A Phase 1 Study of ABT-888 in Combination With Carboplatin and Paclitaxel in Advanced Solid Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 107
- 试验地点
- 7
- 主要终点
- Recommended phase II dose (RP2D) for each stratum
研究概览
简要总结
This phase I trial is studying the side effects and best dose of veliparib when given together with carboplatin and paclitaxel in treating patients with advanced solid cancer. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving veliparib together with carboplatin and paclitaxel may help kill more tumor cells.
详细描述
PRIMARY OBJECTIVES:
I. To determine the recommended dose for phase II studies of veliparib (ABT-888 ) that can be administered in combination with carboplatin and paclitaxel in patients with advanced solid malignancies. (Stratum I) II. To determine the recommended dose for phase II studies of veliparib that can be administered in combination with carboplatin and paclitaxel in patients with advanced solid malignancies that harbor a germline BRCA1/2 mutation. (Stratum II) (added 04/07/09)
SECONDARY OBJECTIVES:
I. To define the dose-limiting toxicity and other toxicities associated with the use of this combination.
II. To obtain preliminary evidence of antitumor activity in patients treated with this combination.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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 advanced solid malignancy
- •Patients enrolled in stratum II of the study must have BRCA1/2 mutation (added 04/07/09)
- •Patients with CNS metastases must be stable after therapy for CNS metastases (such as surgery, radiotherapy or stereotactic radiosurgery) for > 3 months and must be off steroid treatment prior to study enrollment
- •ECOG performance status 0-2
- •Life expectancy > 12 weeks
- •ANC ≥ 1,500/μL
- •Platelet count ≥ 100,000/μL
- •Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
- •AST and ALT ≤ 2.5 times ULN
- •Creatinine normal OR creatinine clearance ≥ 60 mL/min
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception during and for ≥ 3 months after completion of study treatment
- •More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
- •More than 3 weeks since prior radiotherapy
- •Prior veliparib allowed
排除标准
- •Known history of allergic reactions to veliparib, carboplatin, or Cremophor-paclitaxel
- •Uncontrolled intercurrent illness, including, but not limited to, any of the following:
- •Ongoing or active infection
- •Symptomatic congestive heart failure
- •Unstable angina pectoris
- •Cardiac arrhythmia
- •Psychiatric illness or social situations that would preclude compliance with study requirements
- •Peripheral neuropathy > grade 1
- •Inability to take oral medications on a continuous basis
- •Active seizure or history of seizure disorder
- •Evidence of bleeding diathesis
- •Received > 3 prior chemotherapy regimens for advanced stage disease for patients enrolled in stratum I (there is no upper limit on the number of prior regimens for patients enrolled in stratum II) (added 04/07/09)
- •Adjuvant chemotherapy administered ≥ 2 years prior to enrollment to the study does not count as a prior chemotherapy regimen
- •Other concurrent investigational agents
- •Concurrent combination antiretroviral therapy for HIV-positive patients
研究组 & 干预措施
Treatment (enzyme inhibitor therapy and chemotherapy)
Patients receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 3 and veliparib PO twice daily on days 1-7 until the recommended phase II dose is determined. Treatment repeats every 3 weeks for at least 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Veliparib (Drug)
Treatment (enzyme inhibitor therapy and chemotherapy)
Patients receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 3 and veliparib PO twice daily on days 1-7 until the recommended phase II dose is determined. Treatment repeats every 3 weeks for at least 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Carboplatin (Drug)
Treatment (enzyme inhibitor therapy and chemotherapy)
Patients receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 3 and veliparib PO twice daily on days 1-7 until the recommended phase II dose is determined. Treatment repeats every 3 weeks for at least 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (enzyme inhibitor therapy and chemotherapy)
Patients receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 3 and veliparib PO twice daily on days 1-7 until the recommended phase II dose is determined. Treatment repeats every 3 weeks for at least 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Paclitaxel (Drug)
Treatment (enzyme inhibitor therapy and chemotherapy)
Patients receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 3 and veliparib PO twice daily on days 1-7 until the recommended phase II dose is determined. Treatment repeats every 3 weeks for at least 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Pharmacological Study (Other)
结局指标
主要结局
Recommended phase II dose (RP2D) for each stratum
时间窗: Up to 4 weeks
The RP2D for each cohort will be defined by the study separately. Standard up \& down dose-escalation scheme to determine the RP2D will be use, and toxicities will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) v4.0.
次要结局
- Frequency of platinum-DNA adducts(At baseline and 4 weeks post-treatment)
- Incidence of stable disease (SD)(Measured from the start of the treatment until the criteria for progression are met, assessed up to 4 weeks post-treatment)
- Toxicities as assessed by CTCAE v.4.0(From the time of their first treatment with veliparib to up to 4 weeks post-treatment)
- Dose-limiting toxicity (DLT)(During course 1)
- Responses to veliparib in combination with carboplatin and paclitaxel(Up to 4 weeks post-treatment)
- PAR levels(Up to 4 weeks post-treatment)
- Time to progression (TTP)(Time from start of treatment to time of progression, assessed up to 4 weeks post-treatment)