Clinical Trials /

Pembrolizumab and Olaparib in Cervical Cancer Patients

NCT04483544

Description:

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.

Related Conditions:
  • Cervical Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab and Olaparib in Cervical Cancer Patients
  • Official Title: Immunotherapy in Combination With PARP Inhibition in Advanced Cervical Cancer Patients Functionally Competent or Deficient for the Fanconi Anemia Repair Pathway

Clinical Trial IDs

  • ORG STUDY ID: 2019-JEK-DIA-001
  • NCT ID: NCT04483544

Conditions

  • Cervical Cancer
  • Cervical Carcinoma

Interventions

DrugSynonymsArms
pembrolizumabTreatment
olaparibTreatment

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
TreatmentExperimentalPD-1 inhibitor pembrolizumab, in combination with the PARP inhibitor olaparib
  • pembrolizumab
  • olaparib

Eligibility Criteria

        Inclusion Criteria:

          1. Female participants who are at least 18 years of age on the day of signing informed
             consent with histologically confirmed diagnosis of cervical carcinoma will be enrolled
             in this study.

          2. Cervical cancer is a disease of the female genital tract. No male patients will be
             enrolled.

          3. A female participant is eligible to participate if she is not pregnant (see Appendix
             3), not breastfeeding, and at least one of the following conditions applies:

               1. Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR

               2. A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the
                  treatment period and for at least 120 days after the last dose of study
                  treatment.

          4. Participant must have recurrent cervical cancer and have a low potential for cure with
             radiation therapy or surgery alone and:

             a. May have received up to 2 prior chemotherapy regimens. Platinum sensitizing agents
             for radiation therapy are considered a chemotherapy regimen.

          5. The participant (or legally acceptable representative if applicable) provides written
             informed consent for the trial, which includes compliance with the requirements and
             restrictions listed in the informed consent form (ICF) and this protocol.

          6. Have measurable disease based on RECIST 1.1. Lesions situated in a previously
             irradiated area are considered measurable if progression has been demonstrated in such
             lesions.

          7. Have provided archival tumor tissue sample or newly obtained core or excisional biopsy
             of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE)
             tissue blocks are preferred to slides. Newly obtained biopsies are preferred to
             archived tissue.

          8. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
             Evaluation of ECOG is to be performed prior to the first dose of treatment.

          9. Patient's life expectancy ≥ 16 weeks.

         10. Have adequate organ function as defined in the following table (Table 1). Specimens
             must be collected within 10 days prior to the start of study treatment. Before
             patients can be enrolled, they must have normal laboratory values as outlined in Table
             1. Labs must also fall within normal limits prior to infusion.

        Exclusion Criteria:

          1. A WOCBP who has a positive urine pregnancy test within 72 hours prior to the first
             dose of treatment (see Appendix 3). If the urine test is positive or cannot be
             confirmed as negative, a serum pregnancy test will be required.

          2. Note: in the event that 72 hours have elapsed between the screening pregnancy test and
             the first dose of study treatment, another pregnancy test (urine or serum) must be
             performed and must be negative in order for subject to start receiving study
             medication.

          3. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with
             an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4,
             OX 40, CD137).

          4. Has received prior systemic anti-cancer therapy including investigational agents
             within 4 weeks prior to the first dose of treatment.

          5. Has received prior radiotherapy within 2 weeks of start of study intervention.
             Participants must have recovered from all radiation-related toxicities, not require
             corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted
             for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.

          6. Has received a live vaccine within 30 days prior to the first dose of study drug.
             Examples of live vaccines include, but are not limited to, the following: measles,
             mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus
             Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection
             are generally killed virus vaccines and are allowed; however, intranasal influenza
             vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.

          7. Is currently participating in or has participated in a study of an investigational
             agent or has used an investigational device within 4 weeks prior to the first dose of
             study intervention.

          8. Concomitant use of known strong CYP3A inhibitors (eg. itraconazole, telithromycin,
             clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir,
             saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg.
             ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout
             period prior to starting olaparib is 2 weeks.

          9. Concomitant use of known strong (eg. phenobarbital, enzalutamide, phenytoin,
             rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or
             moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil). The required washout
             period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3
             weeks for other agents.

         10. Major surgery within 2 weeks of starting study treatment and patients must have
             recovered from any effects of any major surgery.

         11. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
             (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
             immunosuppressive therapy within 7 days prior to the first dose of study drug.

         12. Has a history of a second malignancy, unless potentially curative treatment has been
             completed with no evidence of malignancy for ≥5 years except: adequately treated
             non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal
             carcinoma in situ (DCIS), Stage 1, grade 1 endometrial carcinoma.

         13. Has known active CNS metastases and/or carcinomatous meningitis. Participants with
             previously treated brain metastases may participate provided they are radiologically
             stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging
             (note that the repeat imaging should be performed during study screening), clinically
             stable and without requirement of steroid treatment for at least 14 days prior to
             first dose of study intervention.

             Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence
             of brain metastases is not required. The patient can receive a stable dose of
             corticosteroids before and during the study as long as these were started at least 4
             weeks prior to treatment. Patients with spinal cord compression unless considered to
             have received definitive treatment for this and evidence of clinically stable disease
             for 28 days.

         14. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients,
             or patients with a known hypersensitivity to olaparib or any of the excipients of the
             product.

         15. Has active autoimmune disease that has required systemic treatment in the past 2 years
             (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
             drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
             form of systemic treatment and is allowed.

         16. Has a history of (non-infectious) pneumonitis that required steroids or has current
             pneumonitis.

         17. Has an active infection requiring systemic therapy.

         18. Has a known history of Human Immunodeficiency Virus (HIV) infection. Note: No HIV
             testing is required unless mandated by local health authority. Immunocompromised
             patients, e.g., patients who are known to be serologically positive for human
             immunodeficiency virus (HIV), solid organ, and hematopoietic transplant patients.

         19. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg]
             reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is
             detected) infection.

         20. Has a known history of active TB (Bacillus Tuberculosis).

         21. Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the study, interfere with the subject's
             participation for the full duration of the study, or is not in the best interest of
             the subject to participate, in the opinion of the treating investigator.

             Patients considered a poor medical risk due to a serious, uncontrolled medical
             disorder, non-malignant systemic disease or active, uncontrolled infection. Examples
             include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3
             months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal
             cord compression, superior vena cava syndrome, extensive interstitial bilateral lung
             disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric disorder
             that interferes with the requirements of the trial or prohibits obtaining informed
             consent.

         22. Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial.

         23. Is pregnant or breastfeeding or expecting to conceive children within the projected
             duration of the study, starting with the screening visit through 120 days after the
             last dose of trial treatment.

         24. Has had an allogenic tissue/solid organ/bone marrow transplant or double umbilical
             cord blood transplantation (dUCBT).

         25. Resting ECG and EKG indicating uncontrolled, potentially reversible cardiac
             conditions, as judged by the investigator (eg., unstable ischemia, uncontrolled
             symptomatic arrhythmia, congestive heart failure, QTcF prolongation >500 ms,
             electrolyte disturbances, etc.), or patients with congenital long QT syndrome.

         26. Persistent toxicities (>Common Terminology Criteria for Adverse Event (CTCAE) V. 5.0
             grade 2) caused by previous cancer therapy, excluding alopecia.

         27. Patients with myelodysplastic syndrome/acute myeloid leukemia or with features
             suggestive of Myelodysplastic syndromes and acute myeloid leukemia (MDS/AML).

         28. Patients unable to swallow orally administered medication and patients with
             gastrointestinal disorders likely to interfere with absorption of the study
             medication.

         29. Whole blood transfusions in the last 120 days prior to entry to the study (packed red
             blood cells and platelet transfusions are acceptable).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Immune overall response rate
Time Frame:3 years
Safety Issue:
Description:Overall objective Response Rate by Immune Response Evaluation Criteria in Solid Tumors (iRECIST) criteria (iORR)

Secondary Outcome Measures

Measure:Progression Free Survival
Time Frame:3 years
Safety Issue:
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
Safety Issue:
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
Safety Issue:
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
Safety Issue:
Description:Duration of response (DoR), defined as time from documentation of tumor response to disease progression

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Baptist Health South Florida

Last Updated

October 15, 2020