A Study of Veliparib in Combination With Carboplatin and Paclitaxel in Japanese Subjects With Solid Tumors

Study Overview
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Brief Summary
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This is a Phase 1 open-label study and consists of 3 treatment groups (dose levels) . Treatment cycles are 3 weeks in duration. The primary objective of this study is to determine the recommended phase two dose (RPTD) of veliparib (ABT-888) when administered in combination with carboplatin and paclitaxel in Japanese subjects with solid tumors. Secondary objectives are to assess pharmacokinetics and to obtain a preliminary efficacy of anti-tumor activity in the subjects.

Official Title
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A Phase 1 Study of Veliparib (ABT-888) in Combination With Carboplatin/Paclitaxel in Japanese Subjects With Solid Tumors

Conditions
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Solid Tumors

Intervention / Treatment
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* Drug: veliparib (ABT-888)
* Drug: carboplatin
* Drug: paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have histologically or cytologically confirmed malignant solid tumor. Patients who are amenable to standard combination chemotherapy of carboplatin and paclitaxel. Patients should have received less than or equal to 1 prior chemotherapy regimens for advanced stage disease. Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2. Patients must have normal organ and marrow function Exclusion Criteria: Patients who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or the adverse events due to agents administered more than 3 weeks earlier have not recovered to less than grade 2. Known history of allergic reactions to carboplatin or cremophor-paclitaxel. Patients who have previously received a poly(ADP-ribose) polymerase (PARP) inhibitor. Uncontrolled intercurrent illness including, but not limited to, ongoing or active systemic infection requiring treatment, symptomatic congestive heart failure, angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. History of seizure disorder. Hepatitis B surface antigen (HBsAg) positive, Hepatitis C virus (HCV) antibody positive or Human immunodeficiency virus (HIV)-positive patients.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: veliparib (ABT-888)<br> | Drug: veliparib (ABT-888)<br>* Dosing orally twice daily starting Day 1 through day 7 of each cycle. Decisions to move to the next cohort will be based on evaluation of DLTs in the current cohort. Decisions will be made with a discussion between the Sponsor and the principal investigator to dose escalate or de-escalate or add more subjects to the cohort.<br>Drug: carboplatin<br>* Carboplatin will be administered on Day 3 of each cycle, intravenously.<br>* Other names: paraplatin;Drug: paclitaxel<br>* Paclitaxel will be administered on Day 3 of each cycle, intravenously.<br>* Other names: taxol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the maximum tolerated dose and recommended Phase two dose |  | During the first cycle (21 days from first dose of veliparib) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics; Area Under the Curve (AUC), Maximum observed plasma concentration (Cmax) and Time to Cmax (Tmax) of veliparib (ABT-888) |  | Eight timepoints on Day 1 of first cycle (21 days) | 
| Pharmacokinetics; Area Under the Curve (AUC), Maximum observed plasma concentration (Cmax) and Time to Cmax (Tmax) of veliparib (ABT-888) when administered in combination with carboplatin and paclitaxel |  | Eight timepoints on Day 3 of first cycle (21 days) | 
| Pharmacokinetics; Area Under the Curve (AUC), Maximum observed plasma concentration (Cmax) and Time to Cmax (Tmax) of paclitaxel when administered in combination with veliparib (ABT-888) and carboplatin |  | Eight timepoints on Day 3 of first cycle (21 days) | 
| Pharmacokinetics; Area Under the Curve (AUC), Maximum observed plasma concentration (Cmax) and Time to Cmax (Tmax) of carboplatin when administered in combination with veliparib (ABT-888) and paclitaxel |  | Six timepoints on Day 3 of first cycle (21 days) | 
| Preliminary tumor response | Computerized tomography (CT) scan of chest, abdomen and pelvis to assess tumor burden | From date of first dose of veliparib until the date of first documented progression or date of death from any cause, whichever come first, assessed up to 6 cycles. | 
| Safety assessment; Physical exam including vital signs | Blood pressure, pulse and body temperature | From date of first dose of veliparib until 30 days after last dose of veliparib (up to 6 cycles) | 
| Safety assessment; Clinical lab testings | Hematology, Chemistry and Urinalysis | From date of first dose of veliparib until 30 days after last dose of veliparib (up to 6 cycles) | 
| Safety assessment; Adverse event monitoring | Collect all adverse events at each visit | From date of first dose of veliparib until 30 days after last dose of veliparib (up to 6 cycles) | 
| Safety assessment; Change from Baseline in Electrocardiogram (ECG) |  | Day 8 of first cycle (21 days) |