Clinical Trials /

Pembrolizumab Plus Olaparib in Patients With Recurrent Cervical Cancer

NCT04641728

Description:

This trial is a multicenter, single-arm, phase 2 study of pembrolizumab in combination with olaparib in recurrent or metastatic cervical cancer patients who had disease progression during or after platinum-based chemotherapy.

Related Conditions:
  • Cervical Adenocarcinoma
  • Cervical Adenosquamous Carcinoma
  • Cervical Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab Plus Olaparib in Patients With Recurrent Cervical Cancer
  • Official Title: A Phase 2 Study of Pembrolizumab in Combination With Olaparib in Patients With Recurrent or Metastatic Cervical Cancer Who Had Disease Progression During or After Platinum-based Chemotherapy

Clinical Trial IDs

  • ORG STUDY ID: GOTIC-025
  • NCT ID: NCT04641728

Conditions

  • Cervical Cancer

Interventions

DrugSynonymsArms
PembrolizumabKEYTRUDApembrolizumab plus olaparib
OlaparibLYNPARZApembrolizumab plus olaparib

Purpose

This trial is a multicenter, single-arm, phase 2 study of pembrolizumab in combination with olaparib in recurrent or metastatic cervical cancer patients who had disease progression during or after platinum-based chemotherapy.

Detailed Description

      This trial is a multicenter, single-arm, phase 2 study of pembrolizumab in combination with
      olaparib in recurrent or metastatic cervical cancer patients who had disease progression
      during or after platinum-based chemotherapy.

      This study is planned to enroll 28 patients eligible for participation from multiple study
      sites in Japan.
    

Trial Arms

NameTypeDescriptionInterventions
pembrolizumab plus olaparibExperimentalUntil RECIST-based confirmation of progressive disease (PD), death, manifestation of intolerable toxicity, or participant withdrawal from the study, study participants will continue intravenous infusion of pembrolizumab 200 mg every three weeks (Q3W) in combination with oral olaparib 300 mg twice daily (BID) (combination therapy)
  • Pembrolizumab
  • Olaparib

Eligibility Criteria

        Inclusion Criteria:

          1. Participants who are at least 20 years of age on the day of signing informed consent
             with histologically confirmed, recurrent or metastatic cervical cancer (squamous cell
             carcinoma, adenocarcinoma or adenosquamous cell carcinoma)

          2. Participants with confirmed disease progression during or after platinum-based
             chemotherapy 1 or intolerant to or ineligible for platinum-based chemotherapy or
             ineligible participants

          3. Participants with measurable disease based on RECIST 1.1 at screening

          4. Participant is able to provide a core or excisional biopsy of a tumor lesion for
             testing of PD-L1 status, etc

          5. Participants with Eastern Cooperative Oncology Group (ECOG) PS of 0 to 1 upon the
             screening

          6. Participants who may be expected to survive at least for 12 weeks after the first dose
             of study drug as determined by the principal investigator or a subinvestigator

          7. Have adequate organ function

        Exclusion Criteria:

          1. 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).

          2. Has received prior systemic anti-cancer therapy including investigational agents
             within 4 weeks prior to the enrollment.

          3. Has received prior radiotherapy within 2 weeks prior to the enrollment. 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.

          4. Has received a live vaccine within 28 days prior to the enrollment. 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.

          5. 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 enrollment.

          6. 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 enrollment.

          7. Has a second malignancy advanced or requiring treatment within the past 3 years.The
             time requirement does not apply to participants who underwent successful definitive
             resection of basal cell carcinoma of the skin, in situ cancers (e.g. in situ breast
             carcinomas).

          8. 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 the
             enrollment.

          9. Has severe hypersensitivity (≥Grade 3) to the study drug and/or any of its excipients.

         10. 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 participants can be enrolled in the trial.

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

         12. Has an active infection requiring systemic therapy.

         13. Has a known history of Human Immunodeficiency Virus (HIV) infection.

         14. 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.

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

         16. 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.

         17. Participant has received colony-stimulating factors (eg, granulocyte colony
             stimulating factor [G-CSF], granulocyte macrophage colony-stimulating factor [GM-CSF]
             or recombinant erythropoietin) within 2 weeks prior to the enrollment.

         18. Participant with clinically serious cardiovascular/cerebrovascular diseases including
             the following: cerebrovascular accident/stroke (less than 6 month prior to
             enrollment), myocardial infarction (less than 6 month prior to enrollment), unstable
             angina, congestive heart failure (the New York Heart Association (NYHA) Functional
             Classification Class 2 or severer), or serious arrhythmia. In addition, participants
             with history of bleeding tendency or recent major bleeding event in whom study drug
             administration carries higher risks as determined by the principal investigator will
             be excluded.

         19. Participant who have acute or chronic disease with severe and/or clinical symptoms
             which may compromise the tolerance to this study or competence to consistently follow
             the study procedures as determined by the principal investigator

         20. Participants with medical history of receiving all the PARP inhibitors

         21. Participant is currently receiving either strong (eg, itraconazole, telithromycin,
             clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir,
             saquinavir, nelfinavir, boceprevir, telaprevir) or moderate (eg. ciprofloxacin,
             erythromycin, diltiazem, fluconazole, verapamil) inhibitors of cytochrome P450
             (CYP)3A4 that cannot be discontinued before the study drug initiation. The required
             washout period prior to starting olaparib is 2 weeks.

         22. Participant is currently receiving either strong (eg, phenobarbital, enzalutamide,
             phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine, and St
             John's Wort) or moderate (eg. bosentan, efavirenz, modafinil) inducers of CYP3A4 that
             cannot be discontinued before the study drug initiation. The required washout period
             prior to starting olaparib is 5 weeks for phenobarbital and 3 weeks for other agents.

         23. Participant is either unable to swallow orally administered medication or has a
             gastrointestinal disorder affecting absorption (eg, gastrectomy, partial bowel
             obstruction, malabsorption).

         24. Participant has resting electrocardiogram (ECG) 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 participant has congenital long QT syndrome.

         25. Has a major surgery history 4 weeks prior to the enrollment (e.g.: diagnostic biopsy
             is not regarded as the major surgery)

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

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

         28. Participant, in the judgement of the investigator, is unlikely to comply with the
             study procedures, restrictions, and requirements of the study.

         29. Participant has had an allogenic tissue/solid organ transplant
      
Maximum Eligible Age:N/A
Minimum Eligible Age:20 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate
Time Frame:3 years
Safety Issue:
Description:Objective Response Rate (ORR) will be evaluated after pembrolizumab in combination with olaparib based on RECIST 1.1.

Secondary Outcome Measures

Measure:Objective Response Rate on iRECIST
Time Frame:3 years
Safety Issue:
Description:To assess ORR after administration of pembrolizumab in combination with olaparib based on iRECIST.
Measure:Duration of response
Time Frame:3 years
Safety Issue:
Description:To assess duration of response (DOR) after administration of pembrolizumab in combination with olaparib based on RECIST 1.1 and iRECIST.
Measure:Durable response rate
Time Frame:3 years
Safety Issue:
Description:To assess durable response rate (DRR) after administration of pembrolizumab in combination with olaparib based on RECIST 1.1 and iRECIST
Measure:Percentage of patients with response to administration of pembrolizumab in combination with olaparib for 6 months and longer
Time Frame:3 years
Safety Issue:
Description:To assess the percentage of patients with response to administration of pembrolizumab in combination with olaparib for 6 months and longer based on RECIST 1.1 and iRECIST
Measure:PFS after administration of pembrolizumab in combination with olaparib
Time Frame:3 years
Safety Issue:
Description:To assess progression-free survival (PFS) after administration of pembrolizumab in combination with olaparib based on RECIST 1.1 and iRECIST
Measure:Incidence of treatment-related adverse events after administration of pembrolizumab in combination with olaparib
Time Frame:3 years
Safety Issue:
Description:To assess the number of participants with treatment-related adverse events after administration of pembrolizumab in combination with olaparib based on CTCAE v5.0
Measure:Objective Response Rate based on PD-L1 status
Time Frame:3 years
Safety Issue:
Description:ORR will be evaluated after pembrolizumab in combination with olaparib stratified by PD-L1 status based on RECIST 1.1 and iRECIST.
Measure:Duration of response based on PD-L1 status
Time Frame:3 years
Safety Issue:
Description:To assess DOR after administration of pembrolizumab in combination with olaparib stratified by PD-L1 status based on RECIST 1.1 and iRECIST.
Measure:Durable response rate based on PD-L1 status
Time Frame:3 years
Safety Issue:
Description:To assess DRR after administration of pembrolizumab in combination with olaparib stratified by PD-L1 status based on RECIST 1.1 and iRECIST.
Measure:PFS based on PD-L1 status
Time Frame:3 years
Safety Issue:
Description:To assess PFS after administration of pembrolizumab in combination with olaparib stratified by PD-L1 status based on RECIST 1.1 and iRECIST.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Saitama Medical University International Medical Center

Trial Keywords

  • cervical cancer
  • pembrolizumab
  • olaparib

Last Updated

June 24, 2021