A Phase III, Randomized, Open Label, Multicenter, Controlled Trial of Niraparib Versus Physician's Choice in Previously-treated, HER2 Negative, Germline BRCA Mutation-positive Breast Cancer Patients
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- Tesaro, Inc.
- 入组人数
- 216
- 试验地点
- 1
- 主要终点
- Progression Free Survival (PFS) - Central Review Assessment
研究概览
简要总结
The purpose of this study is to compare progression-free survival (PFS) in patients with advanced/metastatic breast cancer who have a BRCA mutation when treated with niraparib as compared to those treated with physician's choice
详细描述
This is a phase III, randomized, open label, multicenter, controlled trial of niraparib versus physician's choice in previously-treated, HER2 negative, germline BRCA mutation-positive breast cancer patients. Niraparib is an orally active PARP inhibitor. Niraparib (in a 2:1 ratio) will be administered once daily continuously during a 21-day cycle. Physician's choice will be administered on a 21-day cycle. Health-related quality of life will be measured. The safety and tolerability will be assessed by clinical review of adverse events (AEs), physical examinations, electrocardiograms (ECGs), and safety laboratory values.
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
- All
- 接受健康志愿者
- 否
入选标准
- •Germline BRCA1 or BRCA2 mutation; patients with unknown BRCA status who meet NCCN BRCA screening criteria will be screened for BRCA mutation.
- •Histologically or cytologically confirmed HER2-negative metastatic or locally advanced disease that is not amenable to resection or radiation with curative intent.
- •Up to 2 prior cytotoxic regimens for advanced or metastatic breast cancer; patients with no prior cytotoxic regimens for advanced or metastatic disease will only be allowed if they relapsed during or within 12 months of (neo-) adjuvant cytotoxic therapy.
- •Prior therapy should have included a taxane and/or anthracycline (unless contraindication to those) in the neoadjuvant, adjuvant, or advanced/metastatic setting.
- •a. Hormone receptor positive patients must also have hormone resistant disease; either relapsed while on adjuvant endocrine treatment, or within one year of completing adjuvant endocrine treatment, or progression on at least one line of endocrine treatment for advanced cancer.
- •ECOG performance status 0-2
- •Adequate bone marrow, kidney and liver function
排除标准
- •Patients with platinum resistant cancer
- •Symptomatic uncontrolled brain metastases
- •Prior diagnosis of Stage IV ovarian cancer; Stage III ovarian cancer must have a 5-year disease-free interval; Stage II ovarian cancer must have a 2-year disease-free interval
- •Known hypersensitivity to the components of niraparib
- •Invasive cancer other than breast cancer within 2 years (except basal or squamous cell carcinoma of the skin that has been definitely treated)
- •Pregnant or breast feeding patients
- •Immunocompromised patients
- •Known active Hepatitis B or C
- •Prior treatment with a PARP inhibitor
- •Known history of myelodysplastic syndrome (MDS).
- •known and persistent (>4 weeks) >/= grade 3 toxicity or fatigue from prior cancer treatment.
研究组 & 干预措施
Physician's choice
Physician may select from 4 active comparators
干预措施: Physician's choice (Drug)
niraparib
Patients will be randomized 2:1 to receive niraparib 300 mg (3x100 mg capsules) once daily for 21 continuous days
干预措施: niraparib (Drug)
结局指标
主要结局
Progression Free Survival (PFS) - Central Review Assessment
时间窗: From the date of randomization to the date of disease progression or death due to any cause, whichever occurs earlier, up to 4 years
The primary objective of this study is to compare progression-free survival (PFS), as assessed by blinded central review, of participants with advanced/metastatic human epidermal growth factor receptor 2 (HER2)-negative gBRCA mutation breast cancer when treated with niraparib as compared to those treated with physician's choice single agent chemotherapy standards (eribulin, vinorelbine, gemcitabine or capecitabine). PFS is defined as the date of randomization to the date of disease progression or death due to any cause, whichever occurs earlier as per Response evaluation criteria in solid tumors (RECIST) version (v)1.1 as determined by central review assessment. Progressive Disease is defined as at least a 20 percent (%) increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded on study (including Baseline) and an absolute increase of \>= 5 millimeter (mm).
次要结局
- Overall Survival(From treatment randomization to date of death of any cause, up to 4 years)
- Number of Participants With Central BRCA Mutation Status(At Baseline (Cycle 1 Day1) (Cycle duration was 21 days))
- Number of Participants With Serious Adverse Events (SAE) and Non-serious Adverse Events (Non-SAE)(Up to 7 years)
- Progression Free Survival (PFS) - Investigator Assessment(Assessed up to 4 years)
- Time to Treatment Failure(Date of randomization to discontinuation of treatment for any reason, up to 4 years)
- Overall Response Rate (ORR)(Up to 4 years)
- Duration of Response (DOR)(Up to 4 years)
- Number of Participants With Serious Adverse Events Related to New Malignancy(Up to 7 years)
- Number of Participants With Subsequent Anticancer Therapies(Up to 7 years)