<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/NCT03824704</url>
  </required_header>
  <id_info>
    <org_study_id>CO-338-097</org_study_id>
    <nct_id>NCT03824704</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate Rucaparib in Combination With Nivolumab in Patients With Selected Solid Tumors (ARIES)</brief_title>
  <official_title>A Phase 2, Open-label Study to Evaluate Rucaparib in Combination With Nivolumab in Patients With Selected Solid Tumors (ARIES)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>pharmaand GmbH</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Bristol-Myers Squibb</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Foundation Medicine</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>pharmaand GmbH</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an open label Phase 2, 2-stage, 2-cohort study to evaluate rucaparib in combination&#xD;
      with nivolumab in patients with high-grade serous or endometroid ovarian cancer.&#xD;
&#xD;
      Patients entering the following cohorts must have BRCA mutational status confirmed by a&#xD;
      central lab:&#xD;
&#xD;
        -  Cohort A1: No BRCA mutation in tumor; high level of LOH (loss of heterozygosity)&#xD;
&#xD;
        -  Cohort A2: BRCA mutation in tumor&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Sponsor made a business decision to discontinue the study due to low accrual.&#xD;
  </why_stopped>
  <start_date type="Actual">August 23, 2019</start_date>
  <completion_date type="Actual">August 24, 2020</completion_date>
  <primary_completion_date type="Actual">August 24, 2020</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <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) by RECIST v1.1 as Assessed by the Investigator</measure>
    <time_frame>From enrollment until disease progression (up to approximately 2 years)</time_frame>
    <description>Objective response rate (ORR) is defined as the percentage of patients with a best confirmed response of complete response (CR) or partial response (PR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as assessed by the investigator.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The Effect of Rucaparib on the Immune Microenvironment</measure>
    <time_frame>From enrollment to primary completion of study (up to approximately 2 years)</time_frame>
    <description>Change in expression of the immune marker PD-L1 pre and post-rucaparib treatment; Cohort A2 only</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>ORR by RECIST v1.1 and Gynecological Cancer InterGroup (GCIG) Cancer Antigen 125 (CA-125 Criteria)</measure>
    <time_frame>For patients with measurable disease, every 8 weeks after the start of combination treatment for 3 years, then every 24 weeks thereafter until disease progression or up to 25 months. Study data collection expected to last for 2 years.</time_frame>
    <description>Objective Response Rate (ORR) is defined as the percentage of patients with a best confirmed response of complete response (CR) or partial response (PR) by RECIST v1.1 as assessed by the investigator or a confirmed response per Gynecological Cancer InterGroup (GCIG) cancer antigen 125 (CA-125 criteria)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival (PFS)</measure>
    <time_frame>From randomization until disease progression (up to approximately 2 years)</time_frame>
    <description>Progression-Free Survival (PFS) is calculated as 1+ the number of days from the first dose of study drug to disease progression by RECIST, as determined by the investigator or death due to any cause, whichever occurs first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DOR)</measure>
    <time_frame>For patients with measurable disease, every 12 weeks after the start of combination treatment for 3 years, then every 24 weeks thereafter until disease progression. Study data collection expected to last for 2 years</time_frame>
    <description>Duration of response (DOR) for any confirmed RECIST CR or PR measured from the date of the first response until the first date that progressive disease (PD) is documented.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">1</enrollment>
  <condition>Epithelial Ovarian Cancer</condition>
  <condition>Fallopian Tube Cancer</condition>
  <condition>Primary Peritoneal Carcinoma</condition>
  <condition>High Grade Serous Carcinoma</condition>
  <condition>Endometrioid Adenocarcinoma</condition>
  <arm_group>
    <arm_group_label>Cohort A: Ovarian Cancer Cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral rucaparib and Intravenous (IV) nivolumab (combination therapy)&#xD;
Cohort A1&#xD;
Cohort A2</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rucaparib</intervention_name>
    <description>Oral rucaparib will be administered twice daily</description>
    <arm_group_label>Cohort A: Ovarian Cancer Cohort</arm_group_label>
    <other_name>Rubraca</other_name>
    <other_name>CO-338</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nivolumab</intervention_name>
    <description>IV nivolumab will be administered once every 4 weeks</description>
    <arm_group_label>Cohort A: Ovarian Cancer Cohort</arm_group_label>
    <other_name>Opdivo</other_name>
    <other_name>BMS-936558</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        General Inclusion Criteria:&#xD;
&#xD;
          -  ≥ 18 years of age&#xD;
&#xD;
          -  Adequate organ function&#xD;
&#xD;
          -  Life expectancy ≥ 16 weeks&#xD;
&#xD;
          -  Women of childbearing potential must have a negative serum pregnancy test&#xD;
&#xD;
          -  High-grade serous or endometrioid epithelial ovarian, fallopian tube, or primary&#xD;
             peritoneal cancer&#xD;
&#xD;
          -  Received 1 or 2 prior regimens, including ≥ 1 prior platinum-based therapy and have&#xD;
             platinum-sensitive disease&#xD;
&#xD;
          -  Relapsed/progressive disease (confirmed by radiologic assessment)&#xD;
&#xD;
          -  Willing and able to have a biopsy of tumor at screening and after 4 weeks of&#xD;
             treatment.&#xD;
&#xD;
          -  Measurable disease (RECIST v1.1)- Cohort A1 only&#xD;
&#xD;
          -  ECOG performance status of 0 to 1&#xD;
&#xD;
        General Exclusion Criteria&#xD;
&#xD;
          -  Active second malignancy&#xD;
&#xD;
          -  Central nervous system brain metastases&#xD;
&#xD;
          -  Evidence of interstitial lung disease, active pneumonitis, myocarditis, or history of&#xD;
             myocarditis.&#xD;
&#xD;
          -  Active, known or suspected autoimmune disease (eg, autoimmune hepatitis).&#xD;
&#xD;
          -  Condition requiring systemic treatment with either corticosteroids&#xD;
&#xD;
          -  Prior treatment with a PARP inhibitor or immune checkpoint inhibitor.&#xD;
&#xD;
          -  Non-epithelial tumors (pure sarcomas) or ovarian tumors with low malignant potential&#xD;
             (ie, borderline tumors) or mucinous tumors. Mixed Mullerian tumors/carcinosarcomas are&#xD;
             allowed.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kathleen N Moore, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Lead Investigator for Ovarian Cohort A</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Community Cancer Institute</name>
      <address>
        <city>Clovis</city>
        <state>California</state>
        <zip>93611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Health University Medical Center</name>
      <address>
        <city>Savannah</city>
        <state>Georgia</state>
        <zip>31404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Women's Cancer Care</name>
      <address>
        <city>Covington</city>
        <state>Louisiana</state>
        <zip>70433</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stephenson Cancer Center</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Vermont Medical Center</name>
      <address>
        <city>Burlington</city>
        <state>Vermont</state>
        <zip>05041</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>January 21, 2019</study_first_submitted>
  <study_first_submitted_qc>January 30, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 31, 2019</study_first_posted>
  <results_first_submitted>May 19, 2021</results_first_submitted>
  <results_first_submitted_qc>May 19, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">June 15, 2021</results_first_posted>
  <last_update_submitted>June 7, 2023</last_update_submitted>
  <last_update_submitted_qc>June 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 12, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>PARP</keyword>
  <keyword>PARPi</keyword>
  <keyword>PARP inhibitor</keyword>
  <keyword>ARIES</keyword>
  <keyword>Opdivo</keyword>
  <keyword>Rucaparib</keyword>
  <keyword>Nivolumab</keyword>
  <keyword>PD-1</keyword>
  <keyword>BRCA</keyword>
  <keyword>LOH</keyword>
  <keyword>CO-338</keyword>
  <keyword>Immunotherapy</keyword>
  <keyword>BMS-936558</keyword>
  <keyword>Clovis</keyword>
  <keyword>Clovis Oncology</keyword>
  <keyword>Rubraca</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Fallopian Tube Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Ovarian Epithelial</mesh_term>
    <mesh_term>Carcinoma, Endometrioid</mesh_term>
    <mesh_term>Cystadenocarcinoma, Serous</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nivolumab</mesh_term>
    <mesh_term>Rucaparib</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>July 30, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/04/NCT03824704/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>1 subject was recruited from 1 site in the United States. The Sponsor then discontinued the study due to low accrual.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Cohort A: Ovarian Cancer Cohort</title>
          <description>Patients received combination therapy, including oral rucaparib 600mg administered twice daily starting on Cycle 1 Day 1 and intravenous (IV) nivolumab 480mg administered on Day 1 of every 4-week cycle, starting on Cycle 2 Day 1.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Study Terminated by Sponsor</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Cohort A: Ovarian Cancer Cohort</title>
          <description>Patients received combination therapy, including oral rucaparib 600mg administered twice daily starting on Cycle 1 Day 1 and intravenous (IV) nivolumab 480mg administered on Day 1 of every 4-week cycle, starting on Cycle 2 Day 1.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="1"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </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="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </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="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </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="0"/>
                  </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="1"/>
                  </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="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Objective Response Rate (ORR) by RECIST v1.1 as Assessed by the Investigator</title>
        <description>Objective response rate (ORR) is defined as the percentage of patients with a best confirmed response of complete response (CR) or partial response (PR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as assessed by the investigator.</description>
        <time_frame>From enrollment until disease progression (up to approximately 2 years)</time_frame>
        <population>This study was discontinued by the sponsor so no data is available for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort A: Ovarian Cancer Cohort</title>
            <description>Patients received combination therapy, including oral rucaparib 600mg administered twice daily starting on Cycle 1 Day 1 and intravenous (IV) nivolumab 480mg administered on Day 1 of every 4-week cycle, starting on Cycle 2 Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Objective Response Rate (ORR) by RECIST v1.1 as Assessed by the Investigator</title>
          <description>Objective response rate (ORR) is defined as the percentage of patients with a best confirmed response of complete response (CR) or partial response (PR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as assessed by the investigator.</description>
          <population>This study was discontinued by the sponsor so no data is available for this outcome measure.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>The Effect of Rucaparib on the Immune Microenvironment</title>
        <description>Change in expression of the immune marker PD-L1 pre and post-rucaparib treatment; Cohort A2 only</description>
        <time_frame>From enrollment to primary completion of study (up to approximately 2 years)</time_frame>
        <population>This study was discontinued by the sponsor so no data is available for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort A: Ovarian Cancer Cohort</title>
            <description>Patients received combination therapy, including oral rucaparib 600mg administered twice daily starting on Cycle 1 Day 1 and intravenous (IV) nivolumab 480mg administered on Day 1 of every 4-week cycle, starting on Cycle 2 Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>The Effect of Rucaparib on the Immune Microenvironment</title>
          <description>Change in expression of the immune marker PD-L1 pre and post-rucaparib treatment; Cohort A2 only</description>
          <population>This study was discontinued by the sponsor so no data is available for this outcome measure.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>ORR by RECIST v1.1 and Gynecological Cancer InterGroup (GCIG) Cancer Antigen 125 (CA-125 Criteria)</title>
        <description>Objective Response Rate (ORR) is defined as the percentage of patients with a best confirmed response of complete response (CR) or partial response (PR) by RECIST v1.1 as assessed by the investigator or a confirmed response per Gynecological Cancer InterGroup (GCIG) cancer antigen 125 (CA-125 criteria)</description>
        <time_frame>For patients with measurable disease, every 8 weeks after the start of combination treatment for 3 years, then every 24 weeks thereafter until disease progression or up to 25 months. Study data collection expected to last for 2 years.</time_frame>
        <population>This study was discontinued by the sponsor so no data is available for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort A: Ovarian Cancer Cohort</title>
            <description>Patients received combination therapy, including oral rucaparib 600mg administered twice daily starting on Cycle 1 Day 1 and intravenous (IV) nivolumab 480mg administered on Day 1 of every 4-week cycle, starting on Cycle 2 Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>ORR by RECIST v1.1 and Gynecological Cancer InterGroup (GCIG) Cancer Antigen 125 (CA-125 Criteria)</title>
          <description>Objective Response Rate (ORR) is defined as the percentage of patients with a best confirmed response of complete response (CR) or partial response (PR) by RECIST v1.1 as assessed by the investigator or a confirmed response per Gynecological Cancer InterGroup (GCIG) cancer antigen 125 (CA-125 criteria)</description>
          <population>This study was discontinued by the sponsor so no data is available for this outcome measure.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression-free Survival (PFS)</title>
        <description>Progression-Free Survival (PFS) is calculated as 1+ the number of days from the first dose of study drug to disease progression by RECIST, as determined by the investigator or death due to any cause, whichever occurs first.</description>
        <time_frame>From randomization until disease progression (up to approximately 2 years)</time_frame>
        <population>This study was discontinued by the sponsor so no data is available for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort A: Ovarian Cancer Cohort</title>
            <description>Patients received combination therapy, including oral rucaparib 600mg administered twice daily starting on Cycle 1 Day 1 and intravenous (IV) nivolumab 480mg administered on Day 1 of every 4-week cycle, starting on Cycle 2 Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-free Survival (PFS)</title>
          <description>Progression-Free Survival (PFS) is calculated as 1+ the number of days from the first dose of study drug to disease progression by RECIST, as determined by the investigator or death due to any cause, whichever occurs first.</description>
          <population>This study was discontinued by the sponsor so no data is available for this outcome measure.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Response (DOR)</title>
        <description>Duration of response (DOR) for any confirmed RECIST CR or PR measured from the date of the first response until the first date that progressive disease (PD) is documented.</description>
        <time_frame>For patients with measurable disease, every 12 weeks after the start of combination treatment for 3 years, then every 24 weeks thereafter until disease progression. Study data collection expected to last for 2 years</time_frame>
        <population>This study was discontinued by the sponsor so no data is available for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort A: Ovarian Cancer Cohort</title>
            <description>Patients received combination therapy, including oral rucaparib 600mg administered twice daily starting on Cycle 1 Day 1 and intravenous (IV) nivolumab 480mg administered on Day 1 of every 4-week cycle, starting on Cycle 2 Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Response (DOR)</title>
          <description>Duration of response (DOR) for any confirmed RECIST CR or PR measured from the date of the first response until the first date that progressive disease (PD) is documented.</description>
          <population>This study was discontinued by the sponsor so no data is available for this outcome measure.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug.</time_frame>
      <desc>If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class).</desc>
      <group_list>
        <group group_id="E1">
          <title>Cohort A: Ovarian Cancer Cohort</title>
          <description>Patients received combination therapy, including oral rucaparib 600mg administered twice daily starting on Cycle 1 Day 1 and intravenous (IV) nivolumab 480mg administered on Day 1 of every 4-week cycle, starting on Cycle 2 Day 1.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (Unspecified)</default_vocab>
        <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="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (Unspecified)</default_vocab>
        <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="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Adrenal insufficiency</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="4" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="4" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Dsypepsia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="5" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </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" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Tremor</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Cognitive disorder</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hypoaesthesia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Panic attack</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Chronic kidney disease</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Hair texture abnormal</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hot flush</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>Sponsor's agreements with investigators require proposed public disclosures of trial results to be submitted to Sponsor for review prior to publication. Sponsor may request deletion of confidential information or a delay in publication to address intellectual property concerns, but Sponsor may not suppress publication of the trial results indefinitely. Sponsor may request delay of a single-center publication until after the release of a multi-site publication or an agreed upon period of time.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>The Sponsor made a business decision to discontinue the study due to low accrual.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Medical Information Department</name_or_title>
      <organization>Clovis Oncology, Inc.</organization>
      <phone>+1 415 409 7220</phone>
      <email>medinfo@clovisoncology.com</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/NCT03824704
org study id: CO-338-097
nct id: NCT03824704
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is an open label Phase 2, 2-stage, 2-cohort study to evaluate rucaparib in combination
      with nivolumab in patients with high-grade serous or endometroid ovarian cancer.

      Patients entering the following cohorts must have BRCA mutational status confirmed by a
      central lab:

        -  Cohort A1: No BRCA mutation in tumor; high level of LOH (loss of heterozygosity)

        -  Cohort A2: BRCA mutation in tumor
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective Response Rate (ORR) by RECIST v1.1 as Assessed by the Investigator
time frame: From enrollment until disease progression (up to approximately 2 years)
description: Objective response rate (ORR) is defined as the percentage of patients with a best confirmed response of complete response (CR) or partial response (PR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as assessed by the investigator.
measure: The Effect of Rucaparib on the Immune Microenvironment
time frame: From enrollment to primary completion of study (up to approximately 2 years)
description: Change in expression of the immune marker PD-L1 pre and post-rucaparib treatment; Cohort A2 only
measure: ORR by RECIST v1.1 and Gynecological Cancer InterGroup (GCIG) Cancer Antigen 125 (CA-125 Criteria)
time frame: For patients with measurable disease, every 8 weeks after the start of combination treatment for 3 years, then every 24 weeks thereafter until disease progression or up to 25 months. Study data collection expected to last for 2 years.
description: Objective Response Rate (ORR) is defined as the percentage of patients with a best confirmed response of complete response (CR) or partial response (PR) by RECIST v1.1 as assessed by the investigator or a confirmed response per Gynecological Cancer InterGroup (GCIG) cancer antigen 125 (CA-125 criteria)
measure: Progression-free Survival (PFS)
time frame: From randomization until disease progression (up to approximately 2 years)
description: Progression-Free Survival (PFS) is calculated as 1+ the number of days from the first dose of study drug to disease progression by RECIST, as determined by the investigator or death due to any cause, whichever occurs first.
measure: Duration of Response (DOR)
time frame: For patients with measurable disease, every 12 weeks after the start of combination treatment for 3 years, then every 24 weeks thereafter until disease progression. Study data collection expected to last for 2 years
description: Duration of response (DOR) for any confirmed RECIST CR or PR measured from the date of the first response until the first date that progressive disease (PD) is documented.
arm group label: Cohort A: Ovarian Cancer Cohort
arm group type: Experimental
description: Oral rucaparib and Intravenous (IV) nivolumab (combination therapy)
Cohort A1
Cohort A2
intervention type: Drug
intervention name: Rucaparib
description: Oral rucaparib will be administered twice daily
arm group label: Cohort A: Ovarian Cancer Cohort
other name: Rubraca
other name: CO-338
intervention type: Drug
intervention name: Nivolumab
description: IV nivolumab will be administered once every 4 weeks
arm group label: Cohort A: Ovarian Cancer Cohort
other name: Opdivo
other name: BMS-936558
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Kathleen N Moore, MD
role: Principal Investigator
affiliation: Lead Investigator for Ovarian Cohort A
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Fallopian Tube Neoplasms
mesh term: Carcinoma, Ovarian Epithelial
mesh term: Carcinoma, Endometrioid
mesh term: Cystadenocarcinoma, Serous
mesh term: Nivolumab
mesh term: Rucaparib
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The Sponsor made a business decision to discontinue the study due to low accrual.
point of contact: 