Clinical Trials /

Olaparib Monotherapy and Olaparib + Pembrolizumab Combination Therapy for Ovarian Cancer

NCT04417192

Description:

To evaluate the efficacy and safety of preoperative olaparib monotherapy and preoperative olaparib plus pembrolizumab combination therapy in patients with untreated stage III, IV high-grade serous or Grade 3 endometrioid ovarian cancer with Homologous Recombination Deficiency (HRD) positivity.

Related Conditions:
  • Fallopian Tube Endometrioid Adenocarcinoma
  • High Grade Fallopian Tube Serous Adenocarcinoma
  • Ovarian Endometrioid Adenocarcinoma
  • Ovarian Serous Adenocarcinoma
  • Primary Peritoneal Endometrioid Adenocarcinoma
  • Primary Peritoneal Serous Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Olaparib Monotherapy and Olaparib + Pembrolizumab Combination Therapy for Ovarian Cancer
  • Official Title: A Pilot Study to Evaluate the Efficacy and Safety of Preoperative Olaparib Monotherapy and Preoperative Olaparib Plus Pembrolizumab Combination Therapy in Patients With HRD-Positive Stage III or IV Advanced Epithelial Ovarian/Fallopian Tube/Primary Peritoneal Cancer

Clinical Trial IDs

  • ORG STUDY ID: EPOC1903
  • NCT ID: NCT04417192

Conditions

  • Ovarian Cancer

Interventions

DrugSynonymsArms
OlaparibOlaparib or Olaparib Plus Pembrolizumab
PembrolizumabOlaparib or Olaparib Plus Pembrolizumab

Purpose

To evaluate the efficacy and safety of preoperative olaparib monotherapy and preoperative olaparib plus pembrolizumab combination therapy in patients with untreated stage III, IV high-grade serous or Grade 3 endometrioid ovarian cancer with Homologous Recombination Deficiency (HRD) positivity.

Detailed Description

      To evaluate the efficacy and safety of preoperative olaparib monotherapy and preoperative
      olaparib plus pembrolizumab combination therapy in patients with untreated stage III, IV
      high-grade serous or Grade 3 endometrioid ovarian cancer with HRD positivity. The first
      cohort (Olaparib monotherapy : 10 cases) will be evaluated for the presence or absence of
      immune cell activation, and the tumor reduction effect will be evaluated in the second cohort
      (Olaparib plus pembrolizumab combination therapy : 20 cases).
    

Trial Arms

NameTypeDescriptionInterventions
Olaparib or Olaparib Plus PembrolizumabExperimentalCohort 1 : Olaparib will be administered for 6 weeks before surgery. Cohort 2 : Olaparib and Pembrolizumab will be administered simultaneously for 2 cycles(6 weeks) before surgery.
  • Olaparib
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          1. Has given signed informed consent to participate in the clinical trial of her own
             will.

          2. Is aged 20 years or older on the day of signing the informed consent.

          3. Has been diagnosed with histologically confirmed, Stage III or IV epithelial ovarian,
             fallopian tube, or primary peritoneal cancer by the International Federation of
             Gynecology and Obstetrics (FIGO) staging system (2014), with a histological type of
             high-grade serous or Grade 3 endometrioid carcinoma.

          4. Have measurable disease based on RECIST 1.1.

          5. Is a candidate for debulking surgery.

          6. Has an HRD-positive tumor.

          7. Has an ECOG Performance Status of 0 or 1.

          8. Laboratory test results within 21 days prior to enrollment have met the following
             organ function criteria. However, measurements within 14 days of blood transfusion or
             administration of granulocyte-colony stimulating factor (G-CSF) are excluded.

               -  Neutrophil count ≥ 1,500/mm3

               -  Platelet count ≥ 100,000/mm3

               -  Hemoglobin ≥ 9.0 g/dL

               -  Serum creatinine ≤ 1.5 × ULN, or creatinine clearance ≥ 50 mL/min

               -  T-Bil ≤ 2.0 mg/dL

               -  ALT and AST ≤ 100 U/L (≤ 200 U/L if liver metastasis is present)

          9. A woman of childbearing potential must agree to use contraception after signing the
             informed consent, throughout the study period, and until at least 120 days following
             the last dose of the study drug

        Exclusion Criteria:

          1. Has received previous allogeneic bone-marrow transplantation.

          2. Has concurrent interstitial lung disease/pneumonitis, or a history of (noninfectious)
             interstitial lung disease/pneumonitis that required treatment with steroids.
             Interstitial lung disease/pneumonitis includes radiation pneumonitis.

          3. Has received prior antitumor therapy (e.g., chemotherapy, molecular-targeted therapy,
             therapeutic antibody, endocrine therapy, immunotherapy, and investigational therapy).

          4. Has received surgery under general anesthesia within 28 days prior to enrollment.
             However, surgery to diagnose ovarian/fallopian tube/peritoneal cancer performed under
             general anesthesia is allowed.

          5. Has received radiation or radioactive isotope therapy within 28 days prior to
             enrollment.

          6. Has uncontrolled pericardial effusion, pleural effusion, or peritoneal effusion.

          7. Has a history of cerebral infarction, cerebral hemorrhage, or transient cerebral
             ischemia within 180 days prior to enrollment.

          8. Has a history of deep vein thrombosis or pulmonary embolism.

          9. Is receiving systemic glucocorticoid therapy or systemic immunosuppressive therapy.

         10. Has a history of autoimmune disease.

         11. Is infected with human immunodeficiency virus (HIV).

         12. Is infected with active* hepatitis B or hepatitis C.

             *: Active hepatitis B is defined as HBs antigen positive.

         13. Has a symptomatic infection within 14 days prior to enrollment.

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

         15. Has clinically critical cardiac disease (has a history of myocardial infarction or
             angina pectoris within 180 days prior to enrollment or has New York Heart Association
             [NYHA] class II or higher cardiac failure, uncontrolled arrhythmia, or QTc
             prolongation defined as QTc > 470 msec).

         16. Has active brain metastasis or a tumor causing spinal cord compression.

         17. Is pregnant or breastfeeding.

         18. Has a history of severe allergy, anaphylaxis, or hypersensitivity induced by humanized
             chimeric antibodies.

         19. Is allergic to biologics produced from Chinese hamster ovary (CHO) cells, carboplatin,
             or paclitaxel.

         20. Has a known or suspected active malignancy that is different from the disease of
             interest in the clinical trial or has a history of other malignancy within 3 years
             prior to enrollment. However, cutaneous basal cell carcinoma and cervical carcinoma in
             situ are not part of this exclusion criterion.

         21. Is unwilling to or unable to comply with the protocol.

         22. Is not eligible to enroll in the clinical trial based on the judgment by the
             Investigator or Sub-investigator.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:20 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:6 weeks
Safety Issue:
Description:Objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumours (RECIST) version. 1.1.

Secondary Outcome Measures

Measure:The incidence of adverse events
Time Frame:Up to 30 days after the last dose
Safety Issue:
Description:The incidences and types of adverse events that occur during treatment will be evaluated according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Measure:Chemotherapy response score (CRS)
Time Frame:6 months from the end of registration
Safety Issue:
Description:To evaluate the effect of histopathological treatment on patients with serous carcinoma and metastasis to the omentum. The histopathological treatment effect is determined according to the chemotherapy response score (CRS)
Measure:Progression-free survival (PFS)
Time Frame:6 months from the end of registration
Safety Issue:
Description:PFS is defined as the time from the first dose to the earlier of progression assessed by the Investigator per RECIST v. 1.1 (PD) or clinical criteria, or death due to any cause.
Measure:Overall survival (OS)
Time Frame:6 months from the end of registration
Safety Issue:
Description:OS is defined as the time from the first dose to death due to any cause.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:National Cancer Center Hospital East

Last Updated

June 2, 2020