A Phase 3 Randomized Double-blind Trial of Maintenance With Niraparib Versus Placebo in Patients With Platinum Sensitive Ovarian Cancer.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Tesaro, Inc.
- 入组人数
- 596
- 试验地点
- 1
- 主要终点
- Progression-Free Survival (PFS) in Cohort With Germline BReast CAncer Gene (BRCA) Mutation (gBRCA)
研究概览
简要总结
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study of niraparib as maintenance in platinum sensitive ovarian cancer patients who have either gBRCAmut or a tumor with high-grade serous histology and who have responded to their most recent chemotherapy containing a platinum agent. Niraparib is an orally active PARP inhibitor. Niraparib or placebo (in a 2:1 ratio) will be administered once daily continuously during a 28-day cycle. Health-related quality of life will be measured by the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI), European Quality of Life scale, 5-Dimensions (EQ-5D), and a neuropathy questionnaire. Safety and tolerability will be assessed by clinical review of adverse events (AEs), physical examinations, electrocardiograms (ECGs), and safety laboratory values.
The primary objective of this study is to evaluate efficacy of niraparib as maintenance therapy in patients who have platinum sensitive ovarian cancer as assessed by the prolongation of progression free survival (PFS).
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 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •18 years of age or older, female, any race
- •Histologically diagnosed ovarian cancer, fallopian tube cancer or primary peritoneal cancer
- •High grade (or grade 3) serous histology or known to have gBRCAmut
- •Has received at least 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 month period between penultimate platinum regimen and progression of disease)
- •Has responded to last the platinum regimen, remains in response and is enrolled on study within 8 weeks of completion of the last platinum regimen
- •Adequate bone marrow, kidney and liver function
排除标准
- •Known hypersensitivity to the components of niraparib
- •Invasive cancer other than ovarian cancer within 2 years (except basal or squamous cell carcinoma of the skin that has been definitely treated)
- •Symptomatic uncontrolled brain metastasis
- •Is pregnant or breast feeding
- •Immunocompromised patients
- •Known active hepatic disease
- •Prior treatment with a known PARP inhibitor
研究组 & 干预措施
Placebo
Administered once daily continuously over a 28 day cycle.
干预措施: placebo (Drug)
结局指标
主要结局
Progression-Free Survival (PFS) in Cohort With Germline BReast CAncer Gene (BRCA) Mutation (gBRCA)
时间窗: From date of randomization to the earliest date of disease progression or death from any cause, up to 7 years 7 months and 4 days
PFS was defined as the time between randomization and disease progression or death from any cause. Computed tomography or magnetic resonance imaging to assess disease progression was performed at baseline, every 8 weeks through cycle 14, and then every 12 weeks until treatment discontinuation. The objective assessment of disease progression was determined by means of central radiologic and clinical review, according to Response Evaluation Criteria in Solid Tumors (RECIST),version 1.1, which was performed in a blinded fashion. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study.
Progression-Free Survival (PFS) in Cohort With No Germline BCRA With Homologous Recombination Deficiency-positive (HRD+) Tumors (Non-gBRCAmut HRD+)
时间窗: From date of randomization to the earliest date of disease progression or death from any cause, up to 7 years, 7 months and 4 days
PFS was defined as the time between randomization and disease progression or death from any cause. Computed tomography or magnetic resonance imaging to assess disease progression was performed at baseline, every 8 weeks through cycle 14, and then every 12 weeks until treatment discontinuation. The objective assessment of disease progression was determined by means of central radiologic and clinical review, according to Response Evaluation Criteria in Solid Tumors (RECIST),version 1.1, which was performed in a blinded fashion. PD was defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study.
Progression-Free Survival (PFS) in Cohort With No Germline BRCA Mutation
时间窗: From date of randomization to the earliest date of disease progression or death from any cause, up to 7 years, 7 months and 4 days
PFS was defined as the time between randomization and disease progression or death from any cause. Computed tomography or magnetic resonance imaging to assess disease progression was performed at baseline, every 8 weeks through cycle 14, and then every 12 weeks until treatment discontinuation. The objective assessment of disease progression was determined by means of central radiologic and clinical review, according to Response Evaluation Criteria in Solid Tumors (RECIST),version 1.1, which was performed in a blinded fashion.PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study.
次要结局
- Time to First Subsequent Therapy in Cohort With Germline BRCA Mutation (gBRCA)(From date of randomization to the earliest date of first subsequent therapy or death, up to 7 years, 7 months and 4 days)
- Time to First Subsequent Therapy in Cohort With No Germline BRCA Mutation(From date of randomization to the earliest date of first subsequent therapy or death, up to 7 years, 7 months and 4 days)
- Progression-Free Survival 2 in Cohort With Germline BRCA Mutation (gBRCA)(From treatment randomization to the earlier of the date of disease progression on the next anti-cancer therapy following study treatment or death due to any cause, up to 7 years, 7 months and 4 days)
- Chemotherapy-Free Interval in Cohort With Germline BRCA Mutation (gBRCA)(From date of last platinum therapy prior to randomization to the initiation of the next anti-cancer therapy after maintenance treatment, up to 7 years, 7 months and 4 days)
- Chemotherapy-Free Interval in Cohort With No Germline BRCA Mutation(From date of last platinum therapy prior to randomization to the initiation of the next anti-cancer therapy after maintenance treatment, up to 7 years, 7 months and 4 days)
- Progression-Free Survival 2 in Cohort With No Germline BRCA Mutation(From treatment randomization to the earlier of the date of disease progression on the next anti-cancer therapy following study treatment or death due to any cause, up to 7 years, 7 months and 4 days)
- Overall Survival in Cohort With Germline BRCA Mutation (gBRCA)(From treatment randomization to date of death by any cause, up to 7 years, 7 months and 4 days)
- Overall Survival in Cohort With No Germline BRCA Mutation(From treatment randomization to date of death by any cause, up to 7 years, 7 months and 4 days)
- Time to Second Subsequent Therapy in Cohort With Germline BRCA Mutation (gBRCA)(From the date of randomization to the start date of the second subsequent anti-cancer therapy, up to 7 years, 7 months and 4 days)
- Time to Second Subsequent Therapy in Cohort With No Germline BRCA Mutation(From the date of randomization to the start date of the second subsequent anti-cancer therapy, up to 7 years, 7 months and 4 days)
- Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at Cycle 2(Baseline (pre-dose on Day 1) and at Cycle 2 (Each cycle was of 28 days))
- Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 6(At Cycle 6 (Each cycle was of 28 days))
- Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 6(At Cycle 6 (Each cycle was of 28 days))
- Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at Cycle 4(Baseline (Pre-dose on Day 1) and at Cycle 4 (Each cycle was of 28 days))
- Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at Cycle 6(Baseline (pre-dose on Day 1) and at Cycle 6 (Each cycle was of 28 days))
- Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at Post-progression(Baseline (Pre-dose on Cycle 1 Day 1, Each cycle was of 28 days) and up to 7 years, 7 months and 4 days)
- Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at Cycle 2(Baseline (Pre-dose on Day 1) and at Cycle 2 (Each cycle was of 28 days))
- Change From Baseline in EQ-5D-5L in Cohort With Germline BRCA at Post-progression(Baseline (Pre-dose on Day 1) and up to 7 years, 7 months and 4 days)
- Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 4(At Cycle 4 (Each cycle was of 28 days))
- Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at Cycle 4(Baseline (Pre-dose on Day 1) and at Cycle 4 (Each cycle was of 28 days))
- Change From Baseline in EQ-5D-5L in Cohort With Germline BRCA at Cycle 4(Baseline (Pre-dose on Day 1) and at Cycle 4 (Each cycle was of 28 days))
- Change From Baseline in EQ-5D-5L in Cohort With Germline BRCA at Cycle 6(Baseline (Pre-dose on Day 1) and at Cycle 6 (Each cycle was of 28 days))
- Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at Cycle 6(Baseline (Pre-dose on Day 1) and at Cycle 6 (Each cycle was of 28 days))
- Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at Post-progression(Baseline (Pre-dose on Day 1) and up to 7 years, 7 months and 4 days)
- Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at Cycle 6(Baseline (Pre-dose on Day 1) and at Cycle 6 (Each cycle was of 28 days))
- Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Baseline(At Baseline)
- Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 2(At Cycle 2 (Each cycle was of 28 days))
- Change From Baseline in European Quality of Life Scale, 5-Dimensions (EQ-5D-5L) in Cohort With Germline BRCA at Cycle 2(Baseline (Pre-dose on Day 1) and at Cycle 2 (Each cycle was of 28 days))
- Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at Cycle 2(Baseline (Pre-dose on Day 1) and at Cycle 2 (Each cycle was of 28 days))
- Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at Cycle 4(Baseline (Pre-dose on Day 1) and at Cycle 4 (Each cycle was of 28 days))
- Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at Post-progression(Baseline (Pre-dose on Day 1) and up to 7 years, 7 months and 4 days)
- Number of Participants With Concordance of a Candidate Companion BRAC Analysis Diagnostic Test Compared to the Centralized BRCA Mutation Test Used in This Study(Up to 7 years, 7 months and 4 days)
- Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Post-progression(Up to 7 years, 7 months and 4 days)
- Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Post-progression(Up to 7 years, 7 months and 4 days)
- Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Baseline(At Baseline)
- Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 2(At Cycle 2 (Each cycle was of 28 days))
- Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 4(At Cycle 4 (Each cycle was of 28 days))
- Number of Participants With Concordance of a Candidate Companion HRD Diagnostic Test Compared to the HRD Test Used in This Study(Up to 7 years, 7 months and 4 days)
- Number of Participants With Non-serious Adverse Events (AEs) and Serious AEs (SAEs)(Up to 7 years, 7 months and 6 days)
- Number of Participants With Non-serious AEs and SAEs (Post-study Unblinding)(Up to 8 months, 26 days)
- Number of Participants With Non-serious AEs and SAEs in FE Sub-study(Up to 2 years, 3 months and 11 days)
- Number of Participants With Non-serious AEs and SAEs in QTc Sub-study(Up to 5 years 10 months and 22 days)
- Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC[0-infinity]) Following Administration of Niraparib (FE Sub-study)(Pre-dose and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post dose)
- Area Under the Plasma Concentration-time Curve From Time 0 to the Last Quantifiable Concentration (AUC[0-last]) Following Administration of Niraparib (FE Sub-study)(Pre-dose (Day -1) and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post dose)
- Maximum Observed Plasma Concentration (Cmax) Following Administration of Niraparib (FE Sub-study)(Pre-dose (Day -1) and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post dose)
- Time to Reach Maximum (Tmax) Following Administration of Niraparib (FE Sub-study)(Pre-dose (Day -1) and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post dose)
- Terminal Elimination Half-life (t1/2) Following Administration of Niraparib (FE Sub-study)(Pre-dose (Day -1) and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post dose)
- Number of Participants With Maximum Post-Baseline QT Interval Corrected by Fridericia's Formula (QTcF) Greater Than Pre-specified Thresholds(At Baseline (Cycle 1 Day 1, each cycle was of 28 days))