TRITON3: A Multicenter, Randomized, Open Label Phase 3 Study of Rucaparib Versus Physician's Choice of Therapy for Patients With Metastatic Castration Resistant Prostate Cancer Associated With Homologous Recombination Deficiency
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 405
- 试验地点
- 149
- 主要终点
- Radiographic Progression-free Survival (rPFS) by IRR in Participants With a BRCA or ATM Alteration Combined
研究概览
简要总结
The purpose of this study is to determine how participants with metastatic castration-resistant prostate cancer, and evidence of a homologous recombination gene deficiency, respond to treatment with rucaparib versus treatment with physician's choice of abiraterone acetate, enzalutamide, or docetaxel.
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
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Be 18 years old at the time the informed consent is signed
- •Have a histologically or cytologically confirmed adenocarcinoma or poorly differentiated carcinoma of the prostate that is metastatic
- •Be surgically or medically castrated, with serum testosterone levels of ≤ 50 ng/dL (1.73 nM)
- •Be eligible for treatment with physician's choice of comparator treatment (abiraterone acetate, enzalutamide or docetaxel)
- •Experienced disease progression after having received 1 prior next generation androgen receptor-targeted therapy
- •Have a deleterious mutation in a BRCA1/2 or ATM gene
排除标准
- •Active second malignancy, with the exception of curatively treated non melanoma skin cancer, carcinoma in situ, or superficial bladder cancer
- •Prior treatment with any PARP inhibitor
- •Prior treatment with chemotherapy for metastatic castration-resistant prostate cancer
- •Symptomatic and/or untreated central nervous system metastases
- •Pre-existing duodenal stent and/or any gastrointestinal disorder or defect that would, in the opinion of the investigator, interfere with absorption of study drug
研究组 & 干预措施
Rucaparib
Oral rucaparib (monotherapy).
干预措施: Rucaparib (Drug)
Abiraterone acetate or Enzalutamide or Docetaxel
Oral abiraterone acetate (monotherapy, given in combination with prednisone). Oral enzalutamide (monotherapy). Intravenous docetaxel (monotherapy, given in combination with prednisone or prednisolone).
干预措施: Abiraterone acetate or Enzalutamide or Docetaxel (Drug)
结局指标
主要结局
Radiographic Progression-free Survival (rPFS) by IRR in Participants With a BRCA or ATM Alteration Combined
时间窗: From enrollment to primary completion of study (Total follow-up was up to approximately 4 years)
The primary efficacy endpoint for the study is rPFSirr, defined as the time from randomization to the first objective evidence of radiographic progression, or death due to any cause (whichever occurs first). Radiographic disease progression includes confirmed soft tissue disease progression and confirmed bone disease progression as per modified RECIST Version 1.1 (at least a 20% increase in the sum of the LD of target lesions or appearance of one or more new extra-skeletal lesions and/or unequivocal progression of existing nontarget lesions) or PCWG3 criteria (Progression by bone is determined by PCWG3 criteria in which at least two new lesions appearing during the first 12-week flare window followed by 2 additional new lesions in the confirmatory scan appearing after the 12-week flare window, or after the 12-week flare window, at least 2 new lesions relative to the first post-treatment scan confirmed on a subsequent scan).
Radiographic Progression-free Survival (rPFS) by IRR in Participants With a BRCA Alteration
时间窗: From enrollment to primary completion of study (Total follow-up was up to approximately 4 years)
The primary efficacy endpoint for the study is rPFSirr, defined as the time from randomization to the first objective evidence of radiographic progression, or death due to any cause (whichever occurs first). Radiographic disease progression includes confirmed soft tissue disease progression and confirmed bone disease progression as per modified RECIST Version 1.1 (at least a 20% increase in the sum of the LD of target lesions or appearance of one or more new extra-skeletal lesions and/or unequivocal progression of existing nontarget lesions) or PCWG3 criteria Progression by bone is determined by PCWG3 criteria in which at least two new lesions appearing during the first 12-week flare window followed by 2 additional new lesions in the confirmatory scan appearing after the 12-week flare window, or after the 12-week flare window, at least 2 new lesions relative to the first post-treatment scan confirmed on a subsequent scan).
次要结局
- Overall Survival in Participants With a BRCA Alteration(From enrollment to completion of study (up to approximately 7 years))
- Objective Response Rate (ORR) by IRR in Participants With a BRCA or ATM Alteration Combined(From enrollment to primary completion of study (Total follow-up was up to approximately 4 years))
- Duration of Response (DOR) by IRR in Participants With a BRCA Alteration(From enrollment to primary completion of study (Total follow-up was up to approximately 4 years))
- PSA Response in Participants With a BRCA or ATM Alteration Combined(From enrollment to primary completion of study (up to approximately 5 years))
- Overall Survival in Participants With a BRCA or ATM Alteration Combined(From enrollment to completion of study (up to approximately 7 years))
- Objective Response Rate (ORR) by IRR in Participants With a BRCA Alteration(From enrollment to primary completion of study (Total follow-up was up to approximately 4 years))
- Duration of Response (DOR) by IRR in Participants With a BRCA or ATM Alteration Combined(From enrollment to primary completion of study (Total follow-up was up to approximately 4 years))
- PSA Response in Participants With a BRCA Alteration(From enrollment to primary completion of study (up to approximately 5 years))
- Clinical Benefit Rate (CBR) by IRR at 6 Months in Participants With a BRCA Alteration(From enrollment to 6 months)
- Time to Prostate Specific Antigen (PSA) Progression in Participants With a BRCA or ATM Alteration Combined(From enrollment to primary completion of study (up to approximately 5 years))
- Change in Patient-reported Outcome (PRO) in Participants With a BRCA Alteration: FACT-P(From enrollment to up to approximately 25 weeks)
- Change in Patient-reported Outcome (PRO) in Participants With a BRCA Alteration: BPI-SF(From enrollment to up to approximately 25 weeks)
- Change in Patient-reported Outcome (PRO) in Participants With a BRCA Alteration: EQ-5D-5L(From enrollment to up to approximately 25 weeks)
- Trough Plasma PK (Cmin) of Rucaparib Based on Sparse Sampling(From enrollment to week 5 of dosing)
- Clinical Benefit Rate (CBR) by IRR at 6 Months in Participants With a BRCA or ATM Alteration Combined(From enrollment to 6 months)
- Time to Prostate Specific Antigen (PSA) Progression in Participants With a BRCA Alteration(From enrollment to primary completion of study (up to approximately 5 years))