Study of Carboplatin/Paclitaxel in Combination With ABT-869 in Subjects With Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)

Study Overview
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Brief Summary
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This study is designed to determine the clinical efficacy and toxicity of ABT-869 in combination with carboplatin and paclitaxel in the treatment of subjects with advanced or metastatic NSCLC.

Official Title
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A Phase 2 Randomized, Placebo-Controlled, Double-Blind Study of Carboplatin/Paclitaxel in Combination With ABT-869 Versus Carboplatin/Paclitaxel Alone in Subjects With Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) as First-Line Treatment

Conditions
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Advanced or Metastatic Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: ABT-869
* Drug: Placebo for ABT-869
* Drug: ABT-869
* Drug: Carboplatin
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must be at least 18 years of age. Subject must have cytologically or histologically confirmed non-squamous NSCLC Subject must have recurrent or advanced (Stage IIIb with pleural or pericardial effusion) or metastatic (Stage IV) disease that is not amenable to surgical resection or radiation with curative intent. Subject has measurable disease, defined as at least 1 unidimensional measurable lesion on a computed tomography (CT) scan as defined by RECIST (for subjects in the randomized portion only). Subject has an ECOG Performance Score of 0-1. Willing to take adequate measures to prevent pregnancy. Exclusion Criteria: The subject has NSCLC with a predominant squamous cell histology Subject has hypersensitivity to paclitaxel. Subject has received any anti-cancer therapy for treatment of NSCLC. Subject has received radiation therapy within 21 days of Study Day 1. Subject has had major surgery within 21 days. Subject has untreated brain or meningeal metastases. Subject is receiving therapeutic anticoagulation therapy. Subject has a central thoracic tumor lesion as defined by location within the hilar structures. Subject has proteinuria CTC Grade > 1 at baseline. Subject has a history of, or currently exhibits clinically significant cancer related events of bleeding. The subject currently exhibits symptomatic or persistent, uncontrolled hypertension defined as diastolic blood pressure (BP) > 90 mm Hg or systolic BP > 140 mm Hg. The subject has a history of myocardial infarction, stroke or Transient Ischemic Attack (TIA) within 6 months of Study Day 1. The subject has a documented left ventricular (LV) ejection fraction < 50%. The subject has known autoimmune disease with renal involvement (i.e., lupus). The subject is receiving combination anti-retroviral therapy for HIV. The subject has clinically significant uncontrolled condition(s). The subject has a history of another active cancer within the past 5 years. The subject has active ulcerative colitis, Crohn's disease, celiac disease or any other conditions that interfere with absorption. The subject has a medical condition, which in the opinion of the study investigator places them at an unacceptably high risk for toxicities. The subject is pregnant or breast feeding.

Ages Eligible for Study
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Minimum Age: 18 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>12.5 mg ABT-869 + Carboplatin/Paclitaxel | Drug: ABT-869<br>* 12.5 mg ABT-869<br>Drug: Carboplatin<br>* Carboplatin (AUC 6 mg/mL/min)<br>Drug: Paclitaxel<br>* Paclitaxel (200 mg/m2)<br>|
| Experimental: B<br>7.5 mg ABT-869 + Carboplatin/Paclitaxel | Drug: ABT-869<br>* 7.5 mg ABT-869<br>Drug: Carboplatin<br>* Carboplatin (AUC 6 mg/mL/min)<br>Drug: Paclitaxel<br>* Paclitaxel (200 mg/m2)<br>|
| Placebo Comparator: C<br>Placebo (7.5 mg or 12.5 mg) + Carboplatin/Paclitaxel | Drug: Placebo for ABT-869<br>* Placebo Comparator (12.5 mg or 7.5 mg)<br>* Other names: Placebo;Drug: Carboplatin<br>* Carboplatin (AUC 6 mg/mL/min)<br>Drug: Paclitaxel<br>* Paclitaxel (200 mg/m2)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) |  | Disease Progression | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival, best response rate, time to tumor progression, objective response rate, best percent change in tumor size, duration of response |  | Disease Progression | 
| Survival Rate |  | 12 Months |