<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/NCT03029598</url>
  </required_header>
  <id_info>
    <org_study_id>9740</org_study_id>
    <secondary_id>NCI-2016-01962</secondary_id>
    <secondary_id>9740</secondary_id>
    <secondary_id>P30CA015704</secondary_id>
    <secondary_id>RG1716074</secondary_id>
    <nct_id>NCT03029598</nct_id>
  </id_info>
  <brief_title>Pembrolizumab and Carboplatin in Treating Patients With Relapsed or Refractory Ovarian, Fallopian Tube, or Primary Peritoneal Cancer</brief_title>
  <official_title>Anti-PD-1 Therapy in Combination With Platinum Chemotherapy for Platinum Resistant Ovarian, Fallopian Tube, and Primary Peritoneal Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Washington</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Washington</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase I/II trial studies how well pembrolizumab and carboplatin work in treating&#xD;
      patients with ovarian, fallopian tube, or primary peritoneal cancer that has come back&#xD;
      (relapsed) or has not responded to previous treatment (refractory). Immunotherapy with&#xD;
      monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the&#xD;
      cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in&#xD;
      chemotherapy, such as carboplatin, work in different ways to stop the growth of tumor cells,&#xD;
      either by killing the cells, by stopping them from dividing, or by stopping them from&#xD;
      spreading. Giving pembrolizumab and carboplatin with platinum resistant chemotherapy may work&#xD;
      better than platinum chemotherapy alone in treating patients with ovarian, fallopian tube, or&#xD;
      primary peritoneal cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To determine the clinical response rate of platinum chemotherapy and pembrolizumab&#xD;
      (MK-3475) in platinum chemotherapy pretreated ovarian, fallopian tube, and primary&#xD;
      peritoneal.&#xD;
&#xD;
      II. To examine whether retreatment with platinum chemotherapy in platinum resistant ovarian,&#xD;
      fallopian tube, and primary peritoneal cancers improves progression free survival by&#xD;
      concurrent administration of MK-3475.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To assess the safety and tolerability of concurrent administration of MK-3475 with&#xD;
      platinum chemotherapy in patients with platinum resistant recurrent ovarian, fallopian tube,&#xD;
      and primary peritoneal cancers.&#xD;
&#xD;
      II. To determine the relationship between PD-L1 expression and response to the combination of&#xD;
      MK-3475 and platinum.&#xD;
&#xD;
      III. To assess the overall survival of patients treated with the combination of MK-3475 and&#xD;
      platinum.&#xD;
&#xD;
      EXPLORATORY OBJECTIVE:&#xD;
&#xD;
      I. To explore whether treatment with MK-3475 and platinum alters soluble factors in sera,&#xD;
      peripheral immune responses and immune cell profile.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and carboplatin IV&#xD;
      over 30 minutes on days 8 and 15. Cycles repeat every 21 days for up to 24 months in the&#xD;
      absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up at 30 days, every 3 months for&#xD;
      1 year, every 6 months for 1 year, and then every 12 weeks thereafter.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 14, 2017</start_date>
  <completion_date type="Actual">December 31, 2021</completion_date>
  <primary_completion_date type="Actual">April 20, 2021</primary_completion_date>
  <phase>Phase 1/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>Response Rate (RR) Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1</measure>
    <time_frame>6 months</time_frame>
    <description>Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI/CT scans: 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>
  <primary_outcome>
    <measure>Progression-free Survival (PFS) Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1</measure>
    <time_frame>6 months</time_frame>
    <description>Analyzed using the Kaplan-Meier method. Kaplan-Meier estimates of the survival function with 95% confidence intervals (CIs) at specific time points (using Greenwood's formula for the standard error) were computed. Comparisons with the historical control PFS will be conducted by examining whether the 95% confidence internal covers the historical control proportions.&#xD;
Progression-free survival (PFS) is defined as the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse. Participants are evaluated by RECIST1.1 to determine if/when a participant's disease has progressed defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Count of Adverse Events Evaluated by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.</measure>
    <time_frame>Up to 3.5 years</time_frame>
    <description>The safety evaluation of the population included all patients who received at least one dose of study medication. The descriptions and grading scales found in the revised NCI CTCAE version 4.0 will be utilized for adverse event reporting where Grade refers to the severity of the AE.&#xD;
The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline:&#xD;
Grade 1 Mild; asymptomatic or mild symptoms Grade 2 Moderate; minimal Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care of activity of daily living Grade 4 Life-threatening consequences; urgent intervention indicated Grade 5 Death related to AE</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants That Were PD-L1 Positive Based On PD-L1 Expression of Primary Tumor Blocks Assessed by Immunohistochemical Staining</measure>
    <time_frame>Up to 3.5 years</time_frame>
    <description>PD-L1 antibody-stained archival tumor was evaluated by a board-certified pathologist and given a modified proportion score (MPS), or the overall percent of positive cells expressing PD-L1, and a MPS ≥ 5% was defined as PD-L1 positive.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>Up to 3.5 years</time_frame>
    <description>Analyzed using the Kaplan-Meier method. Kaplan-Meier estimates of the survival function with 95% CIs at specific time points (using Greenwood's formula for the standard error) were computed. Comparisons with the historical control OS will be conducted by examining whether the 95% confidence internal covers the historical control proportions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Best Overall Response (BOR)</measure>
    <time_frame>Up to 3.5 years</time_frame>
    <description>Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI/CT scans: 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>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival (PFS) Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1</measure>
    <time_frame>Up to 3.5 years</time_frame>
    <description>Analyzed using the Kaplan-Meier method. Kaplan-Meier estimates of the survival function with 95% CIs at specific time points (using Greenwood's formula for the standard error) were computed. Comparisons with the historical control PFS will be conducted by examining whether the 95% confidence internal covers the historical control proportions.&#xD;
Progression-free survival (PFS) is defined as the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse. Participants are evaluated by RECIST1.1 to determine if/when a participant's disease has progressed defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immune-related Best Overall Response (BOR) Assessed Using irRECIST (Immune-related Response Evaluation Criteria In Solid Tumors) Derived From Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1</measure>
    <time_frame>Up to 3.5 years</time_frame>
    <description>Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI/CT scans: 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>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immune-related Progression-free Survival (PFS) Using irRECIST (Immune-related Response Evaluation Criteria In Solid Tumors) Derived From Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1</measure>
    <time_frame>Up to 3.5 years</time_frame>
    <description>Progression-free survival (PFS) is defined as the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse. Participants are evaluated by RECIST1.1 to determine if/when a participant's disease has progressed defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">29</enrollment>
  <condition>Recurrent Fallopian Tube Carcinoma</condition>
  <condition>Recurrent Ovarian Carcinoma</condition>
  <condition>Recurrent Primary Peritoneal Carcinoma</condition>
  <arm_group>
    <arm_group_label>Treatment (pembrolizumab, carboplatin)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive pembrolizumab IV over 30 minutes on day 1 and carboplatin IV over 30 minutes on days 8 and 15. Cycles repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carboplatin</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (pembrolizumab, carboplatin)</arm_group_label>
    <other_name>Blastocarb</other_name>
    <other_name>Carboplat</other_name>
    <other_name>Carboplatin Hexal</other_name>
    <other_name>Carboplatino</other_name>
    <other_name>Carbosin</other_name>
    <other_name>Carbosol</other_name>
    <other_name>Carbotec</other_name>
    <other_name>CBDCA</other_name>
    <other_name>Displata</other_name>
    <other_name>Ercar</other_name>
    <other_name>JM-8</other_name>
    <other_name>Nealorin</other_name>
    <other_name>Novoplatinum</other_name>
    <other_name>Paraplatin</other_name>
    <other_name>Paraplatin AQ</other_name>
    <other_name>Paraplatine</other_name>
    <other_name>Platinwas</other_name>
    <other_name>Ribocarbo</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (pembrolizumab, carboplatin)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (pembrolizumab, carboplatin)</arm_group_label>
    <other_name>Keytruda</other_name>
    <other_name>Lambrolizumab</other_name>
    <other_name>MK-3475</other_name>
    <other_name>SCH 900475</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Have a diagnosis of ovarian, fallopian tube, or primary peritoneal cancer patients who&#xD;
             had a complete response to primary treatment with platinum based chemotherapy, have&#xD;
             progressed within 6 months of completing platinum based chemotherapy and have&#xD;
             subsequently received at least one, non-platinum-based, therapy&#xD;
&#xD;
          -  Have relapsed, refractory, or progressive disease following last line of treatment&#xD;
&#xD;
          -  Have estimated life expectancy of at least 3 months&#xD;
&#xD;
          -  Be willing and able to provide written informed consent/assent for the trial&#xD;
&#xD;
          -  Have measurable disease with at least 1 unidimensional lesion based on Response&#xD;
             Evaluation Criteria in Solid Tumors (RECIST) 1.1&#xD;
&#xD;
          -  Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)&#xD;
             performance scale&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt;= 1,500/mcL (within 10 days of treatment initiation)&#xD;
&#xD;
          -  Platelets &gt;= 100,000/mcL (within 10 days of treatment initiation)&#xD;
&#xD;
          -  Hemoglobin &gt;= 9 g/dL or &gt;= 5.6 mmol/L without transfusion or erythropoietin (EPO)&#xD;
             dependency (within 7 days of assessment) (within 10 days of treatment initiation)&#xD;
&#xD;
          -  Serum creatinine =&lt; 1.5 X upper limit of normal (ULN) OR measured or calculated&#xD;
             creatinine clearance (glomerular filtration rate [GFR] can also be used in place of&#xD;
             creatinine or creatinine clearance [CrCl]) &gt;= 60 mL/min for subject with creatinine&#xD;
             levels &gt; 1.5 X institutional ULN (within 10 days of treatment initiation)&#xD;
&#xD;
             *Creatinine clearance should be calculated per institutional standard&#xD;
&#xD;
          -  Serum total bilirubin =&lt; 1.5 X ULN OR direct bilirubin =&lt; ULN for subjects with total&#xD;
             bilirubin levels &gt; 1.5 ULN (within 10 days of treatment initiation)&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and&#xD;
             alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =&lt; 2.5 X&#xD;
             ULN OR =&lt; 5 X ULN for subjects with liver metastases (within 10 days of treatment&#xD;
             initiation)&#xD;
&#xD;
          -  Albumin &gt;= 2.5 mg/dL (within 10 days of treatment initiation)&#xD;
&#xD;
          -  International normalized ratio (INR) or prothrombin time (PT) =&lt; 1.5 X ULN unless&#xD;
             subject is receiving anticoagulant therapy as long as PT or partial thromboplastin&#xD;
             time (PTT) is within therapeutic range of intended use of anticoagulants (within 10&#xD;
             days of treatment initiation)&#xD;
&#xD;
          -  Activated partial thromboplastin time (aPTT) =&lt; 1.5 X ULN unless subject is receiving&#xD;
             anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use&#xD;
             of anticoagulants (within 10 days of treatment initiation)&#xD;
&#xD;
          -  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;
          -  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;
        Exclusion Criteria:&#xD;
&#xD;
          -  Is currently participating and receiving study therapy or has participated in a study&#xD;
             of an investigational agent and received study therapy within 4 weeks of the first&#xD;
             dose of treatment&#xD;
&#xD;
          -  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;
             * Short-term administration of systemic steroids (i.e., for allergic reactions or the&#xD;
             management of immune related adverse events [irAEs]) is allowed&#xD;
&#xD;
          -  Has a known history of active TB (Bacillus tuberculosis)&#xD;
&#xD;
          -  Hypersensitivity to pembrolizumab or any of its excipients&#xD;
&#xD;
          -  Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study&#xD;
             day 1 or who has not recovered (i.e., =&lt; grade 1 or at baseline) from adverse events&#xD;
             due to agents administered more than 4 weeks earlier&#xD;
&#xD;
          -  Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy&#xD;
             within 2 weeks prior to study day 1 or who has not recovered (i.e., =&lt; grade 1 or at&#xD;
             baseline) from adverse events due to a previously administered agent&#xD;
&#xD;
               -  Note: subjects with =&lt; grade 2 neuropathy are an exception to this criterion and&#xD;
                  may qualify for the study&#xD;
&#xD;
               -  Note: if subject received major surgery, they must have recovered adequately from&#xD;
                  the toxicity and/or complications from the intervention prior to starting therapy&#xD;
&#xD;
          -  Has a known additional malignancy that is progressing or requires active treatment;&#xD;
             exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the&#xD;
             skin that has undergone potentially curative therapy or in situ cervical cancer&#xD;
&#xD;
          -  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; this exception does not include&#xD;
             carcinomatous meningitis which is excluded regardless of clinical stability&#xD;
&#xD;
          -  Has active autoimmune disease that has required systemic treatment in the past 2 years&#xD;
             (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive&#xD;
             drugs); replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid&#xD;
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a&#xD;
             form of systemic treatment&#xD;
&#xD;
          -  Has a history of (non-infectious) pneumonitis that required steroids or current&#xD;
             pneumonitis&#xD;
&#xD;
          -  Has an active infection requiring systemic therapy&#xD;
&#xD;
          -  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;
          -  Has known psychiatric or substance abuse disorders that would interfere with&#xD;
             cooperation with the requirements of the trial&#xD;
&#xD;
          -  Is pregnant or breastfeeding, or expecting to conceive children within the projected&#xD;
             duration of the trial, starting with the pre-screening or screening visit through 120&#xD;
             days after the last dose of trial treatment&#xD;
&#xD;
          -  Clinically significant cardiovascular disease&#xD;
&#xD;
          -  Known severe hypersensitivity reactions to monoclonal antibodies or carboplatin &gt;=&#xD;
             grade 3, any history of anaphylaxis, or uncontrolled asthma&#xD;
&#xD;
          -  Has received prior therapy with pembrolizumab&#xD;
&#xD;
          -  Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)&#xD;
&#xD;
          -  Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or&#xD;
             hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is&#xD;
             detected)&#xD;
&#xD;
          -  Has received a live vaccine within 30 days of planned start of study therapy&#xD;
&#xD;
               -  Note: seasonal influenza vaccines for injection are generally inactivated flu&#xD;
                  vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist)&#xD;
                  are live attenuated vaccines, and are not 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>John Liao</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fred Hutch/University of Washington Cancer Consortium</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Fred Hutch/University of Washington Cancer Consortium</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>January 20, 2017</study_first_submitted>
  <study_first_submitted_qc>January 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 24, 2017</study_first_posted>
  <results_first_submitted>April 20, 2022</results_first_submitted>
  <results_first_submitted_qc>July 22, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">July 26, 2022</results_first_posted>
  <last_update_submitted>July 22, 2022</last_update_submitted>
  <last_update_submitted_qc>July 22, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 26, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Washington</investigator_affiliation>
    <investigator_full_name>John Liao</investigator_full_name>
    <investigator_title>Associate Professor, Division of Gynecologic Oncology</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carboplatin</mesh_term>
    <mesh_term>Pembrolizumab</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 7, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/98/NCT03029598/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>August 20, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/98/NCT03029598/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Treatment (Pembrolizumab, Carboplatin)</title>
          <description>Patients receive pembrolizumab IV over 30 minutes on day 1 and carboplatin IV over 30 minutes on days 8 and 15. Cycles repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity.&#xD;
Carboplatin: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Pembrolizumab: Given IV</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="29"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="29"/>
              </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>Treatment (Pembrolizumab, Carboplatin)</title>
          <description>Patients receive pembrolizumab IV over 30 minutes on day 1 and carboplatin IV over 30 minutes on days 8 and 15. Cycles repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity.&#xD;
Carboplatin: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Pembrolizumab: Given IV</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="29"/>
          </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="65" lower_limit="41" upper_limit="80"/>
                  </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="29"/>
                  </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="29"/>
                  </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="1"/>
                  </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="28"/>
                  </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>
          <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="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Canada</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Response Rate (RR) Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1</title>
        <description>Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI/CT scans: 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>6 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Pembrolizumab, Carboplatin)</title>
            <description>Patients receive pembrolizumab IV over 30 minutes on day 1 and carboplatin IV over 30 minutes on days 8 and 15. Cycles repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity.&#xD;
Carboplatin: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Pembrolizumab: Given IV</description>
          </group>
        </group_list>
        <measure>
          <title>Response Rate (RR) Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1</title>
          <description>Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI/CT scans: 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>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Patients that achieved a Partial Response (PR)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Patient achieved Stable Disease (SD)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Patients that had Progressive Disease (PD)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Progression-free Survival (PFS) Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1</title>
        <description>Analyzed using the Kaplan-Meier method. Kaplan-Meier estimates of the survival function with 95% confidence intervals (CIs) at specific time points (using Greenwood's formula for the standard error) were computed. Comparisons with the historical control PFS will be conducted by examining whether the 95% confidence internal covers the historical control proportions.&#xD;
Progression-free survival (PFS) is defined as the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse. Participants are evaluated by RECIST1.1 to determine if/when a participant's disease has progressed defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.</description>
        <time_frame>6 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Pembrolizumab, Carboplatin)</title>
            <description>Patients receive pembrolizumab IV over 30 minutes on day 1 and carboplatin IV over 30 minutes on days 8 and 15. Cycles repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity.&#xD;
Carboplatin: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Pembrolizumab: Given IV</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-free Survival (PFS) Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1</title>
          <description>Analyzed using the Kaplan-Meier method. Kaplan-Meier estimates of the survival function with 95% confidence intervals (CIs) at specific time points (using Greenwood's formula for the standard error) were computed. Comparisons with the historical control PFS will be conducted by examining whether the 95% confidence internal covers the historical control proportions.&#xD;
Progression-free survival (PFS) is defined as the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse. Participants are evaluated by RECIST1.1 to determine if/when a participant's disease has progressed defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.</description>
          <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="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.63" lower_limit="4.30" upper_limit="4.97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Count of Adverse Events Evaluated by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.</title>
        <description>The safety evaluation of the population included all patients who received at least one dose of study medication. The descriptions and grading scales found in the revised NCI CTCAE version 4.0 will be utilized for adverse event reporting where Grade refers to the severity of the AE.&#xD;
The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline:&#xD;
Grade 1 Mild; asymptomatic or mild symptoms Grade 2 Moderate; minimal Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care of activity of daily living Grade 4 Life-threatening consequences; urgent intervention indicated Grade 5 Death related to AE</description>
        <time_frame>Up to 3.5 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Pembrolizumab, Carboplatin)</title>
            <description>Patients receive pembrolizumab IV over 30 minutes on day 1 and carboplatin IV over 30 minutes on days 8 and 15. Cycles repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity.&#xD;
Carboplatin: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Pembrolizumab: Given IV</description>
          </group>
        </group_list>
        <measure>
          <title>Count of Adverse Events Evaluated by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.</title>
          <description>The safety evaluation of the population included all patients who received at least one dose of study medication. The descriptions and grading scales found in the revised NCI CTCAE version 4.0 will be utilized for adverse event reporting where Grade refers to the severity of the AE.&#xD;
The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline:&#xD;
Grade 1 Mild; asymptomatic or mild symptoms Grade 2 Moderate; minimal Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care of activity of daily living Grade 4 Life-threatening consequences; urgent intervention indicated Grade 5 Death related to AE</description>
          <units>adverse events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Grade 1 - Total Number of Reported AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="597"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 2 - Total Number of Reported AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="169"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 3 - Total Number of Reported AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 4 - Total Number of Reported AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants That Were PD-L1 Positive Based On PD-L1 Expression of Primary Tumor Blocks Assessed by Immunohistochemical Staining</title>
        <description>PD-L1 antibody-stained archival tumor was evaluated by a board-certified pathologist and given a modified proportion score (MPS), or the overall percent of positive cells expressing PD-L1, and a MPS ≥ 5% was defined as PD-L1 positive.</description>
        <time_frame>Up to 3.5 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Pembrolizumab, Carboplatin)</title>
            <description>Patients receive pembrolizumab IV over 30 minutes on day 1 and carboplatin IV over 30 minutes on days 8 and 15. Cycles repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity.&#xD;
Carboplatin: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Pembrolizumab: Given IV</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants That Were PD-L1 Positive Based On PD-L1 Expression of Primary Tumor Blocks Assessed by Immunohistochemical Staining</title>
          <description>PD-L1 antibody-stained archival tumor was evaluated by a board-certified pathologist and given a modified proportion score (MPS), or the overall percent of positive cells expressing PD-L1, and a MPS ≥ 5% was defined as PD-L1 positive.</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="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival (OS)</title>
        <description>Analyzed using the Kaplan-Meier method. Kaplan-Meier estimates of the survival function with 95% CIs at specific time points (using Greenwood's formula for the standard error) were computed. Comparisons with the historical control OS will be conducted by examining whether the 95% confidence internal covers the historical control proportions.</description>
        <time_frame>Up to 3.5 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Pembrolizumab, Carboplatin)</title>
            <description>Patients receive pembrolizumab IV over 30 minutes on day 1 and carboplatin IV over 30 minutes on days 8 and 15. Cycles repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity.&#xD;
Carboplatin: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Pembrolizumab: Given IV</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS)</title>
          <description>Analyzed using the Kaplan-Meier method. Kaplan-Meier estimates of the survival function with 95% CIs at specific time points (using Greenwood's formula for the standard error) were computed. Comparisons with the historical control OS will be conducted by examining whether the 95% confidence internal covers the historical control proportions.</description>
          <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="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.3" lower_limit="6.094" upper_limit="16.506"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Best Overall Response (BOR)</title>
        <description>Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI/CT scans: 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 3.5 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Pembrolizumab, Carboplatin)</title>
            <description>Patients receive pembrolizumab IV over 30 minutes on day 1 and carboplatin IV over 30 minutes on days 8 and 15. Cycles repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity.&#xD;
Carboplatin: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Pembrolizumab: Given IV</description>
          </group>
        </group_list>
        <measure>
          <title>Best Overall Response (BOR)</title>
          <description>Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI/CT scans: 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>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Partial Response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Stable Disease</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Progressive Disease</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression-free Survival (PFS) Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1</title>
        <description>Analyzed using the Kaplan-Meier method. Kaplan-Meier estimates of the survival function with 95% CIs at specific time points (using Greenwood's formula for the standard error) were computed. Comparisons with the historical control PFS will be conducted by examining whether the 95% confidence internal covers the historical control proportions.&#xD;
Progression-free survival (PFS) is defined as the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse. Participants are evaluated by RECIST1.1 to determine if/when a participant's disease has progressed defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.</description>
        <time_frame>Up to 3.5 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Pembrolizumab, Carboplatin)</title>
            <description>Patients receive pembrolizumab IV over 30 minutes on day 1 and carboplatin IV over 30 minutes on days 8 and 15. Cycles repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity.&#xD;
Carboplatin: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Pembrolizumab: Given IV</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-free Survival (PFS) Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1</title>
          <description>Analyzed using the Kaplan-Meier method. Kaplan-Meier estimates of the survival function with 95% CIs at specific time points (using Greenwood's formula for the standard error) were computed. Comparisons with the historical control PFS will be conducted by examining whether the 95% confidence internal covers the historical control proportions.&#xD;
Progression-free survival (PFS) is defined as the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse. Participants are evaluated by RECIST1.1 to determine if/when a participant's disease has progressed defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.</description>
          <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="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.63" lower_limit="4.3" upper_limit="4.97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Immune-related Best Overall Response (BOR) Assessed Using irRECIST (Immune-related Response Evaluation Criteria In Solid Tumors) Derived From Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1</title>
        <description>Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI/CT scans: 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 3.5 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Pembrolizumab, Carboplatin)</title>
            <description>Patients receive pembrolizumab IV over 30 minutes on day 1 and carboplatin IV over 30 minutes on days 8 and 15. Cycles repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity.&#xD;
Carboplatin: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Pembrolizumab: Given IV</description>
          </group>
        </group_list>
        <measure>
          <title>Immune-related Best Overall Response (BOR) Assessed Using irRECIST (Immune-related Response Evaluation Criteria In Solid Tumors) Derived From Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1</title>
          <description>Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI/CT scans: 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>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Partial Response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Stable Disease</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Progressive Disease</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Immune-related Progression-free Survival (PFS) Using irRECIST (Immune-related Response Evaluation Criteria In Solid Tumors) Derived From Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1</title>
        <description>Progression-free survival (PFS) is defined as the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse. Participants are evaluated by RECIST1.1 to determine if/when a participant's disease has progressed defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.</description>
        <time_frame>Up to 3.5 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Pembrolizumab, Carboplatin)</title>
            <description>Patients receive pembrolizumab IV over 30 minutes on day 1 and carboplatin IV over 30 minutes on days 8 and 15. Cycles repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity.&#xD;
Carboplatin: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Pembrolizumab: Given IV</description>
          </group>
        </group_list>
        <measure>
          <title>Immune-related Progression-free Survival (PFS) Using irRECIST (Immune-related Response Evaluation Criteria In Solid Tumors) Derived From Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1</title>
          <description>Progression-free survival (PFS) is defined as the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse. Participants are evaluated by RECIST1.1 to determine if/when a participant's disease has progressed defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.</description>
          <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="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.63" lower_limit="4.30" upper_limit="4.97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>The safety population included all patients who received at least one dose of study medication. Anyone that received at least 1 treatment dose will be evaluated. After the end of treatment, each subject will be followed for 30 days or prior to initiation of new treatment for adverse event monitoring (serious adverse events will be collected for 90 days after the end of treatment. The complete adverse event evaluation period for all treated participants is 3.5 years.</time_frame>
      <desc>We used CTCAE v4.0 for this study. The adverse events reported here include all events regardless of whether they were unrelated and related to study treatment). Please note we recorded every adverse event for every subject regardless of severity. For example, a subject may have an injection site reaction at the site of treatment administration; each each time an injection site reactions is reported, during the study, it is recorded for that subject.</desc>
      <group_list>
        <group group_id="E1">
          <title>Treatment (Pembrolizumab, Carboplatin)</title>
          <description>Patients receive pembrolizumab IV over 30 minutes on day 1 and carboplatin IV over 30 minutes on days 8 and 15. Cycles repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity.&#xD;
Carboplatin: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Pembrolizumab: Given IV</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-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="28" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Disease progression leading to hospice</sub_title>
                <description>For this study disease progression was not defined as an SAE, unless it led to hospitalization or death</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>3</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="25" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <description>31 reported adverse events were deemed unrelated to study treatment</description>
                <counts group_id="E1" events="82" subjects_affected="25" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <description>5 reported adverse events were deemed unrelated to study treatment</description>
                <counts group_id="E1" events="26" subjects_affected="13" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Lymphopenia</sub_title>
                <description>3 reported adverse events were deemed unrelated to study treatment</description>
                <counts group_id="E1" events="100" subjects_affected="19" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <description>4 reported adverse events were deemed unrelated to study treatment</description>
                <counts group_id="E1" events="37" subjects_affected="13" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <description>2 reported adverse events were deemed unrelated to study treatment</description>
                <counts group_id="E1" events="35" subjects_affected="14" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" events="25" subjects_affected="7" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <description>18 reported adverse events were deemed unrelated to study treatment</description>
                <counts group_id="E1" events="42" subjects_affected="14" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <description>24 reported adverse events were deemed unrelated to study treatment</description>
                <counts group_id="E1" events="31" subjects_affected="14" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <description>23 reported adverse events were deemed unrelated to study treatment</description>
                <counts group_id="E1" events="27" subjects_affected="14" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Hypomagnesemia</sub_title>
                <description>6 reported adverse events were deemed unrelated to study treatment</description>
                <counts group_id="E1" events="24" subjects_affected="14" subjects_at_risk="29"/>
              </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>Director of Clinical Operations</name_or_title>
      <organization>University of Washington - Cancer Vaccine Institute</organization>
      <phone>2062459258</phone>
      <email>childj@uw.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/NCT03029598
org study id: 9740
secondary id: NCI-2016-01962
secondary id: 9740
secondary id: P30CA015704
secondary id: RG1716074
nct id: NCT03029598
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This phase I/II trial studies how well pembrolizumab and carboplatin work in treating
      patients with ovarian, fallopian tube, or primary peritoneal cancer that has come back
      (relapsed) or has not responded to previous treatment (refractory). Immunotherapy with
      monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the
      cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in
      chemotherapy, such as carboplatin, work in different ways to stop the growth of tumor cells,
      either by killing the cells, by stopping them from dividing, or by stopping them from
      spreading. Giving pembrolizumab and carboplatin with platinum resistant chemotherapy may work
      better than platinum chemotherapy alone in treating patients with ovarian, fallopian tube, or
      primary peritoneal cancer.
PRIMARY OBJECTIVES:

      I. To determine the clinical response rate of platinum chemotherapy and pembrolizumab
      (MK-3475) in platinum chemotherapy pretreated ovarian, fallopian tube, and primary
      peritoneal.

      II. To examine whether retreatment with platinum chemotherapy in platinum resistant ovarian,
      fallopian tube, and primary peritoneal cancers improves progression free survival by
      concurrent administration of MK-3475.

      SECONDARY OBJECTIVES:

      I. To assess the safety and tolerability of concurrent administration of MK-3475 with
      platinum chemotherapy in patients with platinum resistant recurrent ovarian, fallopian tube,
      and primary peritoneal cancers.

      II. To determine the relationship between PD-L1 expression and response to the combination of
      MK-3475 and platinum.

      III. To assess the overall survival of patients treated with the combination of MK-3475 and
      platinum.

      EXPLORATORY OBJECTIVE:

      I. To explore whether treatment with MK-3475 and platinum alters soluble factors in sera,
      peripheral immune responses and immune cell profile.

      OUTLINE:

      Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and carboplatin IV
      over 30 minutes on days 8 and 15. Cycles repeat every 21 days for up to 24 months in the
      absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 30 days, every 3 months for
      1 year, every 6 months for 1 year, and then every 12 weeks thereafter.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Response Rate (RR) Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
time frame: 6 months
description: Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI/CT scans: 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) Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
time frame: 6 months
description: Analyzed using the Kaplan-Meier method. Kaplan-Meier estimates of the survival function with 95% confidence intervals (CIs) at specific time points (using Greenwood's formula for the standard error) were computed. Comparisons with the historical control PFS will be conducted by examining whether the 95% confidence internal covers the historical control proportions.
Progression-free survival (PFS) is defined as the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse. Participants are evaluated by RECIST1.1 to determine if/when a participant's disease has progressed defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
measure: Count of Adverse Events Evaluated by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.
time frame: Up to 3.5 years
description: The safety evaluation of the population included all patients who received at least one dose of study medication. The descriptions and grading scales found in the revised NCI CTCAE version 4.0 will be utilized for adverse event reporting where Grade refers to the severity of the AE.
The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline:
Grade 1 Mild; asymptomatic or mild symptoms Grade 2 Moderate; minimal Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care of activity of daily living Grade 4 Life-threatening consequences; urgent intervention indicated Grade 5 Death related to AE
measure: Number of Participants That Were PD-L1 Positive Based On PD-L1 Expression of Primary Tumor Blocks Assessed by Immunohistochemical Staining
time frame: Up to 3.5 years
description: PD-L1 antibody-stained archival tumor was evaluated by a board-certified pathologist and given a modified proportion score (MPS), or the overall percent of positive cells expressing PD-L1, and a MPS ≥ 5% was defined as PD-L1 positive.
measure: Overall Survival (OS)
time frame: Up to 3.5 years
description: Analyzed using the Kaplan-Meier method. Kaplan-Meier estimates of the survival function with 95% CIs at specific time points (using Greenwood's formula for the standard error) were computed. Comparisons with the historical control OS will be conducted by examining whether the 95% confidence internal covers the historical control proportions.
measure: Best Overall Response (BOR)
time frame: Up to 3.5 years
description: Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI/CT scans: 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) Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
time frame: Up to 3.5 years
description: Analyzed using the Kaplan-Meier method. Kaplan-Meier estimates of the survival function with 95% CIs at specific time points (using Greenwood's formula for the standard error) were computed. Comparisons with the historical control PFS will be conducted by examining whether the 95% confidence internal covers the historical control proportions.
Progression-free survival (PFS) is defined as the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse. Participants are evaluated by RECIST1.1 to determine if/when a participant's disease has progressed defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
measure: Immune-related Best Overall Response (BOR) Assessed Using irRECIST (Immune-related Response Evaluation Criteria In Solid Tumors) Derived From Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
time frame: Up to 3.5 years
description: Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI/CT scans: 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: Immune-related Progression-free Survival (PFS) Using irRECIST (Immune-related Response Evaluation Criteria In Solid Tumors) Derived From Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
time frame: Up to 3.5 years
description: Progression-free survival (PFS) is defined as the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse. Participants are evaluated by RECIST1.1 to determine if/when a participant's disease has progressed defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
arm group label: Treatment (pembrolizumab, carboplatin)
arm group type: Experimental
description: Patients receive pembrolizumab IV over 30 minutes on day 1 and carboplatin IV over 30 minutes on days 8 and 15. Cycles repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: Carboplatin
description: Given IV
arm group label: Treatment (pembrolizumab, carboplatin)
other name: Blastocarb
other name: Carboplat
other name: Carboplatin Hexal
other name: Carboplatino
other name: Carbosin
other name: Carbosol
other name: Carbotec
other name: CBDCA
other name: Displata
other name: Ercar
other name: JM-8
other name: Nealorin
other name: Novoplatinum
other name: Paraplatin
other name: Paraplatin AQ
other name: Paraplatine
other name: Platinwas
other name: Ribocarbo
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Treatment (pembrolizumab, carboplatin)
intervention type: Biological
intervention name: Pembrolizumab
description: Given IV
arm group label: Treatment (pembrolizumab, carboplatin)
other name: Keytruda
other name: Lambrolizumab
other name: MK-3475
other name: SCH 900475
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: John Liao
role: Principal Investigator
affiliation: Fred Hutch/University of Washington Cancer Consortium
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Washington
investigator full name: John Liao
investigator title: Associate Professor, Division of Gynecologic Oncology
mesh term: Carcinoma
mesh term: Recurrence
mesh term: Carboplatin
mesh term: Pembrolizumab
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 