<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/NCT04483544</url>
  </required_header>
  <id_info>
    <org_study_id>2019-JEK-DIA-001</org_study_id>
    <nct_id>NCT04483544</nct_id>
  </id_info>
  <brief_title>Pembrolizumab and Olaparib in Cervical Cancer Patients</brief_title>
  <official_title>Immunotherapy in Combination With PARP Inhibition in Advanced Cervical Cancer Patients Functionally Competent or Deficient for the Fanconi Anemia Repair Pathway</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Baptist Health South Florida</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Florida Department of Health</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</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>
      The study is a non-randomized, open-label phase II clinical trial to test the investigational&#xD;
      combination of the drug pembrolizumab with the drug olaparib in patients diagnosed with&#xD;
      advanced or recurrent cervical carcinoma after standard chemotherapy.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 3, 2020</start_date>
  <completion_date type="Anticipated">November 1, 2031</completion_date>
  <primary_completion_date type="Anticipated">November 1, 2030</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>PD-1 inhibitor pembrolizumab, in combination with the PARP inhibitor olaparib</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Immune overall response rate</measure>
    <time_frame>3 years</time_frame>
    <description>Overall objective Response Rate by Immune Response Evaluation Criteria in Solid Tumors (iRECIST) criteria (iORR)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival</measure>
    <time_frame>3 years</time_frame>
    <description>Defined among all treated patients as the time from first dose of study drug until the first date of either disease progression or death due to any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patient reporting treatment-emergent adverse events (TEAEs)</measure>
    <time_frame>3 years</time_frame>
    <description>The number of patients reporting treatment emergent adverse events (TEAEs) defined as an AE that occurs or worsens in the period extending from the first dose of study drug to 30 days after the last dose of study drug in this study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with baseline tumor deficiencies</measure>
    <time_frame>baseline</time_frame>
    <description>The number of patients with baseline tumor deficiencies in the Fanconi Anemia pathway associated with antitumor responses to the combination as assessed by the Fanconi Anemia Triple Stain Immunofluorescence assay, performed on archived paraffin embedded tumor tissues.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response</measure>
    <time_frame>3 years</time_frame>
    <description>Duration of response (DoR), defined as time from documentation of tumor response to disease progression</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">48</enrollment>
  <condition>Cervical Cancer</condition>
  <condition>Cervical Carcinoma</condition>
  <arm_group>
    <arm_group_label>Treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>PD-1 inhibitor pembrolizumab, in combination with the PARP inhibitor olaparib</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>pembrolizumab</intervention_name>
    <description>PD-1 inhibitor pembrolizumab, 200mg intravenously (IV) every 3 weeks</description>
    <arm_group_label>Treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>olaparib</intervention_name>
    <description>PARP inhibitor olaparib 300 mg orally, twice daily (BID)</description>
    <arm_group_label>Treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Female participants who are at least 18 years of age on the day of signing informed&#xD;
             consent with histologically confirmed diagnosis of cervical carcinoma will be enrolled&#xD;
             in this study.&#xD;
&#xD;
          2. Cervical cancer is a disease of the female genital tract. No male patients will be&#xD;
             enrolled.&#xD;
&#xD;
          3. A female participant is eligible to participate if she is not pregnant (see Appendix&#xD;
             3), not breastfeeding, and at least one of the following conditions applies:&#xD;
&#xD;
               1. Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR&#xD;
&#xD;
               2. A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the&#xD;
                  treatment period and for at least 120 days after the last dose of study&#xD;
                  treatment.&#xD;
&#xD;
          4. Participant must have recurrent cervical cancer and have a low potential for cure with&#xD;
             radiation therapy or surgery alone and:&#xD;
&#xD;
             a. May have received up to 2 prior chemotherapy regimens. Platinum sensitizing agents&#xD;
             for radiation therapy are considered a chemotherapy regimen.&#xD;
&#xD;
          5. The participant (or legally acceptable representative if applicable) provides written&#xD;
             informed consent for the trial, which includes compliance with the requirements and&#xD;
             restrictions listed in the informed consent form (ICF) and this protocol.&#xD;
&#xD;
          6. Have measurable disease based on RECIST 1.1. Lesions situated in a previously&#xD;
             irradiated area are considered measurable if progression has been demonstrated in such&#xD;
             lesions.&#xD;
&#xD;
          7. Have provided archival tumor tissue sample or newly obtained core or excisional biopsy&#xD;
             of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE)&#xD;
             tissue blocks are preferred to slides. Newly obtained biopsies are preferred to&#xD;
             archived tissue.&#xD;
&#xD;
          8. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.&#xD;
             Evaluation of ECOG is to be performed prior to the first dose of treatment.&#xD;
&#xD;
          9. Patient's life expectancy ≥ 16 weeks.&#xD;
&#xD;
         10. Have adequate organ function as defined in the following table (Table 1). Specimens&#xD;
             must be collected within 10 days prior to the start of study treatment. Before&#xD;
             patients can be enrolled, they must have normal laboratory values as outlined in Table&#xD;
             1. Labs must also fall within normal limits prior to infusion.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. A WOCBP who has a positive urine pregnancy test within 72 hours prior to the first&#xD;
             dose of treatment (see Appendix 3). If the urine test is positive or cannot be&#xD;
             confirmed as negative, a serum pregnancy test will be required.&#xD;
&#xD;
          2. Note: in the event that 72 hours have elapsed between the screening pregnancy test and&#xD;
             the first dose of study treatment, another pregnancy test (urine or serum) must be&#xD;
             performed and must be negative in order for subject to start receiving study&#xD;
             medication.&#xD;
&#xD;
          3. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with&#xD;
             an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4,&#xD;
             OX 40, CD137).&#xD;
&#xD;
          4. Has received prior systemic anti-cancer therapy including investigational agents&#xD;
             within 4 weeks prior to the first dose of treatment.&#xD;
&#xD;
          5. Has received prior radiotherapy within 2 weeks of start of study intervention.&#xD;
             Participants must have recovered from all radiation-related toxicities, not require&#xD;
             corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted&#xD;
             for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.&#xD;
&#xD;
          6. Has received a live vaccine within 30 days prior to the first dose of study drug.&#xD;
             Examples of live vaccines include, but are not limited to, the following: measles,&#xD;
             mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus&#xD;
             Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection&#xD;
             are generally killed virus vaccines and are allowed; however, intranasal influenza&#xD;
             vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.&#xD;
&#xD;
          7. Is currently participating in or has participated in a study of an investigational&#xD;
             agent or has used an investigational device within 4 weeks prior to the first dose of&#xD;
             study intervention.&#xD;
&#xD;
          8. Concomitant use of known strong CYP3A inhibitors (eg. itraconazole, telithromycin,&#xD;
             clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir,&#xD;
             saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg.&#xD;
             ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout&#xD;
             period prior to starting olaparib is 2 weeks.&#xD;
&#xD;
          9. Concomitant use of known strong (eg. phenobarbital, enzalutamide, phenytoin,&#xD;
             rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or&#xD;
             moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil). The required washout&#xD;
             period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3&#xD;
             weeks for other agents.&#xD;
&#xD;
         10. Major surgery within 2 weeks of starting study treatment and patients must have&#xD;
             recovered from any effects of any major surgery.&#xD;
&#xD;
         11. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy&#xD;
             (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of&#xD;
             immunosuppressive therapy within 7 days prior to the first dose of study drug.&#xD;
&#xD;
         12. Has a history of a second malignancy, unless potentially curative treatment has been&#xD;
             completed with no evidence of malignancy for ≥5 years except: adequately treated&#xD;
             non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal&#xD;
             carcinoma in situ (DCIS), Stage 1, grade 1 endometrial carcinoma.&#xD;
&#xD;
         13. Has known active CNS metastases and/or carcinomatous meningitis. Participants with&#xD;
             previously treated brain metastases may participate provided they are radiologically&#xD;
             stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging&#xD;
             (note that the repeat imaging should be performed during study screening), clinically&#xD;
             stable and without requirement of steroid treatment for at least 14 days prior to&#xD;
             first dose of study intervention.&#xD;
&#xD;
             Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence&#xD;
             of brain metastases is not required. The patient can receive a stable dose of&#xD;
             corticosteroids before and during the study as long as these were started at least 4&#xD;
             weeks prior to treatment. Patients with spinal cord compression unless considered to&#xD;
             have received definitive treatment for this and evidence of clinically stable disease&#xD;
             for 28 days.&#xD;
&#xD;
         14. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients,&#xD;
             or patients with a known hypersensitivity to olaparib or any of the excipients of the&#xD;
             product.&#xD;
&#xD;
         15. 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 (eg., thyroxine, insulin, or physiologic corticosteroid&#xD;
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a&#xD;
             form of systemic treatment and is allowed.&#xD;
&#xD;
         16. Has a history of (non-infectious) pneumonitis that required steroids or has current&#xD;
             pneumonitis.&#xD;
&#xD;
         17. Has an active infection requiring systemic therapy.&#xD;
&#xD;
         18. Has a known history of Human Immunodeficiency Virus (HIV) infection. Note: No HIV&#xD;
             testing is required unless mandated by local health authority. Immunocompromised&#xD;
             patients, e.g., patients who are known to be serologically positive for human&#xD;
             immunodeficiency virus (HIV), solid organ, and hematopoietic transplant patients.&#xD;
&#xD;
         19. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg]&#xD;
             reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is&#xD;
             detected) infection.&#xD;
&#xD;
         20. Has a known history of active TB (Bacillus Tuberculosis).&#xD;
&#xD;
         21. Has a history or current evidence of any condition, therapy, or laboratory abnormality&#xD;
             that might confound the results of the study, interfere with the subject's&#xD;
             participation for the full duration of the study, or is not in the best interest of&#xD;
             the subject to participate, in the opinion of the treating investigator.&#xD;
&#xD;
             Patients considered a poor medical risk due to a serious, uncontrolled medical&#xD;
             disorder, non-malignant systemic disease or active, uncontrolled infection. Examples&#xD;
             include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3&#xD;
             months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal&#xD;
             cord compression, superior vena cava syndrome, extensive interstitial bilateral lung&#xD;
             disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric disorder&#xD;
             that interferes with the requirements of the trial or prohibits obtaining informed&#xD;
             consent.&#xD;
&#xD;
         22. Has known psychiatric or substance abuse disorders that would interfere with&#xD;
             cooperation with the requirements of the trial.&#xD;
&#xD;
         23. Is pregnant or breastfeeding or expecting to conceive children within the projected&#xD;
             duration of the study, starting with the screening visit through 120 days after the&#xD;
             last dose of trial treatment.&#xD;
&#xD;
         24. Has had an allogenic tissue/solid organ/bone marrow transplant or double umbilical&#xD;
             cord blood transplantation (dUCBT).&#xD;
&#xD;
         25. Resting ECG and EKG indicating uncontrolled, potentially reversible cardiac&#xD;
             conditions, as judged by the investigator (eg., unstable ischemia, uncontrolled&#xD;
             symptomatic arrhythmia, congestive heart failure, QTcF prolongation &gt;500 ms,&#xD;
             electrolyte disturbances, etc.), or patients with congenital long QT syndrome.&#xD;
&#xD;
         26. Persistent toxicities (&gt;Common Terminology Criteria for Adverse Event (CTCAE) V. 5.0&#xD;
             grade 2) caused by previous cancer therapy, excluding alopecia.&#xD;
&#xD;
         27. Patients with myelodysplastic syndrome/acute myeloid leukemia or with features&#xD;
             suggestive of Myelodysplastic syndromes and acute myeloid leukemia (MDS/AML).&#xD;
&#xD;
         28. Patients unable to swallow orally administered medication and patients with&#xD;
             gastrointestinal disorders likely to interfere with absorption of the study&#xD;
             medication.&#xD;
&#xD;
         29. Whole blood transfusions in the last 120 days prior to entry to the study (packed red&#xD;
             blood cells and platelet transfusions are acceptable).&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Cervical cancer is a disease of the female genital tract. No male patients will be enrolled.</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</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>
  <overall_contact>
    <last_name>John P. Diaz, MD</last_name>
    <phone>786-596-2000</phone>
    <email>JohnPD@baptisthealth.net</email>
  </overall_contact>
  <location>
    <facility>
      <name>Miami Cancer Institute</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33176</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>John P Diaz, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Miami Cancer Institute at Plantation</name>
      <address>
        <city>Plantation</city>
        <state>Florida</state>
        <zip>33324</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>John Diaz, MD</last_name>
    </contact>
    <investigator>
      <last_name>John Diaz, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://baptisthealth.net/cancer-care/home</url>
    <description>Miami Cancer Institute</description>
  </link>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>July 20, 2020</study_first_submitted>
  <study_first_submitted_qc>July 20, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 23, 2020</study_first_posted>
  <last_update_submitted>April 14, 2023</last_update_submitted>
  <last_update_submitted_qc>April 14, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Uterine Cervical Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pembrolizumab</mesh_term>
    <mesh_term>Olaparib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>There is not a plan to make it available</ipd_description>
  </patient_data>
  <!-- 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/NCT04483544
org study id: 2019-JEK-DIA-001
nct id: NCT04483544
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The study is a non-randomized, open-label phase II clinical trial to test the investigational
      combination of the drug pembrolizumab with the drug olaparib in patients diagnosed with
      advanced or recurrent cervical carcinoma after standard chemotherapy.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: PD-1 inhibitor pembrolizumab, in combination with the PARP inhibitor olaparib
primary purpose: Treatment
masking: None (Open Label)
measure: Immune overall response rate
time frame: 3 years
description: Overall objective Response Rate by Immune Response Evaluation Criteria in Solid Tumors (iRECIST) criteria (iORR)
measure: Progression Free Survival
time frame: 3 years
description: Defined among all treated patients as the time from first dose of study drug until the first date of either disease progression or death due to any cause
measure: Number of patient reporting treatment-emergent adverse events (TEAEs)
time frame: 3 years
description: The number of patients reporting treatment emergent adverse events (TEAEs) defined as an AE that occurs or worsens in the period extending from the first dose of study drug to 30 days after the last dose of study drug in this study
measure: Number of patients with baseline tumor deficiencies
time frame: baseline
description: The number of patients with baseline tumor deficiencies in the Fanconi Anemia pathway associated with antitumor responses to the combination as assessed by the Fanconi Anemia Triple Stain Immunofluorescence assay, performed on archived paraffin embedded tumor tissues.
measure: Duration of response
time frame: 3 years
description: Duration of response (DoR), defined as time from documentation of tumor response to disease progression
arm group label: Treatment
arm group type: Experimental
description: PD-1 inhibitor pembrolizumab, in combination with the PARP inhibitor olaparib
intervention type: Drug
intervention name: pembrolizumab
description: PD-1 inhibitor pembrolizumab, 200mg intravenously (IV) every 3 weeks
arm group label: Treatment
intervention type: Drug
intervention name: olaparib
description: PARP inhibitor olaparib 300 mg orally, twice daily (BID)
arm group label: Treatment
criteria: 
gender: Female
gender based: Yes
gender description: Cervical cancer is a disease of the female genital tract. No male patients will be enrolled.
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: John P. Diaz, MD
role: Principal Investigator
affiliation: Miami Cancer Institute at Baptist Health Inc.
last name: John P. Diaz, MD
phone: 786-596-2000
email: JohnPD@baptisthealth.net
facility: 
status: Recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
country: United States
url: https://baptisthealth.net/cancer-care/home
description: Miami Cancer Institute
responsible party type: Sponsor
mesh term: Uterine Cervical Neoplasms
mesh term: Pembrolizumab
mesh term: Olaparib
sharing ipd: No
ipd description: There is not a plan to make it available