Study Comparing Veliparib Plus Carboplatin and Paclitaxel Versus Placebo Plus Carboplatin and Paclitaxel in Previously Untreated Advanced or Metastatic Squamous Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of the addition of veliparib plus carboplatin and paclitaxel versus the addition of placebo plus carboplatin and paclitaxel in adults with advanced or metastatic squamous non-small cell lung cancer (NSCLC).

Official Title
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Randomized, Double-Blind, Multicenter, Phase 3 Study Comparing Veliparib Plus Carboplatin and Paclitaxel Versus Placebo Plus Carboplatin and Paclitaxel in Previously Untreated Advanced or Metastatic Squamous Non-Small Cell Lung Cancer (NSCLC)

Conditions
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Squamous Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Carboplatin
* Drug: Veliparib
* Drug: Paclitaxel
* Drug: Placebo to veliparib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Life expectancy > 12 weeks Subject must have cytologically or histologically confirmed squamous NSCLC. Subject must have advanced or metastatic squamous NSCLC that is not amenable to surgical resection or radiation with curative intent at time of study Screening. Subjects with recurrent squamous NSCLC after surgical treatment that is not amenable to surgical resection or radiation with curative intent are eligible. Subject must have at least 1 unidimensional measurable NSCLC lesion on a computerized tomography (CT) scan as defined by Response Evaluation Criteria In Solid Tumors (RECIST - version 1.1). Exclusion Criteria: Subject has a known hypersensitivity to paclitaxel or to other drugs formulated with polyethoxylated castor oil (Cremophor). Subject has a known hypersensitivity to platinum compounds. Subject has peripheral neuropathy >= grade 2. Subject has non-squamous NSCLC, or a known epidermal growth factor receptor (EGFR) mutation of exon 19 deletion or L858R mutation in exon 21, or a known anaplastic lymphoma kinase (ALK) gene rearrangement. Subject has received prior cytotoxic chemotherapy (including definitive chemoradiotherapy) for NSCLC, except for adjuvant or neoadjuvant therapy.

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: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Veliparib + Carboplatin + Paclitaxel<br>Participants received veliparib 120 mg orally twice daily (BID) on Days -2 to 5 (7 consecutive days) of each 21-day cycle and carboplatin at an area under the concentration-time curve (AUC) 6 mg/mL/min and paclitaxel 200 mg/m² by intravenous (IV) infusion on Day 1 of each 21-day cycle for up to a maximum 6 cycles of treatment, until treatment toxicity which, in the Investigator's opinion, prohibited further therapy, or until radiographic progression. | Drug: Carboplatin<br>* Carboplatin administered intravenously over approximately 15 to 30 minutes at (AUC 6 mg/mL/min) immediately following paclitaxel infusion.<br>Drug: Veliparib<br>* Capsules taken orally twice a day, 12 hours apart.<br>* Other names: ABT-888;Drug: Paclitaxel<br>* Paclitaxel administered intravenously over 3 hours at a dose of 200 mg/m².<br>|
| Placebo Comparator: Placebo + Carboplatin + Paclitaxel<br>Participants received placebo orally BID on Days -2 to 5 (7 consecutive days) of each 21-day cycle and carboplatin at an AUC 6 mg/mL/min and paclitaxel 200 mg/m² by IV infusion on Day 1 of each 21-day cycle for up to a maximum 6 cycles of treatment, until treatment toxicity which, in the Investigator's opinion, prohibited further therapy, or until radiographic progression. | Drug: Carboplatin<br>* Carboplatin administered intravenously over approximately 15 to 30 minutes at (AUC 6 mg/mL/min) immediately following paclitaxel infusion.<br>Drug: Paclitaxel<br>* Paclitaxel administered intravenously over 3 hours at a dose of 200 mg/m².<br>Drug: Placebo to veliparib<br>* Capsules taken orally twice a day, 12 hours apart.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) in current smokers | Time to death for a given subject will be defined as the number of days from the date that the subject was randomized to the date of the subject's death. | Up to 3 years from first dose of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) in all subjects | Time to death for a given subject will be defined as the number of days from the date that the subject was randomized to the date of the subject's death. | Up to 3 years from first dose of study drug | 
| Progressive-Free Survival (PFS) in current smokers and in all subjects | Defined as the number of days from the date that the subject was randomized to the date the subject experiences an event of disease progression or to the date of death (all causes of mortality) if disease progression is not reached. | Up to 3 years from first dose of study drug | 
| Objective Response Rate (ORR) in current smokers and in all subjects | Objective response rate is defined as the proportion of subjects with complete or partial response as determined by the investigator per RECIST (version 1.1) | Up to 3 years from first dose of study drug | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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veliparib, carboplatin, paclitaxel, Poly Adenosine diphosphate (ADP)-ribose Polymerase (PARP), Overall Survival, Advanced, Metastatic, ABT-888, Squamous, Randomized, non-small cell lung cancer, placebo controlled