<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/NCT02227667</url>
  </required_header>
  <id_info>
    <org_study_id>14-109</org_study_id>
    <nct_id>NCT02227667</nct_id>
  </id_info>
  <brief_title>Evaluate the Efficacy of MEDI4736 in Immunological Subsets of Advanced Colorectal Cancer</brief_title>
  <official_title>Phase II Study to Evaluate the Efficacy of MEDI4736 in Immunological Subsets of Advanced Colorectal Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Memorial Sloan Kettering Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>MedImmune LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Memorial Sloan Kettering Cancer Center</source>
  <brief_summary>
    <textblock>
      The purpose of this study is to find out what effects, good and/or bad, MEDI4736 has on the&#xD;
      patient and cancer.&#xD;
&#xD;
      MEDI4736 is a type of medication called an antibody. Antibodies are normal proteins in the&#xD;
      body that help fight infections and possibly cancer. MEDI4736 is a special type of an&#xD;
      antibody produced in a laboratory. MEDI4736 works by blocking a specific protein called the&#xD;
      Programmed Death Ligand-1 (PDL-1), located on tumor cells.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 2, 2014</start_date>
  <completion_date type="Actual">June 29, 2020</completion_date>
  <primary_completion_date type="Actual">June 29, 2020</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>Best Response Rate</measure>
    <time_frame>2 years</time_frame>
    <description>according to RECIST 1.1.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Evaluated for Toxicities to Determine Safety</measure>
    <time_frame>2 years</time_frame>
    <description>Subjects will be evaluated for occurrence of AEs at each visit. Events will be characterized and reported. Safety will also be monitored by performing physical exams and routine laboratory procedures. Terminology Criteria for Adverse Events&quot; V4.0 (CTCAE).</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">16</enrollment>
  <condition>Advanced Colorectal Cancer</condition>
  <arm_group>
    <arm_group_label>Patients with Advanced Colorectal Cancer</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This will be a Simon two-stage design, single arm, phase II study. All subjects will receive MEDI4736 via IV infusion. Subjects will continue treatment for 12 months, or until progression of disease, initiation of alternative cancer therapy, unacceptable toxicity, or other reasons to discontinue treatment occur. Following the 12-month treatment period, subjects without evidence for progressive disease or other reason to discontinue treatment will be monitored without further treatment. Upon evidence of PD (with or without confirmation according to RECIST 1.1) during the monitoring period, administration of MEDI4736 may resume at the Q2W schedule, for up to another 12 months. The same treatment guidelines followed during the initial 12-month treatment period will be followed during the retreatment period, including the same dose and frequency of treatments and the same schedule of assessments.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MEDI4736</intervention_name>
    <description>Patients will be seen the day of administration of MEDI4736. A medical history, with particular reference to toxicities, including medication review, and physical examination will be conducted at each treatment visit.</description>
    <arm_group_label>Patients with Advanced Colorectal Cancer</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Written informed consent obtained.&#xD;
&#xD;
          -  Histologically- or cytologically- confirmed CRC.&#xD;
&#xD;
          -  Microsatelite-high colorectal cancer (also known as MSI-H, DNA mismatch repair&#xD;
             deficient, or sometimes Lynch syndrome); or increased Tumor-Infiltrating Lymphocytes&#xD;
             in an archived tumor specimen or fresh biopsy.&#xD;
&#xD;
          -  Locally advanced or metastatic CRC&#xD;
&#xD;
          -  Subjects have received two or more standard available therapies known to prolong&#xD;
             survival and for which they would be considered eligible. At a minimum, such therapies&#xD;
             should include regimens containing oxaliplatin and irinotecan in combination with a&#xD;
             fluoropyrimidine (e.g., FOLFOX and FOLFIRI or their variants).&#xD;
&#xD;
          -  Age ≥ 18 years at time of study entry.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) status of 0 or 1&#xD;
&#xD;
          -  Adequate organ and marrow function as defined below:&#xD;
&#xD;
          -  Absolute neutrophil count ≥ 1,500/mm3.&#xD;
&#xD;
          -  Platelet count ≥ 90,000/mm3.&#xD;
&#xD;
          -  AST and ALT ≤ 3 × institutional upper limit of normal (ULN) or ≤ 5 × ULN for subjects&#xD;
             with liver metastases.&#xD;
&#xD;
          -  Bilirubin ≤ 1.5 × ULN or ≤ 3 × ULN for subjects with documented/suspected Gilbert's&#xD;
             disease.&#xD;
&#xD;
          -  Serum creatinine ≤ 1.5 x ULN;&#xD;
&#xD;
          -  Radiographically measurable disease per RECIST 1.1.&#xD;
&#xD;
          -  Life expectancy ≥ 16 weeks.&#xD;
&#xD;
          -  Willingness to provide consent for use of archived tissue for research purposes.&#xD;
&#xD;
          -  Subjects will be required to agree to a biopsy performed at baseline and again at week&#xD;
             8 of the study in order to be eligible for enrollment in stage 1 of the study&#xD;
&#xD;
          -  Females of childbearing potential who are sexually active with a nonsterilized male&#xD;
             partner must use 2 methods of effective contraception from screening, and must agree&#xD;
             to continue using such precautions for 90 days after the final dose of investigational&#xD;
             product; cessation of birth control after this point should be discussed with a&#xD;
             responsible physician. Periodic abstinence, the rhythm method, and the withdrawal&#xD;
             method are not acceptable methods of birth control.&#xD;
&#xD;
          -  Females of childbearing potential are defined as those who are not surgically sterile&#xD;
             (ie, bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or&#xD;
             postmenopausal (defined as 12 months with no menses without an alternative medical&#xD;
             cause).&#xD;
&#xD;
          -  Subjects must use 2 acceptable methods of effective contraception as described in&#xD;
             below.&#xD;
&#xD;
          -  Nonsterilized males who are sexually active with a female partner of childbearing&#xD;
             potential must use 2 acceptable methods of effective contraception from Day 1 and for&#xD;
             90 days after receipt of the final dose of investigational product.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Anticancer therapy, monoclonal antibody or major surgery within 4 weeks prior to the&#xD;
             first dose of MEDI4736.&#xD;
&#xD;
          -  Concurrent use of hormones for non-cancer-related conditions (e.g., insulin for&#xD;
             diabetes and hormone replacement therapy) is acceptable.&#xD;
&#xD;
          -  Any prior Grade ≥ 3 irAE while receiving immunotherapy (including anti-CTLA-4 or&#xD;
             anti-CD137 MAb) or any unresolved irAE of any grade (controlled irAE endocrinopathies&#xD;
             are allowed).&#xD;
&#xD;
          -  Prior exposure to any anti-PD-1 or anti-PD-L1 antibody.&#xD;
&#xD;
          -  Current or prior use of immunosuppressive medication within 28 days before the first&#xD;
             dose of MEDI4736, 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;
          -  Any unresolved toxicity CTCAE &gt;Grade 2 from previous anti-cancer therapy.&#xD;
&#xD;
          -  Active autoimmune disease within the past 2 years, except for mild conditions not&#xD;
             requiring systemic treatment, such as vitiligo.&#xD;
&#xD;
          -  Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer&#xD;
             treatment. NOTE: Local treatment of isolated lesions, excluding target lesions, for&#xD;
             palliative intent is acceptable (e.g., by local ablation, surgery or radiotherapy).&#xD;
&#xD;
          -  Active or prior documented inflammatory bowel disease (e.g., Crohn's disease,&#xD;
             irritable bowel syndrome, ulcerative colitis).&#xD;
&#xD;
          -  Receipt of radiation therapy within 4 weeks prior to starting investigational product,&#xD;
             or limited field of radiation for palliation within 2 weeks of the first dose of&#xD;
             investigational product.&#xD;
&#xD;
          -  Known allergy or reaction to any component of the MEDI4736 formulation or its&#xD;
             excipients.&#xD;
&#xD;
          -  Known central nervous system (CNS) metastases requiring treatment, such as surgery,&#xD;
             radiation or steroids.&#xD;
&#xD;
          -  Known history of confirmed primary immunodeficiency.&#xD;
&#xD;
          -  History of organ transplant requiring therapeutic immunosuppression.&#xD;
&#xD;
          -  Other malignancy within 3 years, except for noninvasive malignancies such as cervical&#xD;
             carcinoma in situ (CIS), non-melanomatous carcinoma of the skin or ductal carcinoma in&#xD;
             situ (DCIS) of the breast that has/have been surgically cured, or prior malignancy&#xD;
             considered by the investigator to be of low likelihood for recurrence.&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable&#xD;
             angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active&#xD;
             bleeding diatheses including any patient known to have active hepatitis B, hepatitis C&#xD;
             or human immunodeficiency virus (HIV), or psychiatric illness/social situations that&#xD;
             would limit compliance with study requirements or compromise the ability of the&#xD;
             patient to give written informed consent.&#xD;
&#xD;
          -  Women who are pregnant, breast-feeding or male or female patients of reproductive&#xD;
             potential who are not employing an effective method of birth control.&#xD;
&#xD;
          -  Any other condition(s) that, in the opinion of the investigator, would interfere with&#xD;
             evaluation of the investigational product or interpretation of subject safety or study&#xD;
             results.&#xD;
&#xD;
          -  Subjects who are known to be HIV positive.&#xD;
&#xD;
          -  Receipt of live attenuated vaccination within 30 days prior to receiving MEDI4736&#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>Neil Segal, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Memorial Sloan Kettering Cancer Center</affiliation>
  </overall_official>
  <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_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mskcc.org/</url>
    <description>Memorial Sloan Kettering Cancer Center</description>
  </link>
  <verification_date>May 2021</verification_date>
  <study_first_submitted>July 17, 2014</study_first_submitted>
  <study_first_submitted_qc>August 27, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 28, 2014</study_first_posted>
  <results_first_submitted>May 25, 2021</results_first_submitted>
  <results_first_submitted_qc>May 25, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">June 18, 2021</results_first_posted>
  <last_update_submitted>May 25, 2021</last_update_submitted>
  <last_update_submitted_qc>May 25, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 18, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>MEDI4736</keyword>
  <keyword>14-109</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>
  </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 9, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/67/NCT02227667/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Patients With Advanced Colorectal Cancer</title>
          <description>This will be a Simon two-stage design, single arm, phase II study. All subjects will receive MEDI4736 via IV infusion. Subjects will continue treatment for 12 months, or until progression of disease, initiation of alternative cancer therapy, unacceptable toxicity, or other reasons to discontinue treatment occur. Following the 12-month treatment period, subjects without evidence for progressive disease or other reason to discontinue treatment will be monitored without further treatment. Upon evidence of PD (with or without confirmation according to RECIST 1.1) during the monitoring period, administration of MEDI4736 may resume at the Q2W schedule, for up to another 12 months. The same treatment guidelines followed during the initial 12-month treatment period will be followed during the retreatment period, including the same dose and frequency of treatments and the same schedule of assessments.&#xD;
MEDI4736: Patients will be seen the day of administration of MEDI4736. A medical history, with particular reference to toxicities, including medication review, and physical examination will be conducted at each treatment visit.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Patients With Advanced Colorectal Cancer</title>
          <description>This will be a Simon two-stage design, single arm, phase II study. All subjects will receive MEDI4736 via IV infusion. Subjects will continue treatment for 12 months, or until progression of disease, initiation of alternative cancer therapy, unacceptable toxicity, or other reasons to discontinue treatment occur. Following the 12-month treatment period, subjects without evidence for progressive disease or other reason to discontinue treatment will be monitored without further treatment. Upon evidence of PD (with or without confirmation according to RECIST 1.1) during the monitoring period, administration of MEDI4736 may resume at the Q2W schedule, for up to another 12 months. The same treatment guidelines followed during the initial 12-month treatment period will be followed during the retreatment period, including the same dose and frequency of treatments and the same schedule of assessments.&#xD;
MEDI4736: Patients will be seen the day of administration of MEDI4736. A medical history, with particular reference to toxicities, including medication review, and physical examination will be conducted at each treatment visit.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="16"/>
          </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="57" lower_limit="24" upper_limit="86"/>
                  </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="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Best Response Rate</title>
        <description>according to RECIST 1.1.</description>
        <time_frame>2 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Patients With Advanced Colorectal Cancer</title>
            <description>This will be a Simon two-stage design, single arm, phase II study. All subjects will receive MEDI4736 via IV infusion. Subjects will continue treatment for 12 months, or until progression of disease, initiation of alternative cancer therapy, unacceptable toxicity, or other reasons to discontinue treatment occur. Following the 12-month treatment period, subjects without evidence for progressive disease or other reason to discontinue treatment will be monitored without further treatment. Upon evidence of PD (with or without confirmation according to RECIST 1.1) during the monitoring period, administration of MEDI4736 may resume at the Q2W schedule, for up to another 12 months. The same treatment guidelines followed during the initial 12-month treatment period will be followed during the retreatment period, including the same dose and frequency of treatments and the same schedule of assessments.&#xD;
MEDI4736: Patients will be seen the day of administration of MEDI4736. A medical history, with particular reference to toxicities, including medication review, and physical examination will be conducted at each treatment visit.</description>
          </group>
        </group_list>
        <measure>
          <title>Best Response Rate</title>
          <description>according to RECIST 1.1.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Complete Response</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Partial Response</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Stable Response</title>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Progression of Disease</title>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Entered</title>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Evaluated for Toxicities to Determine Safety</title>
        <description>Subjects will be evaluated for occurrence of AEs at each visit. Events will be characterized and reported. Safety will also be monitored by performing physical exams and routine laboratory procedures. Terminology Criteria for Adverse Events&quot; V4.0 (CTCAE).</description>
        <time_frame>2 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Patients With Advanced Colorectal Cancer</title>
            <description>This will be a Simon two-stage design, single arm, phase II study. All subjects will receive MEDI4736 via IV infusion. Subjects will continue treatment for 12 months, or until progression of disease, initiation of alternative cancer therapy, unacceptable toxicity, or other reasons to discontinue treatment occur. Following the 12-month treatment period, subjects without evidence for progressive disease or other reason to discontinue treatment will be monitored without further treatment. Upon evidence of PD (with or without confirmation according to RECIST 1.1) during the monitoring period, administration of MEDI4736 may resume at the Q2W schedule, for up to another 12 months. The same treatment guidelines followed during the initial 12-month treatment period will be followed during the retreatment period, including the same dose and frequency of treatments and the same schedule of assessments.&#xD;
MEDI4736: Patients will be seen the day of administration of MEDI4736. A medical history, with particular reference to toxicities, including medication review, and physical examination will be conducted at each treatment visit.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Evaluated for Toxicities to Determine Safety</title>
          <description>Subjects will be evaluated for occurrence of AEs at each visit. Events will be characterized and reported. Safety will also be monitored by performing physical exams and routine laboratory procedures. Terminology Criteria for Adverse Events&quot; V4.0 (CTCAE).</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>2 years</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Patients With Advanced Colorectal Cancer</title>
          <description>This will be a Simon two-stage design, single arm, phase II study. All subjects will receive MEDI4736 via IV infusion. Subjects will continue treatment for 12 months, or until progression of disease, initiation of alternative cancer therapy, unacceptable toxicity, or other reasons to discontinue treatment occur. Following the 12-month treatment period, subjects without evidence for progressive disease or other reason to discontinue treatment will be monitored without further treatment. Upon evidence of PD (with or without confirmation according to RECIST 1.1) during the monitoring period, administration of MEDI4736 may resume at the Q2W schedule, for up to another 12 months. The same treatment guidelines followed during the initial 12-month treatment period will be followed during the retreatment period, including the same dose and frequency of treatments and the same schedule of assessments.&#xD;
MEDI4736: Patients will be seen the day of administration of MEDI4736. A medical history, with particular reference to toxicities, including medication review, and physical examination will be conducted at each treatment visit.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Small intestinal obstruction</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Death NOS</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Gait disturbance</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Enterocolitis infectious</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
              </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="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Flank pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Neoplasms ben/mal/unk (inc cyst/polyp) Other, spec</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Tremor</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
              </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="16" subjects_at_risk="16"/>
              </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="2" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blurred vision</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Edema limbs</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Gait disturbance</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Rash pustular</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Tremor</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Ataxia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Nervous system disorders - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Peripheral motor neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Urinary frequency</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Sore throat</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </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="5" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Rash acneiform</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hot flashes</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Neil Segal, MD, PhD</name_or_title>
      <organization>Memorial Sloan Kettering Cancer Center</organization>
      <phone>646-888-4187</phone>
      <email>segaln@mskcc.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/NCT02227667
org study id: 14-109
nct id: NCT02227667
lead sponsor: 
collaborator: 
collaborator: 
The purpose of this study is to find out what effects, good and/or bad, MEDI4736 has on the
      patient and cancer.

      MEDI4736 is a type of medication called an antibody. Antibodies are normal proteins in the
      body that help fight infections and possibly cancer. MEDI4736 is a special type of an
      antibody produced in a laboratory. MEDI4736 works by blocking a specific protein called the
      Programmed Death Ligand-1 (PDL-1), located on tumor cells.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Best Response Rate
time frame: 2 years
description: according to RECIST 1.1.
measure: Number of Participants Evaluated for Toxicities to Determine Safety
time frame: 2 years
description: Subjects will be evaluated for occurrence of AEs at each visit. Events will be characterized and reported. Safety will also be monitored by performing physical exams and routine laboratory procedures. Terminology Criteria for Adverse Events" V4.0 (CTCAE).
arm group label: Patients with Advanced Colorectal Cancer
arm group type: Experimental
description: This will be a Simon two-stage design, single arm, phase II study. All subjects will receive MEDI4736 via IV infusion. Subjects will continue treatment for 12 months, or until progression of disease, initiation of alternative cancer therapy, unacceptable toxicity, or other reasons to discontinue treatment occur. Following the 12-month treatment period, subjects without evidence for progressive disease or other reason to discontinue treatment will be monitored without further treatment. Upon evidence of PD (with or without confirmation according to RECIST 1.1) during the monitoring period, administration of MEDI4736 may resume at the Q2W schedule, for up to another 12 months. The same treatment guidelines followed during the initial 12-month treatment period will be followed during the retreatment period, including the same dose and frequency of treatments and the same schedule of assessments.
intervention type: Drug
intervention name: MEDI4736
description: Patients will be seen the day of administration of MEDI4736. A medical history, with particular reference to toxicities, including medication review, and physical examination will be conducted at each treatment visit.
arm group label: Patients with Advanced Colorectal Cancer
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Neil Segal, MD, PhD
role: Principal Investigator
affiliation: Memorial Sloan Kettering Cancer Center
facility: 
country: United States
url: http://www.mskcc.org/
description: Memorial Sloan Kettering Cancer Center
responsible party type: Sponsor
mesh term: Colorectal Neoplasms
mesh term: Durvalumab
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 