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

Официальное название

A Single-arm Phase II Study of Olaparib Maintenance With Pembrolizumab & Bevacizumab in BRCA Non-mutated Patients With Platinum-sensitive Recurrent Ovarian Cancer (OPEB-01)

Обзор

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.

Подробное описание

'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)

Вмешательства

• Препарат Olaparib-Pembrolizumab-Bevacizumab
  * 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)

Первичные конечные точки

• progression-free survival(6 months PFS rate) [Срок оценки: 6 months]

Вторичные конечные точки (5)

• Overall survival (OS) [Срок оценки: Up to 1year]
• Time to tumour progression (TTP) [Срок оценки: Up to 1year]
• Time to first subsequent treatment(or death) [Срок оценки: The date of first documented first subsequent treatment or date of death, assessed up to 72 months]
• Time to second subsequent treatment [Срок оценки: The date of first documented second subsequent treatment assessed up to 72 months]
• progression-free survival [Срок оценки: Up to 1year]

Критерии участия

Критерии включения

• 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:

• ANC≥1500/µL
• PLT≥100 000/µL
• Hemoglobin≥9.0 g/dL or ≥5.6 mmol/L
• Creatinine≤1.5 × ULN or calculated creatinine clearance≥30 mL/min for participant with creatinine levels >1.5 × institutional ULN
• Total bilirubin≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN
• AST (SGOT) and ALT (SGPT)≤2.5 × ULN (≤5 × ULN for participants with liver metastases)
• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

South Korea · 1 центр

• Yonsei Severance Hospital — Seoul

Публикации

• Lee YJ, Lim MC, Kim BG, Ngoi NY, Choi CH, Park SY, Tan DS, Go Y, Lee JY. A single-arm phase II study of olaparib maintenance with pembrolizumab and bevacizumab in BRCA non-mutated patients with platinum-sensitive recurrent ovarian cancer (OPEB-01). J Gynecol Oncol. 2021 Mar;32(2):e31. doi: 10.3802/jgo.2021.32.e31. Epub 2021 Jan 27. PMID 33559413

Идентификаторы

NCT: NCT04361370 · 4-2020-0386

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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