Phase I Study of ABT-888 in Combination With Gemcitabine in Patients With Advanced Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 4
- 主要终点
- MTD of ABT-888 and gemcitabine hydrochloride, determined according to incidence of DLT graded using the NCI CTCAE version 4.0
研究概览
简要总结
This phase I trial is studying the side effects and best dose of giving ABT-888 together with gemcitabine hydrochloride in treating patients with advanced solid tumors. ABT-888 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving ABT-888 together with gemcitabine hydrochloride may kill more tumor cells.
详细描述
PRIMARY OBJECTIVES:
I. Establish the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLTs) of the combination of ABT-888 and gemcitabine (gemcitabine hydrochloride) in patients with advanced solid tumors.
SECONDARY OBJECTIVES:
I. Establish the safety and tolerability of the combination of ABT-888 and gemcitabine in patients with solid tumors.
II. Determine the effects of ABT-888 and gemcitabine treatment on DNA damage response by analysis of markers such as Ataxia telangiectasia mutated (ATM) in peripheral blood mononuclear cells (PBMCs).
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 confirmed solid tumors meeting 1 of the following criteria:
- •Progressive disease following standard therapy
- •Disease for which acceptable standard treatment options do not exist
- •May have received 0-2 prior chemotherapeutic regimens (single-agent or combination chemotherapies)
- •Willing to undergo BRCA mutation analysis
- •Known BRCA mutations allowed
- •All patients, at any dose level, without a known BRCA mutation undergo screening with the BRCAPRO program to assess the likelihood of having a BRCA mutation
- •Patients with a BRCAPRO likelihood of gene mutation of ≥ 20% must undergo BRCA gene testing by the Myriad Genetic Laboratories in order to participate in the study
- •Patients are eligible whether they have a known deleterious BRCA 1 or 2 mutation or a mutation of uncertain significance
- •No CNS disease (e.g., brain metastases or glioma)
- •No active seizure or history of seizure disorder
- •ECOG performance status 0-2 (Karnofsky 60-100%)
- •Life expectancy > 3 months
- •ANC ≥ 1,500/mm^3
- •Platelet count ≥ 100,000/mm^3
- •Bilirubin < 2.0 mg/dL
- •AST and ALT < 3 times upper limit of normal
- •Creatinine normal OR creatinine clearance > 50 mL/min
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •Able to swallow pills
- •HIV-positive patients allowed provided that CD4 counts are < 500 and not on protease inhibitors
- •No uncontrolled diarrhea
- •No 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 limit compliance with study requirements
- •No other concurrent anticancer therapies or agents
- •More than 4 weeks since prior major surgery, radiotherapy, or chemotherapy (6 weeks for mitomycin C or nitrosoureas) and recovered
- •Prior gemcitabine hydrochloride or PARP inhibition therapy, including ABT-888, allowed
- •No prior combination of gemcitabine hydrochloride and any PARP inhibitor
- •Concurrent bisphosphonate IV allowed provided treatment was initiated before study therapy (for patients with bone metastases or hypercalcemia)
- •Patients with prostate cancer must continue luteinizing-hormone releasing-hormone agonist therapy and discontinue antiandrogens (≥ 6 weeks since bicalutamide and ≥ 4 weeks since flutamide)
- •No other concurrent investigational agents
排除标准
- 未提供
研究组 & 干预措施
Treatment (gemcitabine hydrochloride and ABT-888)
Patients receive oral ABT-888 twice daily on days 1-14 and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Courses repeat every 21* days in the absence of disease progression or unacceptable toxicity.
干预措施: Diagnostic Laboratory Biomarker Analysis (Other)
Treatment (gemcitabine hydrochloride and ABT-888)
Patients receive oral ABT-888 twice daily on days 1-14 and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Courses repeat every 21* days in the absence of disease progression or unacceptable toxicity.
干预措施: Gemcitabine Hydrochloride (Drug)
Treatment (gemcitabine hydrochloride and ABT-888)
Patients receive oral ABT-888 twice daily on days 1-14 and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Courses repeat every 21* days in the absence of disease progression or unacceptable toxicity.
干预措施: Pharmacological Study (Other)
Treatment (gemcitabine hydrochloride and ABT-888)
Patients receive oral ABT-888 twice daily on days 1-14 and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Courses repeat every 21* days in the absence of disease progression or unacceptable toxicity.
干预措施: Veliparib (Drug)
结局指标
主要结局
MTD of ABT-888 and gemcitabine hydrochloride, determined according to incidence of DLT graded using the NCI CTCAE version 4.0
时间窗: 3 weeks
次要结局
- Response (complete or partial response)(Up to 4 weeks after completion of study treatment)
- Adverse events as assessed by NCI CTCAE v 4.0(Up to 4 weeks after completion of study treatment)
- Plasma concentrations of gemcitabine hydrochloride and ABT-888(Pre-drug, 25, 60, and 90 min, 2, 3, 4, 6, and 8 hours post-ABT-888 on day -2; pre-drug, 15, 25 (before end of gemcitabine infusion), 60, and 90 min, 2, 3, 4, 6, 8, 24, and 48 h after the start of gemcitabine hydrochloride infusion on day 1 of course 1)