NCT01945775已完成3 期
A PHASE 3, OPEN-LABEL, RANDOMIZED PARALLEL,2-ARM,MULTI-CENTER STUDY OF TALAZOPARIB(BMN 673) VERSUS PHYSICIAN'S CHOICE IN GERMLINE BRCA MUTATION SUBJECTS WITH LOCALLY ADVANCED AND/OR METASTATIC BREAST CANCER, WHO HAVE RECEIVED PRIOR CHEMOTHERAPY REGIMENS FOR METASTATIC DISEASE
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 431
- 试验地点
- 270
- 主要终点
- Progression-Free Survival (PFS): Independent Radiological Facility (IRF) Assessment
研究概览
简要总结
The purpose of this open-label, 2:1 randomized phase III trial is to compare the safety and efficacy of talazoparib (also known as BMN 673) versus protocol-specific physician's choice in patients who have locally advanced and/or metastatic breast cancer with germline BRCA mutations.
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
- •Histologically or cytologically confirmed carcinoma of the breast
- •Locally advanced breast cancer that is not amenable to curative radiation or surgical cure and/or metastatic disease appropriate for systemic single cytotoxic chemotherapy
- •Documentation of a deleterious, suspected deleterious, or pathogenic germline BRCA1 or BRCA2 mutation from Myriad Genetics or other laboratory approved by the Sponsor
- •No more than 3 prior chemotherapy-inclusive regimens for locally advanced and/or metastatic disease (no limit on prior hormonal therapies or targeted anticancer therapies such as mechanistic target of rapamycin (mTOR) or CDK4/6 inhibitors, immune-oncology agents, tyrosine kinase inhibitors, or monoclonal antibodies against CTL4 or VEGF)
- •Prior treatment with a taxane and/or anthracycline in the neoadjuvant, adjuvant, locally advanced, or metastatic setting unless medically contraindicated
- •Have measurable or non-measurable, evaluable disease by the revised response evaluation criteria in solid tumors (RECIST) v.1.1
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
排除标准
- •First-line locally advanced and/or metastatic breast cancer with no prior adjuvant chemotherapy unless the Investigator determines that one of the 4 cytotoxic chemotherapy agents in the control arm would otherwise be offered to the subject
- •Prior treatment with a PARP inhibitor (not including iniparib)
- •Not a candidate for treatment with at least 1 of the treatments of protocol-specific physician's choice (ie, capecitabine, eribulin, gemcitabine, vinorelbine)
- •Subjects who had objective disease progression while receiving platinum chemotherapy administered for locally advanced or metastatic disease; subjects who received low-dose platinum therapy administered in combination with radiation therapy are not excluded
- •Subjects who have received platinum in the adjuvant or neoadjuvant setting are eligible; however, subjects may not have relapsed within 6 months of the last dose of prior platinum therapy
- •Cytotoxic chemotherapy within 14 days before randomization
- •Radiation or anti-hormonal therapy or other targeted anticancer therapy within 14 days before randomization
- •HER2 positive breast cancer
- •Active inflammatory breast cancer
- •CNS metastases
- •Exception: Adequately treated brain metastases documented by baseline CT or MRI scan that has not progressed since previous scans and that does not require corticosteroids (except prednisone ≤ 5 mg/day or equivalent) for management of CNS symptoms. A repeat CT or MRI following the identification of CNS metastases (obtained at least 2 weeks after definitive therapy) must document adequately treated brain metastases.
- •Subjects with leptomeningeal carcinomatosis are not permitted
- •Prior malignancy except for any of the following:
- •Prior BRCA-associated cancer as long as there is no current evidence of the cancer
- •Carcinoma in situ or non-melanoma skin cancer
- •A cancer diagnosed and definitively treated ≥ 5 years before randomization with no subsequent evidence of recurrence
- •Known to be human immunodeficiency virus positive
- •Known active hepatitis C virus, or known active hepatitis B virus
- •Known hypersensitivity to any of the components of talazoparib
研究组 & 干预措施
talazoparib
Experimental
Patient will be randomized 2:1 to receive talazoparib oral capsules (1.0 mg) once daily for 21 continuous days
干预措施: talazoparib (Drug)
Physician's-Choice
Active Comparator
Capecitabine, Eribulin, Gemcitabine or Vinorelbine
干预措施: Physician's-Choice (Drug)
结局指标
主要结局
Progression-Free Survival (PFS): Independent Radiological Facility (IRF) Assessment
时间窗: Baseline until radiologic progressive disease or death due to any cause (up to maximum duration of 36.9 months)
IRF assessed PFS was defined as time (in months) from randomization until the date of first documented radiologic progressive disease per response evaluation criteria in solid tumors (RECIST) version 1.1 or death from any cause, whichever occurs first. As per RECIST v1.1, progression defined as 1) for target lesions: at least a 20% increase in the sum of target lesion measurements, compared to the smallest sum on study (including baseline), the absolute increase in the sum has to be at least 5 millimeter (mm); 2) for non-target lesions: unequivocal progression of non-target lesions, evaluated as a whole, such that it is clear that treatment has failed and disease is progressing, regardless of the status of the target lesions; 3) and/or appearance of one or more new lesions. The analysis was performed by Kaplan-Meier method.
次要结局
- Overall Survival (OS)(Baseline until death due to any cause or analysis cut-off, up to a maximum duration of 61.4 months)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)(Talazoparib: Baseline up to a maximum duration of 71.3 months; Physician's Choice Treatment: Baseline up to maximum duration of 46.1 months)
- Number of Participants Taking At-least One Concomitant Medication(Talazoparib: Baseline up to a maximum duration of 71.3 months; Physician's Choice Treatment: Baseline up to maximum duration of 46.1 months)
- Percentage of Participants With Objective Response: Investigator Assessment(Baseline until radiologic progressive disease or death due to any cause (up to a maximum duration of 36.9 months))
- Number of Participants With Grade 3 or 4 Post-baseline Toxicities in Laboratory Parameters: Hematology(Talazoparib: Baseline up to a maximum duration of 71.3 months; Physician's Choice Treatment: Baseline up to maximum duration of 46.1 months.)
- Number of Participants With Grade 3 or 4 Post-baseline Toxicities in Laboratory Parameters: Chemistry(Talazoparib: Baseline up to a maximum duration of 71.3 months; Physician's Choice Treatment: Baseline up to maximum duration of 46.1 months)
- Number of Participants With Potentially Clinically Significant Changes From Baseline in Vital Signs(Talazoparib: Baseline up to a maximum duration of 71.3 months; Physician's Choice Treatment: Baseline up to maximum duration of 46.1 months)
- Trough Plasma Talazoparib Concentrations(Predose on Day 1 of Cycle 2, 3 and 4)
研究者
研究点 (270)
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