<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/NCT03007407</url>
  </required_header>
  <id_info>
    <org_study_id>NSABP FC-9</org_study_id>
    <secondary_id>ESR-15-11514</secondary_id>
    <nct_id>NCT03007407</nct_id>
  </id_info>
  <brief_title>Study of Durvalumab and Tremelimumab After Radiation for Microsatellite Stable Metastatic Colorectal Cancer Progressing on Chemotherapy</brief_title>
  <official_title>A Phase II Study of the Dual Immune Checkpoint Blockade With Durvalumab (MEDI4736) Plus Tremelimumab Following Palliative Hypofractionated Radiation in Patients With Microsatellite Stable (MSS) Metastatic Colorectal Cancer Progressing on Chemotherapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>NSABP Foundation Inc</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>NSABP Foundation Inc</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 study is being done to look at the safety and response to the combination of two&#xD;
      investigational drugs, tremelimumab and durvalumab, when given after radiation therapy for&#xD;
      patients with microsatellite stable (MSS) metastatic colorectal cancer. Tremelimumab and&#xD;
      durvalumab recognize specific proteins on the surface of cancer cells and trigger the immune&#xD;
      system to destroy the cancer cells.&#xD;
&#xD;
      In order to learn more about certain characteristics of colorectal cancer tumors, this study&#xD;
      includes special research tests using samples from diagnostic tumors, fresh tumor samples&#xD;
      from an area where the cancer has spread, and blood samples.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The FC-9 study is designed as a phase II, open label, single arm study of the dual immune&#xD;
      checkpoint blockade with the combination of durvalumab and tremelimumab following&#xD;
      hypofractionated palliative radiation in patients with microsatellite stable (MSS) metastatic&#xD;
      colorectal cancer (mCRC) who have progressed on chemotherapy. The primary aim is to determine&#xD;
      the anti-tumor efficacy of the dual immune checkpoint blockade with durvalumab plus&#xD;
      tremelimumab. The secondary aims are to determine the clinical benefit rate, duration of&#xD;
      response, tolerability and correlates of response. Tumor response at unirradiated target&#xD;
      lesions will be measured at baseline and every 2 cycles using RECIST 1.1.&#xD;
&#xD;
      Following three doses of hypofractionated palliative radiation (Days -2, -1, and Day 0 prior&#xD;
      to Cycle 1), patients will receive the combination of tremelimumab (75 mg IV infusion) and&#xD;
      durvalumab (1500 mg IV infusion) on Day 1 for 4 cycles. Beginning with Cycle 5 through Cycle&#xD;
      24, patients will receive durvalumab alone (1500 mg/IV infusion) on Day 1 of each 28 day&#xD;
      cycle.&#xD;
&#xD;
      The sample size will be between 12 and 21 evaluable patients. Twelve evaluable patients will&#xD;
      be treated in the first stage of the study. If there are no responses among the 12 evaluable&#xD;
      patients, the study will be terminated. If the study goes on to the second stage, a total of&#xD;
      21 evaluable patients will be studied.&#xD;
&#xD;
      Submission of tumor tissue and blood samples for FC-9 correlative science studies will be a&#xD;
      study requirement for all patients. Requirements will include archived tumor samples from the&#xD;
      diagnostic biopsy; additional biopsies of fresh tissue from an accessible lesion prior to&#xD;
      radiation therapy and after 2 cycles of study therapy; and blood sample collections.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 31, 2017</start_date>
  <completion_date type="Actual">August 9, 2019</completion_date>
  <primary_completion_date type="Actual">April 18, 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall Objective Response Rate (ORR) of Dual Immune Checkpoint Blockade by RECIST 1.1</measure>
    <time_frame>Through treatment, up to 1.3 years</time_frame>
    <description>Complete Response (CR): Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be &lt;10mm on the short axis.&#xD;
Partial Response (PR): 30% or more decrease in the sum of diameters of target lesions. The reference the baseline sums of diameters. Progressive Disease (PD): 20% or more increase in the sum of diameters of target lesions. The reference is the smallest sum while on study (including the baseline sum if that is the smallest on study). In addition to the relative 20% increase, the sum must also demonstrate an absolute increase 5mm or more. (Note: any appearance of one or more new lesions is also considered progression).Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. The reference is the smallest sum of diameters while on study.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Patients Who Have Achieved Clinical Benefit</measure>
    <time_frame>At 16 weeks</time_frame>
    <description>Percentage of patients who have achieved clinical benefit defined as CR (complete response) and PR (partial response) and stable disease that lasts at least 4 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median Duration of Response to mCRC (Metastic Colorectal Cancer) Responds to Study Therapy</measure>
    <time_frame>Through study completetion (1.3 years)</time_frame>
    <description>Median time from study entry until documentation of progression (years) in half of the patients as determined by RECIST 1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of Adverse Events Assessed by CTCAE 4.0, From Beginning of Treatment to 90 Days After Last Dose</measure>
    <time_frame>During treatment (max of 12 cycles; each cycle 28 days) to 90 days after last dose of study therapy</time_frame>
    <description>Frequency of adverse events categorized using the NCI Common Terminology Criteria for Adverse Events version 4.0</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">33</enrollment>
  <condition>Colorectal Cancer Metastatic</condition>
  <arm_group>
    <arm_group_label>durvalumab and tremelimumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>durvalumab</intervention_name>
    <description>Following three doses of hypofractionated palliative radiation (Days -2, -1, and Day 0 prior to Cycle 1), patients will receive durvalumab (1500 mg IV infusion) on Day 1 for 4 cycles (in combination with tremelimumab). Beginning with Cycle 5 through Cycle 12, patients will receive durvalumab alone (1500 mg/IV infusion) on Day 1 of each 28 day cycle.</description>
    <arm_group_label>durvalumab and tremelimumab</arm_group_label>
    <other_name>MEDI4736</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tremelimumab</intervention_name>
    <description>Following three doses of hypofractionated palliative radiation (Days -2, -1, and Day 0 prior to Cycle 1), patients will receive tremelimumab (75 mg IV infusion) on Day 1 for 4 cycles (in combination with durvalumab).</description>
    <arm_group_label>durvalumab and tremelimumab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  The ECOG performance status must be 0 or 1.&#xD;
&#xD;
          -  There must be histologic confirmation of a diagnosis of colorectal adenocarcinoma.&#xD;
&#xD;
          -  The tumor must have been determined to be microsatellite stable (MSS).&#xD;
&#xD;
          -  There must be documentation by positron emission tomography (PET)/computed tomography&#xD;
             (CT) scan, CT scan, or magnetic resonance imaging (MRI), that the patient has evidence&#xD;
             of measurable metastatic disease per RECIST 1.1.&#xD;
&#xD;
          -  Patients must have an accessible metastatic lesion for pretreatment core biopsy.&#xD;
&#xD;
          -  Unless either drug is medically contraindicated, patients must have received&#xD;
             oxaliplatin and irinotecan as part of standard metastatic chemotherapy regimens.&#xD;
&#xD;
          -  The patient must have multiple sites of metastatic disease with at least one lesion&#xD;
             amenable to treatment with stereotactic radiation therapy (SBRT) in the lung or liver&#xD;
             and at least one lesion not being irradiated and meeting RECIST 1.1.&#xD;
&#xD;
          -  At the time of study entry, blood counts performed within 2 weeks prior to study entry&#xD;
             must meet the following criteria:&#xD;
&#xD;
               -  ANC (absolute neutrophil count) must be greater than or equal to 1500/mm3,&#xD;
&#xD;
               -  Platelet count must be greater than or equal to 100,000/mm3; and&#xD;
&#xD;
               -  Hemoglobin must be greater than or equal to 9 g/dL.&#xD;
&#xD;
          -  The following criteria for evidence of adequate hepatic function performed within 2&#xD;
             weeks prior to study entry must be met:&#xD;
&#xD;
               -  Total bilirubin must be less than or equal to 1.5 x ULN (upper limit of normal)&#xD;
                  for the lab unless the patient has a bilirubin elevation greater than 1.5 x ULN&#xD;
                  to 3 x ULN due to Gilbert's disease or similar syndrome involving slow&#xD;
                  conjugation of bilirubin; and&#xD;
&#xD;
               -  AST (aspartate aminotransferase)and ALT (alanine transaminase) must be less than&#xD;
                  or equal to 2.5 x ULN for the lab with the following exception: for patients with&#xD;
                  documented liver metastases, AST and ALT must be less than or equal to 5 x ULN.&#xD;
&#xD;
          -  Adequate renal function within 4 weeks prior to study entry, defined as serum&#xD;
             creatinine less than or equal to 1.5 x ULN for the lab or measured or calculated&#xD;
             creatinine clearance greater than 40 mL/min by Cockcroft-Gault formula.&#xD;
&#xD;
          -  All hematologic, gastrointestinal, and genitourinary chemotherapy toxicities must be&#xD;
             less than Grade 2 at the time study therapy is to begin. (Note: Transfusions may be&#xD;
             used to correct hemoglobin for patients experiencing anemia from therapy who otherwise&#xD;
             would be eligible for the study.&#xD;
&#xD;
          -  Patients with reproductive potential (male/female) must agree to use accepted and&#xD;
             highly effective methods of contraception while receiving study therapy and for at&#xD;
             least 6 months after the completion of study therapy. The definition of effective&#xD;
             method of contraception will be based on the investigator's discretion.&#xD;
&#xD;
          -  Female patients must either be of non-reproductive potential (i.e., post-menopausal by&#xD;
             history: greater than or equal to 60 years old and no menses for greater than or equal&#xD;
             to 1 year without an alternative medical cause; OR history of hysterectomy, OR history&#xD;
             of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a&#xD;
             negative serum pregnancy test upon study entry.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of anal or small bowel carcinoma.&#xD;
&#xD;
          -  Colorectal cancer other than adenocarcinoma, e.g., sarcoma, lymphoma, carcinoid.&#xD;
&#xD;
          -  Previous therapy with any PD-1 or PD-L1 (programmed cell death-1 (PD-1) protein,&#xD;
             programmed death ligand-1 (PDL-1) protein inhibitor including durvalumab or anti-CTLA4&#xD;
             (including tremelimumab) for any malignancy.&#xD;
&#xD;
          -  Receipt of live attenuated vaccination within 30 days prior to study entry or within&#xD;
             30 days of receiving study therapy.&#xD;
&#xD;
          -  Active or chronic hepatitis B or hepatitis C.&#xD;
&#xD;
          -  Symptomatic or uncontrolled brain metastases requiring concurrent treatments,&#xD;
             uncontrolled spinal cord compression, carcinomatous meningitis, or new evidence of&#xD;
             brain or leptomeningeal disease; uncontrolled seizures.&#xD;
&#xD;
          -  Active infection or chronic infection requiring chronic suppressive antibiotics.&#xD;
&#xD;
          -  Active or documented inflammatory disease.&#xD;
&#xD;
          -  Known history of human immunodeficiency virus (HIV) or acquired&#xD;
             immunodeficiency-related (AIDS) illnesses.&#xD;
&#xD;
          -  Current or prior use of immunosuppressive medication within 28 days before the first&#xD;
             dose of study therapy with the exceptions of intranasal corticosteroids or systemic&#xD;
             corticosteroids at physiological doses that do not exceed 10mg/day of prednisone or an&#xD;
             equivalent corticosteroid.&#xD;
&#xD;
          -  History of allogeneic organ transplantation.&#xD;
&#xD;
          -  Any of the following cardiac conditions:&#xD;
&#xD;
               -  Documented NYHA (New York Heart Association) Class III or IV congestive heart&#xD;
                  failure,&#xD;
&#xD;
               -  Myocardial infarction within 6 months prior to study entry,&#xD;
&#xD;
               -  Unstable angina within 6 months prior to study entry,&#xD;
&#xD;
               -  Symptomatic arrhythmia. If QTc (corrected QT interval) greater than or equal to&#xD;
                  470ms, confirmation of eligible QTc requires mean calculation from 2 additional&#xD;
                  electrocardiograms (ECGs) 2-5 minutes apart using Fridericia's Correction Formula&#xD;
                  (mean less than 470 ms).&#xD;
&#xD;
          -  Uncontrolled high blood pressure defined as systolic blood pressure (BP) greater than&#xD;
             or equal to 150 mmHg or diastolic BP greater than or equal to 100 mmHg with or without&#xD;
             anti-hypertensive medication. Patients with initial BP elevations are eligible if&#xD;
             initiation or adjustment of BP medication lowers pressure to meet entry criteria.&#xD;
&#xD;
          -  Active or prior documented inflammatory bowel disease (e.g., Crohn's disease,&#xD;
             ulcerative colitis).&#xD;
&#xD;
          -  Ongoing or active gastritis or peptic ulcer disease.&#xD;
&#xD;
          -  Active bleeding diatheses.&#xD;
&#xD;
          -  Known history of previous diagnosis of tuberculosis.&#xD;
&#xD;
          -  History of hypersensitivity to durvalumab or tremelimumab or any excipients of these&#xD;
             drugs.&#xD;
&#xD;
          -  Known history or confirmation of active pneumonia, pneumonitis, symptomatic&#xD;
             interstitial lung disease, or definitive evidence of interstitial lung disease&#xD;
             described on CT scan, MRI, or chest x-ray in asymptomatic patients; dyspnea at rest&#xD;
             requiring current continuous oxygen therapy.&#xD;
&#xD;
          -  Active or prior documented autoimmune disease within the past 2 years. (Note: Patients&#xD;
             with vitiligo, Grave disease, or psoriasis not requiring systemic treatment within the&#xD;
             past 2 years are eligible.)&#xD;
&#xD;
          -  Other malignancies unless the patient is considered to be disease-free and has&#xD;
             completed therapy for the malignancy greater than or equal to 12 months prior to study&#xD;
             entry. Patients with the following cancers are eligible if diagnosed and treated&#xD;
             within the past 12 months: carcinoma in situ of the cervix, and basal cell and&#xD;
             squamous cell carcinoma of the skin.&#xD;
&#xD;
          -  Psychiatric or addictive disorders or other conditions that, in the opinion of the&#xD;
             investigator, would preclude the patient from meeting the study requirements or&#xD;
             interfere with interpretation of study results.&#xD;
&#xD;
          -  Pregnancy or lactation at the time of study entry. (Note: Pregnancy testing should be&#xD;
             performed within 14 days prior to study entry according to institutional standards for&#xD;
             women of childbearing potential.)&#xD;
&#xD;
          -  Use of any investigational agent. Use and/or receipt of the last dose of anti-cancer&#xD;
             therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic&#xD;
             therapy, tumor embolization, monoclonal anti-bodies) within 14 days prior to the first&#xD;
             dose of study therapy.&#xD;
&#xD;
          -  Use of any investigational agent within 4 weeks of starting study therapy.&#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>Norman Wolmark, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>NSABP Foundation Inc</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>City of Hope</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Smilow Cancer Hospital at Yale-New Haven</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06510</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Smilow Cancer Hospital Care Center at North Haven</name>
      <address>
        <city>North Haven</city>
        <state>Connecticut</state>
        <zip>06473</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UF Health Davis Cancer Pavilion and Shands Med Plaza</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32608</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UF Health Shands Cancer Hospital</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32608</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UF Health Shands Hospital</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32610</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Florida</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32610</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Florida Health Cancer Center at Orlando Health</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centralia Oncology Clinic</name>
      <address>
        <city>Centralia</city>
        <state>Illinois</state>
        <zip>62801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Care Specialists of Central Illinois</name>
      <address>
        <city>Decatur</city>
        <state>Illinois</state>
        <zip>62526</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Care Specialists of Central Illinois/Crossroads Cancer Center</name>
      <address>
        <city>Effingham</city>
        <state>Illinois</state>
        <zip>62401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Care Specialists of Central Illinois-Swansea</name>
      <address>
        <city>Swansea</city>
        <state>Illinois</state>
        <zip>62226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Trinity Health Michigan</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</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Joseph Mercy-Brighton</name>
      <address>
        <city>Brighton</city>
        <state>Michigan</state>
        <zip>48114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Joseph Mercy-Canton</name>
      <address>
        <city>Canton</city>
        <state>Michigan</state>
        <zip>48188</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St Joseph Mercy-Chelsea</name>
      <address>
        <city>Chelsea</city>
        <state>Michigan</state>
        <zip>48118</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Thomas Jefferson University</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.</citation>
    <PMID>19097774</PMID>
  </reference>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>December 7, 2016</study_first_submitted>
  <study_first_submitted_qc>December 29, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 2, 2017</study_first_posted>
  <results_first_submitted>June 10, 2022</results_first_submitted>
  <results_first_submitted_qc>November 8, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">December 5, 2022</results_first_posted>
  <last_update_submitted>November 8, 2022</last_update_submitted>
  <last_update_submitted_qc>November 8, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 5, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>microsatellite stable</keyword>
  <keyword>MSS</keyword>
  <keyword>durvalumab</keyword>
  <keyword>tremelimumab</keyword>
  <keyword>mCRC</keyword>
  <keyword>NSABP</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colorectal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Durvalumab</mesh_term>
    <mesh_term>Tremelimumab</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>April 17, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/07/NCT03007407/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Durvalumab and Tremelimumab</title>
          <description>durvalumab: Following three doses of hypofractionated palliative radiation (Days -2, -1, and Day 0 prior to Cycle 1), patients will receive durvalumab (1500 mg IV infusion) on Day 1 for 4 cycles (in combination with tremelimumab). Beginning with Cycle 5 through Cycle 12, patients will receive durvalumab alone (1500 mg/IV infusion) on Day 1 of each 28 day cycle.&#xD;
Tremelimumab: Following three doses of hypofractionated palliative radiation (Days -2, -1, and Day 0 prior to Cycle 1), patients will receive tremelimumab (75 mg IV infusion) on Day 1 for 4 cycles (in combination with durvalumab).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="33"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Participant could identify as more than one race/ethnicity and may be counted in more than one race/ethnicity category.</population>
      <group_list>
        <group group_id="B1">
          <title>Durvalumab and Tremelimumab</title>
          <description>durvalumab: Following three doses of hypofractionated palliative radiation (Days -2, -1, and Day 0 prior to Cycle 1), patients will receive durvalumab (1500 mg IV infusion) on Day 1 for 4 cycles (in combination with tremelimumab). Beginning with Cycle 5 through Cycle 12, patients will receive durvalumab alone (1500 mg/IV infusion) on Day 1 of each 28 day cycle.&#xD;
Tremelimumab: Following three doses of hypofractionated palliative radiation (Days -2, -1, and Day 0 prior to Cycle 1), patients will receive tremelimumab (75 mg IV infusion) on Day 1 for 4 cycles (in combination with durvalumab).</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="21"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="58" lower_limit="37" upper_limit="71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Black</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Non Hispanic</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Overall Objective Response Rate (ORR) of Dual Immune Checkpoint Blockade by RECIST 1.1</title>
        <description>Complete Response (CR): Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be &lt;10mm on the short axis.&#xD;
Partial Response (PR): 30% or more decrease in the sum of diameters of target lesions. The reference the baseline sums of diameters. Progressive Disease (PD): 20% or more increase in the sum of diameters of target lesions. The reference is the smallest sum while on study (including the baseline sum if that is the smallest on study). In addition to the relative 20% increase, the sum must also demonstrate an absolute increase 5mm or more. (Note: any appearance of one or more new lesions is also considered progression).Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. The reference is the smallest sum of diameters while on study.</description>
        <time_frame>Through treatment, up to 1.3 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Durvalumab and Tremelimumab</title>
            <description>durvalumab: Following three doses of hypofractionated palliative radiation (Days -2, -1, and Day 0 prior to Cycle 1), patients will receive durvalumab (1500 mg IV infusion) on Day 1 for 4 cycles (in combination with tremelimumab). Beginning with Cycle 5 through Cycle 12, patients will receive durvalumab alone (1500 mg/IV infusion) on Day 1 of each 28 day cycle.&#xD;
Tremelimumab: Following three doses of hypofractionated palliative radiation (Days -2, -1, and Day 0 prior to Cycle 1), patients will receive tremelimumab (75 mg IV infusion) on Day 1 for 4 cycles (in combination with durvalumab).</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Objective Response Rate (ORR) of Dual Immune Checkpoint Blockade by RECIST 1.1</title>
          <description>Complete Response (CR): Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be &lt;10mm on the short axis.&#xD;
Partial Response (PR): 30% or more decrease in the sum of diameters of target lesions. The reference the baseline sums of diameters. Progressive Disease (PD): 20% or more increase in the sum of diameters of target lesions. The reference is the smallest sum while on study (including the baseline sum if that is the smallest on study). In addition to the relative 20% increase, the sum must also demonstrate an absolute increase 5mm or more. (Note: any appearance of one or more new lesions is also considered progression).Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. The reference is the smallest sum of diameters while on study.</description>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.52" lower_limit="1.17" upper_limit="30.38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Patients Who Have Achieved Clinical Benefit</title>
        <description>Percentage of patients who have achieved clinical benefit defined as CR (complete response) and PR (partial response) and stable disease that lasts at least 4 months</description>
        <time_frame>At 16 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Durvalumab and Tremelimumab</title>
            <description>durvalumab: Following three doses of hypofractionated palliative radiation (Days -2, -1, and Day 0 prior to Cycle 1), patients will receive durvalumab (1500 mg IV infusion) on Day 1 for 4 cycles (in combination with tremelimumab). Beginning with Cycle 5 through Cycle 12, patients will receive durvalumab alone (1500 mg/IV infusion) on Day 1 of each 28 day cycle.&#xD;
Tremelimumab: Following three doses of hypofractionated palliative radiation (Days -2, -1, and Day 0 prior to Cycle 1), patients will receive tremelimumab (75 mg IV infusion) on Day 1 for 4 cycles (in combination with durvalumab).</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Patients Who Have Achieved Clinical Benefit</title>
          <description>Percentage of patients who have achieved clinical benefit defined as CR (complete response) and PR (partial response) and stable disease that lasts at least 4 months</description>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.29" lower_limit="3.05" upper_limit="36.34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Median Duration of Response to mCRC (Metastic Colorectal Cancer) Responds to Study Therapy</title>
        <description>Median time from study entry until documentation of progression (years) in half of the patients as determined by RECIST 1.1.</description>
        <time_frame>Through study completetion (1.3 years)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Durvalumab and Tremelimumab</title>
            <description>durvalumab: Following three doses of hypofractionated palliative radiation (Days -2, -1, and Day 0 prior to Cycle 1), patients will receive durvalumab (1500 mg IV infusion) on Day 1 for 4 cycles (in combination with tremelimumab). Beginning with Cycle 5 through Cycle 12, patients will receive durvalumab alone (1500 mg/IV infusion) on Day 1 of each 28 day cycle.&#xD;
Tremelimumab: Following three doses of hypofractionated palliative radiation (Days -2, -1, and Day 0 prior to Cycle 1), patients will receive tremelimumab (75 mg IV infusion) on Day 1 for 4 cycles (in combination with durvalumab).</description>
          </group>
        </group_list>
        <measure>
          <title>Median Duration of Response to mCRC (Metastic Colorectal Cancer) Responds to Study Therapy</title>
          <description>Median time from study entry until documentation of progression (years) in half of the patients as determined by RECIST 1.1.</description>
          <units>years</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.85" lower_limit="0" upper_limit="NA">The upper limit of the 95% CI is infinite.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Frequency of Adverse Events Assessed by CTCAE 4.0, From Beginning of Treatment to 90 Days After Last Dose</title>
        <description>Frequency of adverse events categorized using the NCI Common Terminology Criteria for Adverse Events version 4.0</description>
        <time_frame>During treatment (max of 12 cycles; each cycle 28 days) to 90 days after last dose of study therapy</time_frame>
        <population>Number of participants analyzed represents the number of patients with toxicity information (29).</population>
        <group_list>
          <group group_id="O1">
            <title>Durvalumab and Tremelimumab</title>
            <description>durvalumab: Following three doses of hypofractionated palliative radiation (Days -2, -1, and Day 0 prior to Cycle 1), patients will receive durvalumab (1500 mg IV infusion) on Day 1 for 4 cycles (in combination with tremelimumab). Beginning with Cycle 5 through Cycle 12, patients will receive durvalumab alone (1500 mg/IV infusion) on Day 1 of each 28 day cycle.&#xD;
Tremelimumab: Following three doses of hypofractionated palliative radiation (Days -2, -1, and Day 0 prior to Cycle 1), patients will receive tremelimumab (75 mg IV infusion) on Day 1 for 4 cycles (in combination with durvalumab).</description>
          </group>
        </group_list>
        <measure>
          <title>Frequency of Adverse Events Assessed by CTCAE 4.0, From Beginning of Treatment to 90 Days After Last Dose</title>
          <description>Frequency of adverse events categorized using the NCI Common Terminology Criteria for Adverse Events version 4.0</description>
          <population>Number of participants analyzed represents the number of patients with toxicity information (29).</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Total</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From the first dose of study therapy until 90 days after the last dose of study therapy.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Durvalumab and Tremelimumab</title>
          <description>durvalumab: Following three doses of hypofractionated palliative radiation (Days -2, -1, and Day 0 prior to Cycle 1), patients will receive durvalumab (1500 mg IV infusion) on Day 1 for 4 cycles (in combination with tremelimumab). Beginning with Cycle 5 through Cycle 12, patients will receive durvalumab alone (1500 mg/IV infusion) on Day 1 of each 28 day cycle.&#xD;
Tremelimumab: Following three doses of hypofractionated palliative radiation (Days -2, -1, and Day 0 prior to Cycle 1), patients will receive tremelimumab (75 mg IV infusion) on Day 1 for 4 cycles (in combination with durvalumab).</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="29" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hypothyroidism</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dry Skin</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Itching</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Maculopapular rash</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Director, Department of Site and Study Management</name_or_title>
      <organization>NSABP Foundation</organization>
      <phone>1-800-270-3165</phone>
      <email>industrytrials@nsabp.org</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03007407
org study id: NSABP FC-9
secondary id: ESR-15-11514
nct id: NCT03007407
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This study is being done to look at the safety and response to the combination of two
      investigational drugs, tremelimumab and durvalumab, when given after radiation therapy for
      patients with microsatellite stable (MSS) metastatic colorectal cancer. Tremelimumab and
      durvalumab recognize specific proteins on the surface of cancer cells and trigger the immune
      system to destroy the cancer cells.

      In order to learn more about certain characteristics of colorectal cancer tumors, this study
      includes special research tests using samples from diagnostic tumors, fresh tumor samples
      from an area where the cancer has spread, and blood samples.
The FC-9 study is designed as a phase II, open label, single arm study of the dual immune
      checkpoint blockade with the combination of durvalumab and tremelimumab following
      hypofractionated palliative radiation in patients with microsatellite stable (MSS) metastatic
      colorectal cancer (mCRC) who have progressed on chemotherapy. The primary aim is to determine
      the anti-tumor efficacy of the dual immune checkpoint blockade with durvalumab plus
      tremelimumab. The secondary aims are to determine the clinical benefit rate, duration of
      response, tolerability and correlates of response. Tumor response at unirradiated target
      lesions will be measured at baseline and every 2 cycles using RECIST 1.1.

      Following three doses of hypofractionated palliative radiation (Days -2, -1, and Day 0 prior
      to Cycle 1), patients will receive the combination of tremelimumab (75 mg IV infusion) and
      durvalumab (1500 mg IV infusion) on Day 1 for 4 cycles. Beginning with Cycle 5 through Cycle
      24, patients will receive durvalumab alone (1500 mg/IV infusion) on Day 1 of each 28 day
      cycle.

      The sample size will be between 12 and 21 evaluable patients. Twelve evaluable patients will
      be treated in the first stage of the study. If there are no responses among the 12 evaluable
      patients, the study will be terminated. If the study goes on to the second stage, a total of
      21 evaluable patients will be studied.

      Submission of tumor tissue and blood samples for FC-9 correlative science studies will be a
      study requirement for all patients. Requirements will include archived tumor samples from the
      diagnostic biopsy; additional biopsies of fresh tissue from an accessible lesion prior to
      radiation therapy and after 2 cycles of study therapy; and blood sample collections.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall Objective Response Rate (ORR) of Dual Immune Checkpoint Blockade by RECIST 1.1
time frame: Through treatment, up to 1.3 years
description: Complete Response (CR): Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be <10mm on the short axis.
Partial Response (PR): 30% or more decrease in the sum of diameters of target lesions. The reference the baseline sums of diameters. Progressive Disease (PD): 20% or more increase in the sum of diameters of target lesions. The reference is the smallest sum while on study (including the baseline sum if that is the smallest on study). In addition to the relative 20% increase, the sum must also demonstrate an absolute increase 5mm or more. (Note: any appearance of one or more new lesions is also considered progression).Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. The reference is the smallest sum of diameters while on study.
measure: Percentage of Patients Who Have Achieved Clinical Benefit
time frame: At 16 weeks
description: Percentage of patients who have achieved clinical benefit defined as CR (complete response) and PR (partial response) and stable disease that lasts at least 4 months
measure: Median Duration of Response to mCRC (Metastic Colorectal Cancer) Responds to Study Therapy
time frame: Through study completetion (1.3 years)
description: Median time from study entry until documentation of progression (years) in half of the patients as determined by RECIST 1.1.
measure: Frequency of Adverse Events Assessed by CTCAE 4.0, From Beginning of Treatment to 90 Days After Last Dose
time frame: During treatment (max of 12 cycles; each cycle 28 days) to 90 days after last dose of study therapy
description: Frequency of adverse events categorized using the NCI Common Terminology Criteria for Adverse Events version 4.0
arm group label: durvalumab and tremelimumab
arm group type: Experimental
intervention type: Drug
intervention name: durvalumab
description: Following three doses of hypofractionated palliative radiation (Days -2, -1, and Day 0 prior to Cycle 1), patients will receive durvalumab (1500 mg IV infusion) on Day 1 for 4 cycles (in combination with tremelimumab). Beginning with Cycle 5 through Cycle 12, patients will receive durvalumab alone (1500 mg/IV infusion) on Day 1 of each 28 day cycle.
arm group label: durvalumab and tremelimumab
other name: MEDI4736
intervention type: Drug
intervention name: Tremelimumab
description: Following three doses of hypofractionated palliative radiation (Days -2, -1, and Day 0 prior to Cycle 1), patients will receive tremelimumab (75 mg IV infusion) on Day 1 for 4 cycles (in combination with durvalumab).
arm group label: durvalumab and tremelimumab
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Norman Wolmark, MD
role: Principal Investigator
affiliation: NSABP Foundation Inc
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
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country: United States
citation: Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.
PMID: 19097774
responsible party type: Sponsor
mesh term: Colorectal Neoplasms
mesh term: Durvalumab
mesh term: Tremelimumab
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