A Phase 1 Study of ABT-888 in Combination With Carboplatin and Paclitaxel in Advanced Solid Malignancies
Overview
- Phase
- Phase 1
- Intervention
- Veliparib
- Conditions
- Adult Solid Neoplasm
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 107
- Locations
- 7
- Primary Endpoint
- Recommended phase II dose (RP2D) for each stratum
- Status
- Completed
- Last Updated
- 10 years ago
Overview
Brief 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.
Detailed Description
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.
Investigators
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
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
Arms & Interventions
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.
Intervention: Veliparib
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.
Intervention: Carboplatin
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.
Intervention: Laboratory Biomarker Analysis
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.
Intervention: Paclitaxel
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.
Intervention: Pharmacological Study
Outcomes
Primary Outcomes
Recommended phase II dose (RP2D) for each stratum
Time Frame: 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.
Secondary Outcomes
- 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)