A Randomized, Phase 2 Study of the Efficacy and Tolerability of Veliparib in Combination With Temozolomide or Veliparib in Combination With Carboplatin and Paclitaxel Versus Placebo Plus Carboplatin and Paclitaxel in Subjects With BRCA1 or BRCA2 Mutation and Metastatic Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 294
- 试验地点
- 120
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
The primary objective of the study is to assess the progression-free survival (PFS) of oral veliparib in combination with TMZ or in combination with carboplatin and paclitaxel compared to placebo plus carboplatin and paclitaxel in subjects with BRCA1 or BRCA2 mutation and locally recurrent or metastatic breast cancer.
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
- Double (Participant, Investigator)
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 breast cancer that is either locally recurrent or metastatic.
- •Locally recurrent disease must not be amenable to surgical resection or radiation with curative intent.
- •Must have a documented deleterious Breast Cancer Gene BRCA1 or BRCA2 germline mutation.
- •If Human Epidermal Growth Factor Receptor (HER2) positive, subjects must have received and progressed on at least one prior standard HER2 directed therapy or the subject must be ineligible to receive anti-HER2 therapy.
- •Measurable or non-measurable (but radiologically evaluable) disease by RECIST (Response Evaluation Criteria in Solid Tumors) criteria 1.
- •Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-
- •Subject must have adequate bone marrow, renal and hepatic function.
- •Subject must not be pregnant or plan to conceive a child.
排除标准
- •Received anticancer agent(s) or an investigational agent within 21 days prior to C1D1, or radiotherapy within 28 days prior Cycle 1 Day
- •More than 2 prior lines of cytotoxic chemotherapy.
- •Prior treatment of breast cancer with temozolomide, a platinum agent, or a Poly (ADP ribose) Polymerase (PARP) inhibitor.
- •Prior taxane therapy for metastatic breast cancer.
- •A history of or evidence of brain metastases or leptomeningeal disease.
- •A history of uncontrolled seizure disorder.
- •Pre-existing neuropathy from any cause in excess of Grade
- •Known history of allergic reaction to cremophor/paclitaxel.
- •Clinical significant uncontrolled conditions, active infection, myocardial infarction, stroke, or transient ischemic attack, psychiatric illness/social situations that would limit compliance.
- •Pregnant or breastfeeding.
研究组 & 干预措施
Veliparib with Temozolomide
Veliparib 40 mg twice daily (BID) Days 1 through 7 plus TMZ 150 to 200 mg/m^2 QD Days 1 through 5 in each 28-day cycle.
干预措施: Veliparib (Drug)
Veliparib with Temozolomide
Veliparib 40 mg twice daily (BID) Days 1 through 7 plus TMZ 150 to 200 mg/m^2 QD Days 1 through 5 in each 28-day cycle.
干预措施: Temozolomide (Drug)
Placebo with Carboplatin and Paclitaxel
Placebo BID Days 1 through 7 plus carboplatin target area under the curve (mg•min/mL) (AUC) 6 administered on Day 3 of each 21-day cycle and paclitaxel 175 mg/m^2 administered on Day 3 of each 21-day cycle.
干预措施: Placebo (Drug)
Placebo with Carboplatin and Paclitaxel
Placebo BID Days 1 through 7 plus carboplatin target area under the curve (mg•min/mL) (AUC) 6 administered on Day 3 of each 21-day cycle and paclitaxel 175 mg/m^2 administered on Day 3 of each 21-day cycle.
干预措施: Carboplatin (Drug)
Placebo with Carboplatin and Paclitaxel
Placebo BID Days 1 through 7 plus carboplatin target area under the curve (mg•min/mL) (AUC) 6 administered on Day 3 of each 21-day cycle and paclitaxel 175 mg/m^2 administered on Day 3 of each 21-day cycle.
干预措施: Paclitaxel (Drug)
Veliparib with Carboplatin and Paclitaxel
Veliparib 80 mg BID Days 1 through 7 plus carboplatin target AUC 6 administered on Day 3 of each 21-day cycle and paclitaxel 175 mg/m^2 administered on Day 3 of each 21-day cycle.
干预措施: Veliparib (Drug)
Veliparib with Carboplatin and Paclitaxel
Veliparib 80 mg BID Days 1 through 7 plus carboplatin target AUC 6 administered on Day 3 of each 21-day cycle and paclitaxel 175 mg/m^2 administered on Day 3 of each 21-day cycle.
干预措施: Carboplatin (Drug)
Veliparib with Carboplatin and Paclitaxel
Veliparib 80 mg BID Days 1 through 7 plus carboplatin target AUC 6 administered on Day 3 of each 21-day cycle and paclitaxel 175 mg/m^2 administered on Day 3 of each 21-day cycle.
干预措施: Paclitaxel (Drug)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: Radiographic evaluation every 9 weeks, clinical evaluation every cycle (data cutoff date: 04 March 2016); maximum duration of follow up for PFS was 34 months.
PFS is defined as the number of months from the date the participant was randomized to the date of radiographic progression as determined by the central imaging center, or to the date of all cause deaths within 63 days of last tumor assessment if disease progression was not reached.
次要结局
- Overall Survival (OS)(From Cycle 1 Day 1 until participant's death or 3 years post discontinuation (data cutoff date: 04 March 2016); maximum duration of follow up for OS was 72 months.)
- Clinical Benefit Rate (CBR) at Week 18(Week 18)
- Objective Response Rate (ORR)(Radiographic evaluation every 9 weeks, clinical evaluation every cycle (data cutoff date: 04 March 2016); maximum duration of follow up for ORR was 34 months.)
- Change From Baseline at Week 18 in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy Module (EORTC QLQ-CIPN20) Sensory Subscale Score(Baseline, Week 18)