Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

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.

Further Study Information

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.

III. To evaluate the pharmacokinetic parameters of veliparib, carboplatin, and paclitaxel when administered as a combination.

IV. To conduct correlative science studies.

OUTLINE: This is a multicenter, dose-escalation study of veliparib. Patients are stratified according to BRCA status (no [stratum I] vs yes [stratum II]).

Patients receive carboplatin intravenously (IV) over 30 minutes and paclitaxel IV over 3 hours on day 3 and veliparib orally (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.

Patients undergo peripheral blood mononuclear cell collection periodically for pharmacokinetic and biomarker studies.

After completion of study treatment, patients are followed up for 4 weeks.

Eligibility Criteria

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Trial Contact Information

Trial Lead Organizations/Sponsors

National Cancer Institute

Suresh Ramalingam

Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00535119
Information obtained from ClinicalTrials.gov on March 26, 2013

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