Olaparib Maintenance With Pembrolizumab & Bevacizumab in BRCA Non-mutated Patients With Platinum-sensitive Recurrent Ovarian Cancer

Phase 2

• Conditions: Platinum-sensitive Recurrent BRCA Wild Type Ovarian Cancer
• Interventions: Drug: Olaparib-Pembrolizumab-Bevacizumab

• Registration Number: NCT04361370
• Lead Sponsor: Yonsei University

Brief Summary

This study is phase II, open label, clinical trial to determine the efficacy of Olaparib maintenance with Bevacizumab and Pembrolizumab by assessment progression-free survival(6 months PFS rate) in BRCA non-mutated patients with platinum-sensitive recurrent ovarian cancer.

Detailed Description

'This is a Phase II, open-label, non-randomized, multi-center study assessing the efficacy and safety of Olaparib maintenance with Bevacizumab and Pembrolizumab in subjects with platinum-sensitive who have received prior of platinum-based chemotherapy. The study will assess the effectiveness of progression-free survival(6 months PFS rate) as determined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. The subject will be treated to until disease progression as below:

* Maintenance : Olaparib 300mg (twice daily \[BID\])

* Pembrolizumab 200mg every 3 weeks (Q3W) from 2nd infusion for up to 35 infusions

* Bevacizumab 15mg/kg or 7.5mg/kg every 3 weeks (Q3W)

Study Timeline

• Study First Submitted: 2020-04-19
• Study First Submitted QC: 2020-04-22
• Study First Posted: 2020-04-24
• Study Start: 2020-10-28
• Status Verified: 2021-04
• Last Update Submitted: 2021-04-14
• Last Update Posted: 2021-04-19
• Primary Completion: 2026-05
• Study Completion: 2026-08

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: Female
• Target Recruitment: 44

Inclusion Criteria

• Participant has histologically confirmed diagnosis of high-grade predominantly serous, endometrioid, carcinosarcoma, mixed mullerian with high-grade serous component, clear cell, or low-grade serous OC, primary peritoneal cancer, or fallopian tube cancer will be enrolled in this study (only up to 8 patients with clear cell carcinoma will be included and mucinous carcinoma will not be included).

• Participant has received 2 previous courses of platinum-containing therapy, and has disease that was considered platinum sensitive following the penultimate (next to last) platinum course (more than 6 months' period between penultimate platinum regimen and progression of disease

• Participant has responded to last the platinum regimen (complete or partial response), remains in response and is enrolled on study within 8 weeks of completion of the last platinum regimen

• Participant is able to provide a newly obtained core or excisional biopsy of a tumor lesion for prospective testing of BRCA 1/2 and PD-L1 status prior to enrollment

• Female participants who are at least 20 years of age and Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Participant has adequate organ function as defined in the following:

  1. ANC≥1500/µL
  2. PLT≥100 000/µL
  3. Hemoglobin≥9.0 g/dL or ≥5.6 mmol/L
  4. Creatinine≤1.5 × ULN or calculated creatinine clearance≥30 mL/min for participant with creatinine levels >1.5 × institutional ULN
  5. Total bilirubin≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN
  6. AST (SGOT) and ALT (SGPT)≤2.5 × ULN (≤5 × ULN for participants with liver metastases)
  7. International normalized ratio (INR) OR prothrombin time (PT), Activated partial thromboplastin time (aPTT)≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants

Exclusion Criteria

• Participant has mucinous, germ cell, or borderline tumor of the ovary
• Participant has a known or suspected deleterious mutation (germline or somatic) in either BRCA1 or BRCA2
• Participant has a history of non-infectious pneumonitis that required treatment with steroids or currently has pneumonitis
• Participant either has myelodysplastic syndrome (MDS)/ acute myeloid leukemia (AML) or has features suggestive of MDS/AML
• Participant has a known additional malignancy that is progressing or has required active treatment within the past 3 years
• Participant has known active CNS metastases and/or carcinomatous meningitis
• Participant has a known history of active TB (Bacillus Tuberculosis)
• Participant 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
• Participant has uncontrolled hypertension, defined as systolic > 140 mmHg or diastolic > 90 mmHg documented by 2 blood pressure readings taken at least 1 hour apart
• Participant has a history of hemorrhage, hemoptysis or active gastrointestinal bleeding within 6 months prior to randomization

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment group	Olaparib-Pembrolizumab-Bevacizumab	BRCA mutation wild type, non-mucinous , platinum-sensitive recurrent ovarian cancer

Primary Outcome Measures

Name	Time	Method
progression-free survival(6 months PFS rate)	6 months	To determine the clinical effectiveness of the study treatment assessed using progression free survival(6months) according to RECIST v1.1 criteria (Investigator determined)

Secondary Outcome Measures

Name	Time	Method
Overall survival (OS)	Up to 1year
Time to first subsequent treatment(or death)	The date of first documented first subsequent treatment or date of death, assessed up to 72 months
Time to tumour progression (TTP)	Up to 1year
Time to second subsequent treatment	The date of first documented second subsequent treatment assessed up to 72 months
progression-free survival	Up to 1year

Trial Locations

Locations (1)

Yonsei Severance Hospital; 🇰🇷 Seoul, Korea, Republic of