Veliparib in Combination With Carboplatin and Paclitaxel in Treating Patients With Locally Advanced or Metastatic Solid Tumors
A Phase 1 Study of ABT-888 (Veliparib) in Combination With Weekly Carboplatin and Paclitaxel in Advanced Solid Tumors
研究概览
地位
干预/治疗
详细说明
PRIMARY OBJECTIVE:
I. To determine the maximum-tolerated dose (MTD) of the combination of weekly carboplatin, paclitaxel, and veliparib.
SECONDARY OBJECTIVES:
I. To assess the safety, tolerability, and MTD of the combination of weekly carboplatin, paclitaxel, and veliparib.
II. To assess the safety and toxicity of this combination as determined by the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v. 4.0) and to determine the dose-limiting toxicity (DLT).
III. To determine the pharmacokinetic and pharmacodynamic effects of this combination, including determinations of poly (adenosine diphosphate [ADP]-ribose) polymerase (PAR) in tumor specimens when available, assessment of deoxyribonucleic acid (DNA) damage as measured by gamma H2A histone family, member X (g-H2AX) in skin biopsies and tumor specimens will be obtained.
IV. To assess characteristics of primary tumor specimens that may contribute to efficacy of this combination including breast cancer, early onset (BRCA) by immunohistochemistry, gene analysis of PARP 1, PARP 2, BRCA, and triple negative and homologous recombination repair (HRR) deficiency gene expression signatures.
V. To document any anti-tumor response.
OUTLINE: This is a dose-escalation study of veliparib.
DOSE-ESCALATION: Patients receive veliparib orally (PO) twice daily (BID) on days 1-5, 8-12, and 15-19 and paclitaxel IV over 1 hour and carboplatin IV over 30 minutes in course 1 and 3 hours in subsequent courses on days 3, 10, and 17. After 4 courses, patients receive paclitaxel and carboplatin on days 3 and 10 only. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. (Completed as of 12/2012)
EXPANSION COHORT: Patients receive veliparib PO BID on days 1-21 and paclitaxel IV over 1 hour and carboplatin IV over 3 hours on days 3 and 10. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study therapy, patients are followed up for 4 weeks.
研究类型
注册 (实际的)
阶段
- 阶段1
联系人和位置
学习地点
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Pennsylvania
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Hershey、Pennsylvania、美国、17033-0850
- Penn State Milton S Hershey Medical Center
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Pittsburgh、Pennsylvania、美国、15213
- UPMC-Magee Womens Hospital
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Pittsburgh、Pennsylvania、美国、15232
- University of Pittsburgh Cancer Institute (UPCI)
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
Histologically or cytologically confirmed solid tumor that has evidence of metastatic spread (stage IV) or is locally advanced and unresectable
- Patients with breast cancer may have estrogen receptor positive or negative (ER+ or ER-) disease
- Patients with breast cancer may not be human epidermal growth receptor -2 (HER2)-positive ( 3+), or fluorescent in situ hybridization (FISH) ratio > 2.2
Patients in the biopsy expansion cohort must have "triple negative" breast cancer defined as:
- Estrogen receptor staining < 10%; progesterone receptor staining <10%; Her 2 < 2.2 by FISH, or immunohistochemistry (IHC) 0-2+
Patients may have been previously treated
- In the dose escalation cohort, there is no limit to prior therapies
- In the expansion cohort, patients may have only had 1-3 prior regimens for metastatic disease
Patients may have received prior carboplatin, paclitaxel, or poly (ADP-ribose) polymerase (PARP) inhibitor therapy as part of their previous treatment regimens
- However, patients may NOT have received prior therapy with paclitaxel, carboplatin, and PARP inhibitor in combination
- Patients must not have received chemotherapy within 4 weeks of starting study (or 6 weeks if prior treatment was with carmustine [BCNU] or mitomycin C)
- Patients must not have received radiation within 2 weeks of starting study
- Eastern Cooperative Oncology Group (ECOG) performance status (PS)< 2 (Karnofsky > 60%)
- Life expectancy > 2 months
- Absolute neutrophil count (ANC) >= 1,500/mcL
- Platelet count >= 100,000/mcL
- Total bilirubin =< 1.5 times upper limit of normal (ULN)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 times ULN
- Creatinine normal within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73m^2 for patients with creatinine levels above institutional normal
- Must able to swallow pills
Pregnant women are excluded from this study
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- Ability to understand and the willingness to sign a written informed consent document
Patients enrolled in the expanded cohort with mandatory biopsies must:
- Have accessible tumors
- Not be on therapeutic anticoagulation
- Have signed informed consent form
Exclusion Criteria:
- Patients who have had chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) or radiotherapy within 2 weeks (4 weeks for central nervous system [CNS] metastases) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- Patients may not be receiving any other investigational agents
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to veliparib or other agents used in study
- Concurrent treatment with bisphosphonates, or other bone anti-resorptive agent such as denosumab is allowed; concurrent treatment with hormonal therapy (tamoxifen, ovarian suppression with gonadotropin-releasing hormone [GNRH] agonists, aromatase inhibitors) or trastuzumab therapy is NOT allowed in breast cancer patients; prostate cancer patients may continue GNRH agents
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with veliparib
- Active seizure or history of seizure disorder
- 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
- Patients who undergo biopsy as part of the study in the expanded dose cohort should not be on anti-coagulants or have a pre-existing coagulopathy
- Peripheral neuropathy of severity greater than grade 1
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:不适用
- 介入模型:单组作业
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的:Treatment (veliparib, paclitaxel, carboplatin)
DOSE-ESCALATION: Patients receive veliparib PO twice daily BID on days 1-5, 8-12, and 15-19 and paclitaxel IV over 1 hour and carboplatin IV over 30 minutes in course 1 and 3 hours in subsequent courses on days 3, 10, and 17. After 4 courses, patients receive paclitaxel and carboplatin on days 3 and 10 only. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. (Completed as of 12/2012) EXPANSION COHORT: Patients receive veliparib PO BID on days 1-21 and paclitaxel IV over 1 hour and carboplatin IV over 3 hours on days 3 and 10. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. |
相关研究
鉴于IV
其他名称:
相关研究
鉴于IV
其他名称:
给定采购订单
其他名称:
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研究衡量的是什么?
主要结果指标
结果测量 |
大体时间 |
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MTD defined as the dose level one level below the lowest dose where greater than or equal to 2 patients experience a DLT assessed by National Cancer Institute (NCI) CTCAE v. 4.0
大体时间:21 days
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21 days
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Change in BRCA protein levels by immunohistochemistry
大体时间:Baseline to day 4 of course 2
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Calculated and compared using the Wilcoxon rank sum test.
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Baseline to day 4 of course 2
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Change in PAR and g-H2AX in tumor tissue
大体时间:Baseline to day 4 of course 2
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Assessed with Wilcoxon signed rank tests.
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Baseline to day 4 of course 2
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Grade >= 3 non-hematological or any grade 5 DLTs as graded by the NCI CTCAE v. 4.0
大体时间:21 days
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Statistics on the number of cycles received by patients and any dose reductions will be tabulated.
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21 days
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Incidence of adverse events as graded by the NCI CTCAE v. 4.0
大体时间:Up to 4 weeks post-treatment
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The maximum grade of toxicity for each category of interest will be recorded for each patient and the summary results will be tabulated by category and grade.
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Up to 4 weeks post-treatment
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Plasma concentration of carboplatin, paclitaxel, and veliparib using liquid chromatography-mass spectrometry (LC-MS) assay and spectrometry assay
大体时间:Baseline, at 30 minutes and at 1, 2, 4, and 8 hours on day 3 of course 1
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Baseline, at 30 minutes and at 1, 2, 4, and 8 hours on day 3 of course 1
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Response complete response [Cr], partial response [PR], and stable disease [SD]) using the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)
大体时间:Up to 4 weeks post-treatment
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CR, PR, and incidence of SD will be tabulated by disease diagnosis and by dose level.
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Up to 4 weeks post-treatment
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合作者和调查者
调查人员
- 首席研究员:Shannon Puhalla、University of Pittsburgh Cancer Institute (UPCI)
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- NCI-2011-02490 (注册表标识符:CTRP (Clinical Trial Reporting Program))
- U01CA099168 (美国 NIH 拨款/合同)
- P30CA047904 (美国 NIH 拨款/合同)
- CDR0000693333
- 09-084 (其他标识符:University of Pittsburgh Cancer Institute (UPCI))
- 8620 (其他标识符:CTEP)
此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.
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