Veliparib, Carboplatin, and Paclitaxel in Treating Patients With Advanced Solid Cancer
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|ClinicalTrials.gov Identifier: NCT00535119|
Recruitment Status : Completed
First Posted : September 26, 2007
Last Update Posted : May 22, 2015
|Condition or disease||Intervention/treatment||Phase|
|Adult Solid Neoplasm BRCA1 Mutation Carrier BRCA2 Mutation Carrier Hereditary Breast and Ovarian Cancer Syndrome||Drug: Carboplatin Other: Laboratory Biomarker Analysis Drug: Paclitaxel Other: Pharmacological Study Drug: Veliparib||Phase 1|
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)
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||107 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1 Study of ABT-888 in Combination With Carboplatin and Paclitaxel in Advanced Solid Malignancies|
|Study Start Date :||September 2007|
|Actual Primary Completion Date :||October 2012|
Experimental: 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.
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
- 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.
- Dose-limiting toxicity (DLT) [ Time Frame: During course 1 ]Toxicities should be attributable to the study drug(s) to constitute DLT. Patients will be considered evaluable for DLT if they are eligible, and if they receive any amount of treatment and experience DLT or complete the first course of treatment
- Frequency of platinum-DNA adducts [ Time Frame: At baseline and 4 weeks post-treatment ]Changes will be summarized as means and standard deviations. A statistical test of the null hypothesis of no change in each variable will be done using the Wilcoxon signed-ranks procedure. Measurements of the two variables at additional time points will be analyzed in a descriptive fashion using tables and plots.
- Incidence of stable disease (SD) [ Time Frame: Measured from the start of the treatment until the criteria for progression are met, assessed up to 4 weeks post-treatment ]SD is defined as neither sufficient shrinkage to qualify for partial response (PR) nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum longest diameter (LD) since the treatment started.
- PAR levels [ Time Frame: Up to 4 weeks post-treatment ]Changes will be summarized as means and standard deviations. A statistical test of the null hypothesis of no change in each variable will be done using the Wilcoxon signed-ranks procedure. Measurements of the two variables at additional time points will be analyzed in a descriptive fashion using tables and plots.
- Responses to veliparib in combination with carboplatin and paclitaxel [ Time Frame: Up to 4 weeks post-treatment ]Response will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. Only those patients who have measurable disease present at baseline, have received at least one cycle of therapy, and have had their disease re-evaluated will be considered evaluable for response.
- Time to progression (TTP) [ Time Frame: Time from start of treatment to time of progression, assessed up to 4 weeks post-treatment ]Progression will be evaluated in this study using the new international criteria proposed by RECIST. TTP will be displayed for all patients and for patients who have responded; no formal statistical analysis is planned.
- Toxicities as assessed by CTCAE v.4.0 [ Time Frame: From the time of their first treatment with veliparib to up to 4 weeks post-treatment ]Toxicities will be defined as regimen-related if they are possibly, probably or definitely related to treatment. 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, grade and dose level. Serious (≥ Grade 3) toxicities will be described on a patient-by-patient basis and will include any relevant baseline data.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00535119
|United States, California|
|City of Hope Comprehensive Cancer Center|
|Duarte, California, United States, 91010|
|USC / Norris Comprehensive Cancer Center|
|Los Angeles, California, United States, 90033|
|University of California Davis Comprehensive Cancer Center|
|Sacramento, California, United States, 95817|
|United States, Georgia|
|Emory University/Winship Cancer Institute|
|Atlanta, Georgia, United States, 30322|
|United States, Pennsylvania|
|Penn State Milton S Hershey Medical Center|
|Hershey, Pennsylvania, United States, 17033-0850|
|University of Pittsburgh Cancer Institute (UPCI)|
|Pittsburgh, Pennsylvania, United States, 15232|
|University of Pittsburgh Cancer Institute|
|Pittsburgh, Pennsylvania, United States, 15232|
|Principal Investigator:||Suresh Ramalingam||University of Pittsburgh Cancer Institute (UPCI)|