A Study Evaluating Veliparib as a Single Agent or in Combination With Chemotherapy in Subjects With Solid Tumors

Study Overview
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Brief Summary
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This is an extension study to evaluate the safety of Veliparib monotherapy or in combination with Carboplatin plus Paclitaxel or modified Folinic Acid/Fluorouracil/Irinotecan (FOLFIRI) in subjects with solid tumors.

Official Title
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An Extension Study to Evaluate the Safety of Veliparib as Single Agent Therapy or in Combination With Chemotherapy in Subjects With Solid Tumors

Conditions
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Breast Cancer, Ovarian Cancer, Colon Cancer, Lung Cancer, Gastric Cancer, Solid Tumors

Intervention / Treatment
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* Drug: Veliparib
* Drug: Carboplatin
* Drug: Paclitaxel
* Drug: FOLFIRI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must have confirmed solid malignancy that is metastatic, and standard curative measures or other therapy that may provide clinical benefit do not exist or are no longer effective. For Veliparib monotherapy (must have tumor with defects in DNA repair mechanisms (BRCA mutation or high grade ovarian cancer or solid tumors for combination therapy. If the subject has known brain metastases must have clinically controlled neurologic symptoms, defined as surgical excision and/or radiation therapy followed by 21 days of stable neurologic function and no evidence of Central Nervous System (CNS) disease progression as determined by comparing a computed tomography (CT) scan or magnetic resonance imaging (MRI) scan performed during screening to a prior scan performed at least 4 weeks earlier and provided that the subject is asymptomatic, has no evidence of cavitation or hemorrhage, and does not require corticosteroids (must have discontinued steroids at least 3 months prior to study drug administration). Subject must have adequate bone marrow, renal and hepatic function per local laboratory reference range. Exclusion Criteria: Subject has a clinically significant and uncontrolled major medical condition(s) including but not limited to: Uncontrolled seizure disorder, including focal or generalized seizure within the last 12 months; Uncontrolled nausea/vomiting/diarrhea; Active uncontrolled infection; Symptomatic congestive heart failure; Unstable angina pectoris or cardiac arrhythmia; Psychiatric illness/social situation that would limit compliance with study requirements; Any medical condition, which in the opinion of the study investigator, places the subject at an unacceptably high risk for toxicities. Subjects who have hypersensitivity to Carboplatin, Paclitaxel or Cremophor should be excluded from arm B. Subject has received any of the following anti-cancer therapies 21 days prior to the first dose of study drug or a biologic agent for anti-neoplastic intent within 30 days prior to the first dose of study drug. Subject who requires parenteral nutrition, tube feeding or has evidence of a partial bowel obstruction or perforation within 28 days prior to study drug. The subject has had another active malignancy within the past 3 years except for any cancer in situ that the Principal Investigator considers to be cured.

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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A - Veliparib Monotherapy<br>Subjects in this arm will be dosed with Veliparib continuous dosing. | Drug: Veliparib<br> <br> * Other names: ABT-888;|
| Experimental: Arm B - Veliparib in Combination with Carboplatin & Paclitaxel<br>Subjects enrolled will receive Veliparib in combination with Carboplatin and Paclitaxel and have an option to move to Veliparib monotherapy. | Drug: Veliparib<br> <br> * Other names: ABT-888;Drug: Carboplatin<br> <br> Drug: Paclitaxel<br> <br> * Other names: Taxol;|
| Experimental: Arm C Veliparib in Combination with Modified FOLFIRI<br>Subjects will be given Veliparib in combination with modified FOLFIRI. The subject will have the opportunity to receive Veliparib as monotherapy. | Drug: Veliparib<br> <br> * Other names: ABT-888;Drug: FOLFIRI<br>* combination of Fluorouracil, leucovorin and irinotecan<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with adverse events |  | Measured up to 30 days after the last dose of study drug. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) |  | Radiographic evaluation at Screening and every 6-9 weeks until the final visit, up to 18 months. | 
| Overall Survival (OS) |  | Every 3 months after the subject is registered off study up to 2 years post discontinuation or until date of death from any cause, whichever comes first. | 
| Time to Disease Progression (TTP) |  | Assessed at each visit up to 18 months after the last subject has enrolled in the study. | 
| Progression Free Survival (PFS) |  | Radiographic evaluation starting from the first day of study drug until documented progression or date of death, whichever comes first, until the subject is registered off study. | 
| Clinical Laboratory Tests | Hematology, Chemistry, Urinalysis | Up to 18 months. | 
| Electrocardiogram |  | Up to 18 months. | 
| Tumor Assessment | A computerized tomography scan to document the size of the tumor. | Up to 18 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lung Cancer, Gastric Cancer, PARP Inhibitor, Ovarian Cancer, Solid Tumors, Breast Cancer, Colon Cancer