<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/NCT02260440</url>
  </required_header>
  <id_info>
    <org_study_id>14-118</org_study_id>
    <nct_id>NCT02260440</nct_id>
  </id_info>
  <brief_title>A Phase 2 Study of Pembrolizumab (MK-3475) in Combination With Azacitidine in Subjects With Chemo-refractory Metastatic Colorectal Cancer</brief_title>
  <official_title>A Phase 2 Study of Pembrolizumab (MK-3475) in Combination With Azacitidine in Subjects With Chemo-refractory Metastatic Colorectal Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Anuradha Krishnamurthy</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Pittsburgh</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an open label, single-arm, Phase 2 trial to evaluate the anti-tumor activity, safety,&#xD;
      and tolerability of Pembrolizumab in combination with azacitidine in subjects with&#xD;
      chemo-refractory mCRC without any further standard treatment options&#xD;
&#xD;
      Dosage and regimen for all study periods&#xD;
&#xD;
        -  Pembrolizumab will be given at 200 mg every 21 days.&#xD;
&#xD;
        -  Azacitidine will be given at 100 mg daily subcutaneous injection on days 1-5 every 21&#xD;
           days.&#xD;
&#xD;
      The first assessment of tumor response will be performed after cycle 3 (9 weeks), and&#xD;
      thereafter approximately every 9 weeks, every 3 cycles of therapy. The modified RECIST 1.1&#xD;
      will be used to establish disease response or progression.&#xD;
&#xD;
      All patients will be evaluated and graded for adverse events according to the NCI Common&#xD;
      Terminology for Adverse Events, version 4.0 (NCI-CTCAE).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>January 2015</start_date>
  <completion_date type="Actual">September 2017</completion_date>
  <primary_completion_date type="Actual">March 2016</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>Objective Response Rate (ORR)</measure>
    <time_frame>Up to 14 months</time_frame>
    <description>The objective response rate is estimated by the proportion (percentage) of participants with the best response of complete response (CR), or partial response (PR) by RECIST 1.1 criteria, with corresponding exact 95% confidence limits being reported. Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), &gt;=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival (PFS)</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Progression-free Survival (PFS) (median) was determined using the number of months measured from the initial date of treatment to the date of documented progression, or the date of death (in the absence of progression) of participants. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Overall Survival (OS) (median) was determined using the number of months measured from the initial date of treatment to the recorded date of death of participants.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">31</enrollment>
  <condition>Metastatic Colorectal Cancer</condition>
  <arm_group>
    <arm_group_label>Pembrolizumab and Azacitidine Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>9 cycles&#xD;
Pembrolizumab will be given at 200 mg every 21 days.&#xD;
Azacitidine will be given at 100 mg daily subcutaneous injection on days 1-5 every 21 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>Pembrolizumab will be given at 200 mg every 21 days</description>
    <arm_group_label>Pembrolizumab and Azacitidine Arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Azacitidine</intervention_name>
    <description>Azacitidine will be given at 100 mg daily subcutaneous injection on days 1-5 every 21 days.</description>
    <arm_group_label>Pembrolizumab and Azacitidine Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Be willing and able to provide written informed consent/assent for the trial.&#xD;
&#xD;
          2. Be 18 years of age or older on day of signing informed consent.&#xD;
&#xD;
          3. The diagnosis of mCRC will be based on histologic or cytologic confirmation.&#xD;
&#xD;
          4. Have mCRC that has been previously treated with currently approved standard therapies.&#xD;
&#xD;
          5. Have measurable disease based on RECIST 1.1.&#xD;
&#xD;
          6. At least 1 of the tumor sites must be amenable to core needle biopsy and this may not&#xD;
             be the site of disease used to measure antitumor response. Patient must agree to this&#xD;
             mandatory biopsy.&#xD;
&#xD;
          7. Have a performance status of 0 or 1 on the ECOG Performance Scale.&#xD;
&#xD;
          8. Demonstrate adequate organ function, all screening labs should be performed within 14&#xD;
             days of treatment initiation.&#xD;
&#xD;
          9. Female subject of childbearing potential should have a negative urine or serum&#xD;
             pregnancy within 72 hours prior to receiving the first dose of study medication. If&#xD;
             the urine test is positive or cannot be confirmed as negative, a serum pregnancy test&#xD;
             will be required.&#xD;
&#xD;
         10. Female subjects of childbearing potential should be willing to use 2 methods of birth&#xD;
             control or be surgically sterile, or abstain from heterosexual activity for the course&#xD;
             of the study through 120 days after the last dose of study medication. Subjects of&#xD;
             childbearing potential are those who have not been surgically sterilized or have not&#xD;
             been free from menses for &gt; 1 year.&#xD;
&#xD;
         11. Male subjects should agree to use an adequate method of contraception starting with&#xD;
             the first dose of study therapy through 120 days after the last dose of study therapy.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Is currently participating in or has participated in a study of an investigational&#xD;
             agent or using an investigational device within 4 weeks of the first dose of&#xD;
             treatment.&#xD;
&#xD;
          2. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any&#xD;
             other form of immunosuppressive therapy within 7 days prior to the first dose of trial&#xD;
             treatment.&#xD;
&#xD;
          3. Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not&#xD;
             recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents&#xD;
             administered more than 4 weeks earlier.&#xD;
&#xD;
          4. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy&#xD;
             within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at&#xD;
             baseline) from adverse events due to a previously administered agent.&#xD;
&#xD;
             - Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may&#xD;
             qualify for the study.&#xD;
&#xD;
          5. Has a known additional malignancy that is progressing or requires active treatment.&#xD;
             Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the&#xD;
             skin, or in situ cervical cancer that has undergone potentially curative therapy..&#xD;
&#xD;
          6. Has extensive metastatic tumor burden in the liver with serum albumin &lt;3.0 g/dL.&#xD;
&#xD;
          7. Has known renal tubular acidosis with serum bicarbonate &lt;20 mEq/L.&#xD;
&#xD;
          8. Has a known hypersensitivity to azacitidine or mannitol.&#xD;
&#xD;
          9. Has known active central nervous system (CNS) metastases and/or carcinomatous&#xD;
             meningitis. Subjects with previously treated brain metastases may participate provided&#xD;
             they are stable (without evidence of progression by imaging for at least four weeks&#xD;
             prior to the first dose of trial treatment and any neurologic symptoms have returned&#xD;
             to baseline), have no evidence of new or enlarging brain metastases, and are not using&#xD;
             steroids for at least 7 days prior to trial treatment.&#xD;
&#xD;
         10. Has an active autoimmune disease requiring systemic treatment within the past 3 months&#xD;
             or a documented history of clinically severe autoimmune disease, or a syndrome that&#xD;
             requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or&#xD;
             resolved childhood asthma/atopy would be an exception to this rule. Subjects that&#xD;
             require intermittent use of bronchodilators or local steroid injections would not be&#xD;
             excluded from the study. Subjects with hypothyroidism stable on hormone replacement or&#xD;
             Sjorgen's syndrome will not be excluded from the study.&#xD;
&#xD;
         11. Has evidence of interstitial lung disease or active, non-infectious pneumonitis.&#xD;
&#xD;
         12. Has an active infection requiring systemic therapy.&#xD;
&#xD;
         13. Has a history or current evidence of any condition, therapy, or laboratory abnormality&#xD;
             that might confound the results of the trial, interfere with the subject's&#xD;
             participation for the full duration of the trial, or is not in the best interest of&#xD;
             the subject to participate, in the opinion of the treating investigator.&#xD;
&#xD;
         14. Has known psychiatric or substance abuse disorders that would interfere with&#xD;
             cooperation with the requirements of the trial.&#xD;
&#xD;
         15. Is pregnant or breastfeeding, or expecting to conceive or father children within the&#xD;
             projected duration of the trial, starting with the pre-screening or screening visit&#xD;
             through 120 days after the last dose of trial treatment.&#xD;
&#xD;
         16. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or&#xD;
             anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including&#xD;
             ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation&#xD;
             or checkpoint pathways).&#xD;
&#xD;
         17. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).&#xD;
&#xD;
         18. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA&#xD;
             [qualitative] is detected).&#xD;
&#xD;
        Has received a live vaccine within 30 days prior to the first dose of trial treatment.&#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>Anuradha Krishnamurthy, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pittsburgh</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hillman Cancer Center</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2019</verification_date>
  <study_first_submitted>October 6, 2014</study_first_submitted>
  <study_first_submitted_qc>October 6, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 9, 2014</study_first_posted>
  <results_first_submitted>April 10, 2017</results_first_submitted>
  <results_first_submitted_qc>April 10, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">May 16, 2017</results_first_posted>
  <last_update_submitted>September 9, 2019</last_update_submitted>
  <last_update_submitted_qc>September 9, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">September 17, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Pittsburgh</investigator_affiliation>
    <investigator_full_name>Anuradha Krishnamurthy</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <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>Pembrolizumab</mesh_term>
    <mesh_term>Azacitidine</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Pembrolizumab and Azacitidine</title>
          <description>200 mg of Pembrolizumab was administered intravenously over 30 minutes on Day 1 of every 21 day cycle. 100 mg of Azacitidine was given daily via subcutaneous injection on days 1-5 every 21 days.&#xD;
Treatment continued for 9 cycles (about 27 weeks) or until there was an evidence of progression of disease (PD) or unacceptable toxicity before the completion of the planned 9 cycles.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="31"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="31"/>
              </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>Pembrolizumab and Azacitidine</title>
          <description>200 mg of Pembrolizumab was administered intravenously over 30 minutes on Day 1 of every 21 day cycle. 100 mg of Azacitidine was given daily via subcutaneous injection on days 1-5 every 21 days.&#xD;
Treatment continued for 9 cycles (about 27 weeks) or until there was an evidence of progression of disease (PD) or unacceptable toxicity before the completion of the planned 9 cycles.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="31"/>
          </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="61" lower_limit="30" upper_limit="79"/>
                  </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="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Objective Response Rate (ORR)</title>
        <description>The objective response rate is estimated by the proportion (percentage) of participants with the best response of complete response (CR), or partial response (PR) by RECIST 1.1 criteria, with corresponding exact 95% confidence limits being reported. Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), &gt;=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.</description>
        <time_frame>Up to 14 months</time_frame>
        <population>Participants who received at least one dose of study therapy (median, 3 cycles; range, 1-8).</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab and Azacitidine</title>
            <description>200 mg of Pembrolizumab was administered intravenously over 30 minutes on Day 1 of every 21 day cycle. 100 mg of Azacitidine was given daily via subcutaneous injection on days 1-5 every 21 days.&#xD;
Treatment continued for 9 cycles (about 27 weeks) or until there was an evidence of progression of disease (PD) or unacceptable toxicity before the completion of the planned 9 cycles.</description>
          </group>
        </group_list>
        <measure>
          <title>Objective Response Rate (ORR)</title>
          <description>The objective response rate is estimated by the proportion (percentage) of participants with the best response of complete response (CR), or partial response (PR) by RECIST 1.1 criteria, with corresponding exact 95% confidence limits being reported. Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), &gt;=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.</description>
          <population>Participants who received at least one dose of study therapy (median, 3 cycles; range, 1-8).</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3" lower_limit="1" upper_limit="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression-free Survival (PFS)</title>
        <description>Progression-free Survival (PFS) (median) was determined using the number of months measured from the initial date of treatment to the date of documented progression, or the date of death (in the absence of progression) of participants. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.</description>
        <time_frame>Up to 2 years</time_frame>
        <population>Participants who received at least one dose of study therapy (median, 3 cycles; range, 1-8).</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab and Azacitidine</title>
            <description>200 mg of Pembrolizumab was administered intravenously over 30 minutes on Day 1 of every 21 day cycle. 100 mg of Azacitidine was given daily via subcutaneous injection on days 1-5 every 21 days.&#xD;
Treatment continued for 9 cycles (about 27 weeks) or until there was an evidence of progression of disease (PD) or unacceptable toxicity before the completion of the planned 9 cycles.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-free Survival (PFS)</title>
          <description>Progression-free Survival (PFS) (median) was determined using the number of months measured from the initial date of treatment to the date of documented progression, or the date of death (in the absence of progression) of participants. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.</description>
          <population>Participants who received at least one dose of study therapy (median, 3 cycles; range, 1-8).</population>
          <units>months</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="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.1" lower_limit="1.8" upper_limit="2.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival (OS)</title>
        <description>Overall Survival (OS) (median) was determined using the number of months measured from the initial date of treatment to the recorded date of death of participants.</description>
        <time_frame>Up to 2 years</time_frame>
        <population>Participants who received at least one dose of study therapy (median, 3 cycles; range, 1-8).</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab and Azacitidine</title>
            <description>200 mg of Pembrolizumab was administered intravenously over 30 minutes on Day 1 of every 21 day cycle. 100 mg of Azacitidine was given daily via subcutaneous injection on days 1-5 every 21 days.&#xD;
Treatment continued for 9 cycles (about 27 weeks) or until there was an evidence of progression of disease (PD) or unacceptable toxicity before the completion of the planned 9 cycles.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS)</title>
          <description>Overall Survival (OS) (median) was determined using the number of months measured from the initial date of treatment to the recorded date of death of participants.</description>
          <population>Participants who received at least one dose of study therapy (median, 3 cycles; range, 1-8).</population>
          <units>months</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="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.2" lower_limit="3.5" upper_limit="8.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Pembrolizumab and Azacitidine</title>
          <description>200 mg of Pembrolizumab was administered intravenously over 30 minutes on Day 1 of every 21 day cycle. 100 mg of Azacitidine was given daily via subcutaneous injection on days 1-5 every 21 days.&#xD;
Treatment continued for 9 cycles (about 27 weeks) or until there was an evidence of progression of disease (PD) or unacceptable toxicity before the completion of the planned 9 cycles.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="30"/>
              </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="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Death NOS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatobiliary disorders - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </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="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Generalized muscle weakness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Lethargy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Stroke</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Confusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hematuria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Renal and urinary disorders - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </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="30" subjects_at_risk="30"/>
              </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="18" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Sinus bradycardia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorders - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>General disorders and administration site conditions - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="30"/>
              </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="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypophosphatemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Metabolism and nutrition disorders - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypernatremia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Musculoskeletal and connective tissue disorder - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="30"/>
              </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>Anuradha Krishnamurthy, MD</name_or_title>
      <organization>UPMC Hillman Cancer Center</organization>
      <phone>412-623-3283</phone>
      <email>krishnamurthya2@upmc.edu</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/NCT02260440
org study id: 14-118
nct id: NCT02260440
lead sponsor: 
collaborator: 
has dmc: Yes
This is an open label, single-arm, Phase 2 trial to evaluate the anti-tumor activity, safety,
      and tolerability of Pembrolizumab in combination with azacitidine in subjects with
      chemo-refractory mCRC without any further standard treatment options

      Dosage and regimen for all study periods

        -  Pembrolizumab will be given at 200 mg every 21 days.

        -  Azacitidine will be given at 100 mg daily subcutaneous injection on days 1-5 every 21
           days.

      The first assessment of tumor response will be performed after cycle 3 (9 weeks), and
      thereafter approximately every 9 weeks, every 3 cycles of therapy. The modified RECIST 1.1
      will be used to establish disease response or progression.

      All patients will be evaluated and graded for adverse events according to the NCI Common
      Terminology for Adverse Events, version 4.0 (NCI-CTCAE).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective Response Rate (ORR)
time frame: Up to 14 months
description: The objective response rate is estimated by the proportion (percentage) of participants with the best response of complete response (CR), or partial response (PR) by RECIST 1.1 criteria, with corresponding exact 95% confidence limits being reported. Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
measure: Progression-free Survival (PFS)
time frame: Up to 2 years
description: Progression-free Survival (PFS) (median) was determined using the number of months measured from the initial date of treatment to the date of documented progression, or the date of death (in the absence of progression) of participants. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
measure: Overall Survival (OS)
time frame: Up to 2 years
description: Overall Survival (OS) (median) was determined using the number of months measured from the initial date of treatment to the recorded date of death of participants.
arm group label: Pembrolizumab and Azacitidine Arm
arm group type: Experimental
description: 9 cycles
Pembrolizumab will be given at 200 mg every 21 days.
Azacitidine will be given at 100 mg daily subcutaneous injection on days 1-5 every 21 days.
intervention type: Drug
intervention name: Pembrolizumab
description: Pembrolizumab will be given at 200 mg every 21 days
arm group label: Pembrolizumab and Azacitidine Arm
intervention type: Drug
intervention name: Azacitidine
description: Azacitidine will be given at 100 mg daily subcutaneous injection on days 1-5 every 21 days.
arm group label: Pembrolizumab and Azacitidine Arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Anuradha Krishnamurthy, MD
role: Principal Investigator
affiliation: University of Pittsburgh
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of Pittsburgh
investigator full name: Anuradha Krishnamurthy
investigator title: Assistant Professor
mesh term: Colorectal Neoplasms
mesh term: Pembrolizumab
mesh term: Azacitidine
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 