Phase II Study of Pembrolizumab and Bevacizumab in Combination With Platinum-based Chemotherapy Followed by Pembrolizumab, Bevacizumab and Olaparib in Patients With Platinum-sensitive Recurrent Ovarian Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- Two-year progression-free survival rate
研究概览
简要总结
This trial is a multicenter, single-arm, phase II study evaluating the efficacy of pembrolizumab and bevacizumab in combination with platinum-based chemotherapy (PBC) followed by pembrolizumab, bevacizumab and olaparib as a maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer.This study is planned to enroll eligible 35 patients from multiple study sites in Japan.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Participant is at least 20 years of age on the day of signing informed consent with histologically confirmed epithelial ovarian cancer (excluding borderline ovarian tumor) excluding mucinous carcinoma.
- •Participant has received only one regimen of PBC (3 cycles or more) as prior therapy with clinical CR (determined by negative clinical examination and a normal CA-125 level).
- •Participant has documentation of progressive disease at least 6 months from completion of PBC (platinum-sensitive).
- •Participant with measurable disease based on RECIST 1.1 at screening
- •Participant is able to provide a core or excisional biopsy of a tumor for testing of PD-L1 status, etc.
- •Participant with Eastern Cooperative Oncology Group (ECOG) PS of 0 to 1 at the screening
- •Participant has a life expectancy of at least 12 weeks as determined by the investigators.
- •Participant has adequate organ function.
排除标准
- •A Women of Childbearing Potential (WOCBP) who has a positive urine pregnancy test at screening. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- •Participant 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).
- •Participant has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to the first dose of study drug.
- •Participant has received prior radiotherapy within 2 weeks of the first dose of study drug.
- •Participant has received major surgery within 4 weeks prior to the first dose of study drug.
- •Participant has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
- •Participant 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 first dose of study drug.
- •Participant 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 first dose of study drug.
- •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 severe hypersensitivity (≥Grade 3) to the study treatment and/or any of its excipients.
- •Participant 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).
- •Participant has a history of (non-infectious) pneumonitis/interstitial lung disease that required treatment with steroids or has current pneumonitis/interstitial lung disease.
- •Participant has an active infection requiring systemic therapy.
- •Participant has a known history of Human Immunodeficiency Virus (HIV) infection.
- •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 received colony-stimulating factors (granulocyte colony stimulating factor [G-CSF], granulocyte macrophage colony-stimulating factor [GM-CSF] or recombinant erythropoietin) within 2 weeks prior to the first dose of study drug.
- •Participant has clinically serious cardiovascular/cerebrovascular diseases (eg, cerebrovascular accident/stroke [less than 6 month prior to enrollment], myocardial infarction [less than 6 month prior to enrollment], uncontrolled and potentially reversible cardiac conditions [unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QTcF prolongation >500 msec, electrolyte disturbances, hypertension defined as systolic >150 mmHg or diastolic >90 mmHg etc.] or participant has congenital long QT syndrome).
- •Participant has known abdominal fistula, gastrointestinal fistula or gastrointestinal perforation and/or higher risks of bleeding.
- •Participant has either myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or has features suggestive of MDS/AML.
- •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 prior to the first dose of study drug.
- •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 prior to the first dose of study drug.
- •Participant is either unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption (eg, gastrectomy, partial bowel obstruction, malabsorption).
- •Participant has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- •Participant is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 210 days after the last dose of study treatment.
- •Participant has had an allogenic tissue/solid organ transplant.
- •Participant has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the investigators.
研究组 & 干预措施
pembrolizumab and bevacizumab with PBC followed by pembrolizumab, bevacizumab and olaparib
Participants will continue treatment period up to 6 cycles and enter maintenance period after treatment period. Study treatment will be continued until progressive disease (PD) based on RECIST 1.1, death, unacceptable toxicity, or participant withdrawal from the study.
干预措施: pembrolizumab (Biological)
pembrolizumab and bevacizumab with PBC followed by pembrolizumab, bevacizumab and olaparib
Participants will continue treatment period up to 6 cycles and enter maintenance period after treatment period. Study treatment will be continued until progressive disease (PD) based on RECIST 1.1, death, unacceptable toxicity, or participant withdrawal from the study.
干预措施: olaparib (Drug)
pembrolizumab and bevacizumab with PBC followed by pembrolizumab, bevacizumab and olaparib
Participants will continue treatment period up to 6 cycles and enter maintenance period after treatment period. Study treatment will be continued until progressive disease (PD) based on RECIST 1.1, death, unacceptable toxicity, or participant withdrawal from the study.
干预措施: bevacizumab (Biological)
pembrolizumab and bevacizumab with PBC followed by pembrolizumab, bevacizumab and olaparib
Participants will continue treatment period up to 6 cycles and enter maintenance period after treatment period. Study treatment will be continued until progressive disease (PD) based on RECIST 1.1, death, unacceptable toxicity, or participant withdrawal from the study.
干预措施: carboplatin (Drug)
pembrolizumab and bevacizumab with PBC followed by pembrolizumab, bevacizumab and olaparib
Participants will continue treatment period up to 6 cycles and enter maintenance period after treatment period. Study treatment will be continued until progressive disease (PD) based on RECIST 1.1, death, unacceptable toxicity, or participant withdrawal from the study.
干预措施: paclitaxel (Drug)
pembrolizumab and bevacizumab with PBC followed by pembrolizumab, bevacizumab and olaparib
Participants will continue treatment period up to 6 cycles and enter maintenance period after treatment period. Study treatment will be continued until progressive disease (PD) based on RECIST 1.1, death, unacceptable toxicity, or participant withdrawal from the study.
干预措施: docetaxel (Drug)
结局指标
主要结局
Two-year progression-free survival rate
时间窗: 2 years
Two-year progression-free survival rate after administration of pembrolizumab and bevacizumab in combination with PBC followed by pembrolizumab, bevacizumab and olaparib as a maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer based on RECIST 1.1.
次要结局
- Overall Survival (OS)(3 years)
- Progression-Free Survival (PFS)(3 years)
- Disease Control Rate (DCR)(3 years)
- One-year progression-free survival rate(1 year)
- Incidence of adverse events(3 years)
- PFS in maintenance period by chemotherapy responder(3 years)
- Objective Response Rate (ORR)(3 years)
- Duration of Response (DOR)(3 years)
研究者
Kosei Hasegawa, MD, PhD
Professor and Director, Department of Gynecologic Oncology
Saitama Medical University International Medical Center