A Study of ABT-888 in Combination With Carboplatin and Gemcitabine in Subjects With Advanced Solid Tumors

Study Overview
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Brief Summary
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The purpose of this study is to determine the maximum tolerated dose of veliparib (ABT-888)and to establish the recommended Phase 2 dose of veliparib (ABT-888) when administered in combination with carboplatin and gemcitabine in subjects with advanced solid tumors.

Official Title
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A Phase 1 Study of Veliparib in Combination With Carboplatin and Gemcitabine in Subjects With Advanced Solid Tumors

Conditions
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Advanced Solid Tumors

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed solid tumors that are metastatic or unrespectable for which carboplatin/gemcitabine is a treatment option. Eastern Cooperative Group performance score of 0 to 2. Adequate hematologic, hepatic and renal function Subject has received up to 2 DNA damaging or cytotoxic regimens in the past five years Exclusion Criteria: Subject has received any anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, biologic or any investigational therapy within 28 days prior to study administration. Subjects with known history of brain metastases and primary CNS tumors. Hypersensitivity reactions to platinum compounds or gemcitabine. Clinically significant and uncontrolled major medical conditions Active malignancy within the past 5 years except for any cancer in situ cured or non-melanoma carcinoma of the skin.

Ages Eligible for Study
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Minimum Age: 18 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: Arm 1<br> | Drug: veliparib (ABT-888)<br>* Dosing orally twice daily starting Cycle 2 Day 1- through 21 adjusted for subsequent cohorts using a continuous reassessment method.<br>Drug: carboplatin<br>* Carboplatin will be dosed on Day 1 of each cycle, intravenously.<br>Drug: gemcitabine<br>* Dosing on Days 1 and 8 of each Cycle, intravenously.<br>* Other names: Gemzar;|

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 2 dose |  | ABT-888 will be dose escalated until the largest dose is reached based on the probability of dose, limiting toxicities is based per continual reassessment method (CRM). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics Area Under the Curve (AUC) |  | Timepoints: 30 and 45 minutes, 1,1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5,6,6.5, 7 and 8 hours past dose | 
| Safety assessment: Electrocardiogram |  | Screening, Day 8 of each Cycle of drug and Final Visit | 
| Safety assessment: Clinical Laboratory Tests | Hematology and Chemistry | Screening, Day 1 and Day 8 of each cycle, Final Visit and 30 Day Follow-up Visit | 
| Physical exam including vital signs | Physical exam including blood pressure, pulse and temperature | Screening, Cycle 1 Day 8, Day 1 of all cycles starting with Cycle2, Final Visit and 30 Day Follow-up Visit | 
| Safety assessment: Adverse event assessments | Collect all adverse events at each visit | All study visits | 
| Tumor assessment | Computerized tomography (CT) scan of chest, abdomen and pelvis to assess tumor burden | Screening, every nine weeks and Final Visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PARP Inhibitors