Olaparib Monotherapy and Olaparib + Pembrolizumab Combination Therapy for Ovarian Cancer

NCT ID: NCT04417192

Last Updated: 2023-07-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-01
• Study Completion Date: 2023-06-30

Brief Summary

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).

Conditions

Ovarian Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Olaparib or Olaparib Plus Pembrolizumab

Cohort 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.

Group Type: EXPERIMENTAL

Olaparib

Intervention Type: DRUG

Olaparib will be administered at a dose of 300mg as oral dose, twice a day.

Pembrolizumab

Intervention Type: DRUG

Pembrolizumab will be administered at a dose of 200mg as a 30-minutes IV infusion, Q3W (25 minutes to 40 minutes are acceptable).

Interventions

Olaparib

Olaparib will be administered at a dose of 300mg as oral dose, twice a day.

Intervention Type: DRUG

Pembrolizumab

Pembrolizumab will be administered at a dose of 200mg as a 30-minutes IV infusion, Q3W (25 minutes to 40 minutes are acceptable).

Intervention Type: DRUG

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.

• Minimum Eligible Age: 20 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

National Cancer Center Hospital East

OTHER

Sponsor Role: lead

Responsible Party

Toru Mukohara

Chief of Breast and Medical Oncology Division

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

National Cancer Center Hospital East

Kashiwa, Chiba, Japan

National Hospital Organization Shikoku Cancer Center

Matsuyama, Ehime, Japan

Kurume University Hospital

Kurume, Fukuoka, Japan

Countries

Japan

Other Identifiers

EPOC1903

Identifier Type: -

Identifier Source: org_study_id