<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/NCT03274661</url>
  </required_header>
  <id_info>
    <org_study_id>MK-3475-663</org_study_id>
    <nct_id>NCT03274661</nct_id>
  </id_info>
  <brief_title>Pembrolizumab Activity in Patients With Homologous Recombination Competent and Deficient Tumors</brief_title>
  <official_title>Evaluating Immune Checkpoint Inhibition In Solid Tumor Patients With Homologous Recombination Repair Deficiency</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Baptist Health South Florida</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Miami Cancer Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Baptist Health South Florida</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>
      Phase II trial in which patients with metastatic solid tumors experiencing progression after&#xD;
      first line standard chemotherapy or for which there is no standard chemotherapy, and for&#xD;
      which pembrolizumab does not have an FDA or compendia listing approved indication, will&#xD;
      receive pembrolizumab intravenously at a dose of 200 mg every 3 weeks.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients with metastatic or recurrent solid malignancy who have progressed on first line&#xD;
      standard of care treatment or for which defined standard of care does not exist or is not&#xD;
      readily available are eligible to participate on this trial. Patients for which pembrolizumab&#xD;
      has an FDA approved indication and for whom pembrolizumab is covered by their insurance&#xD;
      should receive standard commercial pembrolizumab and will not be eligible for this trial.&#xD;
&#xD;
      The primary objective of this trial is to evaluate the Immune-Related Objective Response Rate&#xD;
      (IR-ORR) achieved with pembrolizumab in patients with Fanconi Anemia Repair Pathway&#xD;
      functionally competent and functionally deficient tumors.&#xD;
&#xD;
      Trial treatment should be administered on Day 1 of each cycle after all&#xD;
      procedures/assessments have been completed. Trial treatment may be administered up to 3 days&#xD;
      before or after the scheduled Day 1 of each cycle due to administrative reasons.&#xD;
&#xD;
      All trial treatments will be administered on an outpatient basis.&#xD;
&#xD;
      Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks. Target&#xD;
      infusion timing is 30 minutes.&#xD;
&#xD;
      Expansion Cohort:&#xD;
&#xD;
      Ten (10) additional subjects with the diagnosis of metastatic or recurrent endometrial&#xD;
      carcinoma will be enrolled in the trial at the conclusion of regular enrollment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">November 3, 2017</start_date>
  <completion_date type="Anticipated">October 15, 2026</completion_date>
  <primary_completion_date type="Anticipated">March 15, 2025</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Eligible participants will receive pembrolizumab intravenously at a dose of 200 mg every 3 weeks.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>immune-related objective response rate</measure>
    <time_frame>every 2 cycles (3 weeks cycles); that is before every third dose of pembrolizumab</time_frame>
    <description>Immune-related Response Criteria (irRC) will be utilized for assessment of response to therapy.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>20-week immune-related progression-free survival rate</measure>
    <time_frame>20-week</time_frame>
    <description>Immune-related Response Criteria (irRC) will be utilized for assessment of response to therapy.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Solid Tumor, Adult</condition>
  <arm_group>
    <arm_group_label>Pembrolizumab 200 mg Q3W</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pembrolizumab 200 mg Intravenous Infusion every 3 weeks administered on Day 1 of each 3 week cycle</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pembrolizumab 200 mg Q3W</intervention_name>
    <description>Pembrolizumab 200 mg Intravenous Infusion every 3 weeks administered on Day 1 of each 3 week cycle</description>
    <arm_group_label>Pembrolizumab 200 mg Q3W</arm_group_label>
    <other_name>Pembrolizumab 200 mg</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Have measurable disease based on RECIST 1.1.&#xD;
&#xD;
          -  Be willing to provide consent for retrieval of archival tumor material tissue from a&#xD;
             previously obtained core or excisional biopsy of a tumor lesion.&#xD;
&#xD;
          -  Have a tumor presentation at screening for which pembrolizumab does not have an FDA&#xD;
             approved indication for commercial use.&#xD;
&#xD;
          -  Have a performance status of 0, 1 or 2 on the ECOG Performance Scale.&#xD;
&#xD;
          -  Demonstrate adequate organ function&#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.&#xD;
&#xD;
        Expansion cohort - additional criteria&#xD;
&#xD;
          1. Diagnosis of Endometrial Carcinoma or Sarcoma which is metastatic and has failed&#xD;
             standard treatment or is recurrent, or for which standard chemotherapy is&#xD;
             contraindicated or refused by patient.&#xD;
&#xD;
          2. Sufficient tissue is available for correlative studies&#xD;
&#xD;
          3. MSI studies have been performed, either by immunohistochemistry or next generation&#xD;
             sequencing and results show that patient is MS low or stable.&#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, or used an investigational&#xD;
             device within 4 weeks of the first 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;
          -  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 a known history of active Bacillus Tuberculosis&#xD;
&#xD;
          -  Hypersensitivity to pembrolizumab or any of its excipients.&#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. This exception does not include carcinomatous meningitis which is&#xD;
             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).&#xD;
&#xD;
          -  Has immunohistochemically proven mismatch repair deficient cancer&#xD;
&#xD;
          -  Has a history of (non-infectious) pneumonitis that required steroids or current&#xD;
             pneumonitis&#xD;
&#xD;
          -  Evidence of interstitial lung disease.&#xD;
&#xD;
          -  Has an active infection requiring systemic therapy.&#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 or father children within the&#xD;
             projected duration of the trial, starting with the pre-screening or screening visit&#xD;
             through 120 days after the last dose of trial treatment.&#xD;
&#xD;
          -  Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.&#xD;
&#xD;
          -  Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).&#xD;
&#xD;
          -  Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA&#xD;
             [qualitative] is detected).&#xD;
&#xD;
          -  Has received a live vaccine within 30 days of planned start of study therapy. Note:&#xD;
             Seasonal influenza vaccines for injection are generally inactivated flu vaccines and&#xD;
             are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live&#xD;
             attenuated vaccines, and are not allowed.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>John P Diaz, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Miami Cancer Institute at Baptist Health, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Miami Cancer Institute at Baptist Health, Inc.</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33176</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://baptisthealth.net/cancer-care/home</url>
    <description>MCI - Website</description>
  </link>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>September 5, 2017</study_first_submitted>
  <study_first_submitted_qc>September 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 7, 2017</study_first_posted>
  <last_update_submitted>November 18, 2022</last_update_submitted>
  <last_update_submitted_qc>November 18, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 21, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>solid tumor, Pembrolizumab,</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pembrolizumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>August 22, 2023</submitted>
    <returned>September 12, 2023</returned>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03274661
org study id: MK-3475-663
nct id: NCT03274661
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Phase II trial in which patients with metastatic solid tumors experiencing progression after
      first line standard chemotherapy or for which there is no standard chemotherapy, and for
      which pembrolizumab does not have an FDA or compendia listing approved indication, will
      receive pembrolizumab intravenously at a dose of 200 mg every 3 weeks.
Patients with metastatic or recurrent solid malignancy who have progressed on first line
      standard of care treatment or for which defined standard of care does not exist or is not
      readily available are eligible to participate on this trial. Patients for which pembrolizumab
      has an FDA approved indication and for whom pembrolizumab is covered by their insurance
      should receive standard commercial pembrolizumab and will not be eligible for this trial.

      The primary objective of this trial is to evaluate the Immune-Related Objective Response Rate
      (IR-ORR) achieved with pembrolizumab in patients with Fanconi Anemia Repair Pathway
      functionally competent and functionally deficient tumors.

      Trial treatment should be administered on Day 1 of each cycle after all
      procedures/assessments have been completed. Trial treatment may be administered up to 3 days
      before or after the scheduled Day 1 of each cycle due to administrative reasons.

      All trial treatments will be administered on an outpatient basis.

      Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks. Target
      infusion timing is 30 minutes.

      Expansion Cohort:

      Ten (10) additional subjects with the diagnosis of metastatic or recurrent endometrial
      carcinoma will be enrolled in the trial at the conclusion of regular enrollment.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Eligible participants will receive pembrolizumab intravenously at a dose of 200 mg every 3 weeks.
primary purpose: Treatment
masking: None (Open Label)
measure: immune-related objective response rate
time frame: every 2 cycles (3 weeks cycles); that is before every third dose of pembrolizumab
description: Immune-related Response Criteria (irRC) will be utilized for assessment of response to therapy.
measure: 20-week immune-related progression-free survival rate
time frame: 20-week
description: Immune-related Response Criteria (irRC) will be utilized for assessment of response to therapy.
arm group label: Pembrolizumab 200 mg Q3W
arm group type: Experimental
description: Pembrolizumab 200 mg Intravenous Infusion every 3 weeks administered on Day 1 of each 3 week cycle
intervention type: Drug
intervention name: Pembrolizumab 200 mg Q3W
description: Pembrolizumab 200 mg Intravenous Infusion every 3 weeks administered on Day 1 of each 3 week cycle
arm group label: Pembrolizumab 200 mg Q3W
other name: Pembrolizumab 200 mg
criteria: 
gender: All
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: No
last name: John P Diaz, MD
role: Principal Investigator
affiliation: Miami Cancer Institute at Baptist Health, Inc.
facility: 
country: United States
url: http://baptisthealth.net/cancer-care/home
description: MCI - Website
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Pembrolizumab
sharing ipd: No
submitted: August 22, 2023
returned: September 12, 2023