A Phase III, Randomised, Double Blind, Placebo Controlled, Multicentre Study of Maintenance Olaparib Monotherapy in Patients With gBRCA Mutated Metastatic Pancreatic Cancer Whose Disease Has Not Progressed on First Line Platinum Based Chemotherapy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 154
- 试验地点
- 1
- 主要终点
- Progression-free Survival (PFS) by Blinded Independent Central Review (BICR) Using Modified Response Evaluation Criteria in Solid Tumours. This Study Used Modified RECIST Version (v) 1.1 (RECIST v1.1)
研究概览
简要总结
A Phase III, Randomised, Double Blind, Placebo Controlled, Multicentre Study of Maintenance Olaparib Monotherapy in Patients with gBRCA Mutated Metastatic Pancreatic Cancer whose Disease Has Not Progressed on First Line Platinum Based Chemotherapy
详细描述
Approximately 145 patients will be randomised using an Interactive Voice Response System /Interactive Web Response System (IVR/IWR system) in a 3:2 ratio (Olaparib:placebo) to the treatments as specified below:
- Olaparib tablets p.o. 300 mg twice daily
- Matching placebo tablets p.o. twice daily Eligible patients will be those patients with pancreas cancer previously treated for metastatic disease who have not progressed following completion of at least 16 weeks (can be more) of first line platinum-based chemotherapy. All patients must have a known deleterious or suspected deleterious germline BRCA mutation to be randomised; this may have been determined prior to enrolment into the study or may be assessed as part of the enrolment procedure for the study (via centrally provided MyriadIntegrated BRAC.
Patients will be randomised within 6 weeks after their last dose of chemotherapy (last dose is the day of the last infusion) and treatment started as soon as possible but no less than 4 and no more than 8 weeks of the last chemotherapy dose. At the time of starting protocol treatment, all previous chemotherapy treatment should be discontinued.
Following randomisation, patients will attend clinic visits weekly for the first 4 weeks of treatment (Days 8, 15, 22 and 29). Patients will then attend clinic visits every 4 weeks whilst on study treatment. Patients should continue to receive study treatment until objective radiological disease progression as per RECIST as assessed by the investigator and as long as in the investigator's opinion they are benefiting from treatment and they do not meet any other discontinuation criteria.
Once a patient has progressed the patient will be followed for second progression (PFS2) every 8 weeks and then survival until the final analysis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 130 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •gBRCA1 and/or gBRCA2 mutations that are considered to be non detrimental (eg, "Variants of uncertain clinical significance" or "Variant of unknown significance" or "Variant, favour polymorphism" or "benign polymorphism" etc.)
- •Progression of tumour between start of first line platinum based chemotherapy for metastatic pancreas cancer and randomisation.
- •Cytotoxic chemotherapy or non-hormonal targeted therapy within 28 days of Cycle
- •1 Day 1 is not permitted.
- •Exposure to an investigational product within 30 days or 5 half lives (whichever is longer) prior to randomisation
- •Any previous treatment with a PARP inhibitor, including Olaparib
研究组 & 干预措施
Olaparib
Olaparib tablets po. 300 mg twice daily
干预措施: Olaparib (Drug)
Placebo
Placebo tablets twice daily
干预措施: Placebo (Drug)
结局指标
主要结局
Progression-free Survival (PFS) by Blinded Independent Central Review (BICR) Using Modified Response Evaluation Criteria in Solid Tumours. This Study Used Modified RECIST Version (v) 1.1 (RECIST v1.1)
时间窗: Up to 4 years
To determine the efficacy of olaparib maintenance monotherapy compared to placebo by PFS. The PFS was defined as the time from randomisation until the date of objective radiological disease progression according to modified RECIST v1.1 or death (by any cause in the absence of disease progression) regardless of whether the patient withdrew from randomized therapy or received another anticancer therapy prior to disease progression.
次要结局
- Time From Randomisation to Second Progression (PFS2)(Up to 4 years)
- Time From Randomisation to First Subsequent Therapy or Death (TFST)(Up to 4 years)
- Adjusted Mean Change From Baseline up to 6 Months in Global Quality of Life (QoL) Score From the EORTC-QLQ-C30 Questionnaire(From baseline up to 6 months)
- Time From Randomisation to Study Treatment Discontinuation or Death (TDT)(Up to 4 years)
- Number of Participants With Objective Response Rate (ORR) by BICR Using Modified RECIST 1.1(Up to 4 years)
- Disease Control Rate (DCR) by BICR Using Modified RECIST 1.1(At 16 weeks)
- Overall Survival (OS)(Upto 4 years)
- Time From Randomisation to Second Subsequent Therapy or Death (TSST)(Up to 4 years)
- Number of Participants With Adverse Events (AEs)(Up to 4 years)