistical significance of pre- to post-treatment changes in levels of immunoglobulin (Ig)Gs as well as other markers, normalized signal intensities (log2) will be tested using a paired t test within an arm and two sample t test between the two arms. If the distribution assumption is violated for the t tests, nonparametric tests, such as the Wilcoxon signed-rank test will be considered. Lastly, the association between PFS and OS and post-treatment changes in frequency and activation state of T-cells, clonality and diversity of T cell receptor (TCR), and IgG levels will be evaluated using a two-sided Wald test at 0.05 level on the basis of Cox models.
measure: Patient Reported Outcomes-Common Terminology Criteria for Adverse Events (PRO-CTCAE)
time frame: Up to 3 years
description: PRO-CTCAE is not intended for expedited reporting, real time review or safety reporting. PRO-CTCAE data are exploratory and not currently intended for use in data safety monitoring or adverse event stopping rules.
measure: QOL endpoints using other items in EORTC QLQ/HN35, EQ5D and MDADI subscales
time frame: Up to 12-24 months from end of RT
description: The mean change from baseline at each time point will be summarized using mean and standard deviations for each arm. Mean change from baseline will be compared between the arms using a two sample t test. If data normality assumptions are not met, the Wilcoxon rank sum test will be used to test the hypothesis. Mean change from baseline will be tested using an omnibus F test followed by individual comparisons of change scores at different time points within each treatment group. The same analysis will be conducted for between group comparisons at each time point.
arm group label: Arm I (cetuximab, radiation therapy)
arm group type: Active Comparator
description: Patients receive cetuximab IV weekly over 60-120 minutes. Treatment repeats every week for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Beginning 5-7 days after first cetuximab dose, patients undergo IMRT 5 fractions per week for up to 7 weeks.
arm group label: Arm II (durvalumab, radiation therapy)
arm group type: Experimental
description: Patients receive durvalumab IV over 60 minutes every 4 weeks. Treatment repeats every 4 weeks for up to 7 cycles in the absence of disease progression or unacceptable toxicity. Beginning week 2, patients undergo IMRT 5 fractions per week for up to 7 weeks.
intervention type: Biological
intervention name: Cetuximab
description: Given IV
arm group label: Arm I (cetuximab, radiation therapy)
other name: Cetuximab Biosimilar CDP-1
other name: Cetuximab Biosimilar CMAB009
other name: Cetuximab Biosimilar KL 140
other name: Chimeric Anti-EGFR Monoclonal Antibody
other name: Chimeric MoAb C225
other name: Chimeric Monoclonal Antibody C225
other name: Erbitux
other name: IMC-C225
intervention type: Biological
intervention name: Durvalumab
description: Given IV
arm group label: Arm II (durvalumab, radiation therapy)
other name: Imfinzi
other name: Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer
other name: MEDI-4736
other name: MEDI4736
intervention type: Radiation
intervention name: Intensity-Modulated Radiation Therapy
description: Undergo IMRT
arm group label: Arm I (cetuximab, radiation therapy)
arm group label: Arm II (durvalumab, radiation therapy)
other name: IMRT
other name: Intensity modulated radiation therapy (procedure)
other name: Intensity Modulated RT
other name: Intensity-Modulated Radiotherapy
other name: Radiation, Intensity-Modulated Radiotherapy
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Arm I (cetuximab, radiation therapy)
arm group label: Arm II (durvalumab, radiation therapy)
intervention type: Other
intervention name: Quality-of-Life Assessment
description: Ancillary studies
arm group label: Arm I (cetuximab, radiation therapy)
arm group label: Arm II (durvalumab, radiation therapy)
other name: Quality of Life Assessment
intervention type: Other
intervention name: Questionnaire Administration
description: Ancillary studies
arm group label: Arm I (cetuximab, radiation therapy)
arm group label: Arm II (durvalumab, radiation therapy)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Loren K Mell
role: Principal Investigator
affiliation: NRG Oncology
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country: Canada
country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Squamous Cell
mesh term: Head and Neck Neoplasms
mesh term: Squamous Cell Carcinoma of Head and Neck
mesh term: Laryngeal Neoplasms
mesh term: Mouth Neoplasms
mesh term: Oropharyngeal Neoplasms
mesh term: Lip Neoplasms
mesh term: Antineoplastic Agents, Immunological
mesh term: Cetuximab
mesh term: Durvalumab
mesh term: Antibodies
mesh term: Immunoglobulins
mesh term: Antibodies, Monoclonal
mesh term: Immunoglobulin G