A Study of Bevacizumab Versus Placebo in Combination With Carboplatin/Paclitaxel in Participants With Advanced or Recurrent Non-Squamous Non-Small Cell Lung Cancer Who Have Not Received Previous Chemotherapy

Study Overview
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Brief Summary
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This randomized, double-blind, placebo-controlled study will evaluate the efficacy and safety of bevacizumab (Avastin) versus placebo in combination with carboplatin/paclitaxel in participants with advanced or recurrent non-squamous non-small cell lung cancer who have not received prior chemotherapy for advanced disease. Participants will be randomized to receive either bevacizumab 15 milligrams per kilogram (mg/kg) intravenously (IV) or placebo on Day 1 of each 3 week cycle, plus up to 6 cycles of carboplatin/paclitaxel. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs. After progression, participants in the bevacizumab arm may continue to receive bevacizumab in combination with approved second- and third-line treatment at the discretion of the investigator, up to the third progression.

Official Title
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A Randomized, Double-blinded, Placebo-controlled, Multicenter Phase III Study Comparing Bevacizumab Plus Carboplatin/Paclitaxel Versus Placebo Plus Carboplatin/Paclitaxel in Patients With Advanced or Recurrent Non-Squamous Non-Small Cell Lung Cancer Who Have Not Received Prior Chemotherapy For Advanced Disease

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Bevacizumab
* Drug: Carboplatin
* Drug: Paclitaxel
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Locally advanced (Stage IIIb not amenable for combined modality treatment), metastatic (Stage IV) or recurrent non-squamous non-small cell lung cancer Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 Adequate hematological, renal and liver function Exclusion Criteria: Prior chemotherapy or treatment with another systemic anti-cancer agent for the treatment of the participant's current stage of the disease (Stage IIIb, IV or recurrent disease) Mixed non-small cell and small cell tumors or mixed adenosquamous carcinomas with a predominant squamous component Evidence of tumor invading major blood vessels on imaging Central nervous system (CNS) metastases, even if previously treated History of hemoptysis in the 3 months prior to enrollment History or evidence of inherited bleeding diathesis or coagulopathy Uncontrolled hypertension and/or history of hypertensive crisis or hypertensive encephalopathy Clinically significant cardiovascular or vascular disease Malignancies other than non-small cell lung cancer within 5 years prior to randomization, except for adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, or localized prostate cancer or ductal carcinoma in situ treated surgically with curative intent

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: Bevacizumab + Paclitaxel/Carboplatin<br>Participants will receive bevacizumab on Day 1 of each 3-week cycle in combination with paclitaxel and carboplatin for the first 6 treatment cycles (cycle length = 21 days). Participants will continue to receive bevacizumab on Day 1 of each 3-week cycle until disease progression or unacceptable toxicity. | Drug: Bevacizumab<br>* Bevacizumab will be administered at 15 mg/kg IV on Day 1 of each 3-week cycle until disease progression or unacceptable toxicity.<br>* Other names: Avastin;Drug: Carboplatin<br>* Carboplatin will be administered at area under the plasma concentration-time curve (AUC) 6.0 IV on Day 1 of each 3-week cycle, up to 6 cycles.<br>Drug: Paclitaxel<br>* Paclitaxel will be administered at 175 milligrams per square meter (mg/m^2) IV on Day 1 of each 3-week cycle, up to 6 cycles.<br>|
| Active Comparator: Placebo + Paclitaxel/Carboplatin<br>Participants will receive bevacizumab matching placebo on Day 1 of each 3-week cycle in combination with paclitaxel and carboplatin for the first 6 treatment cycles (cycle length = 21 days). Participants will continue to receive bevacizumab matching placebo on Day 1 of each 3-week cycle until disease progression or unacceptable toxicity. | Drug: Carboplatin<br>* Carboplatin will be administered at area under the plasma concentration-time curve (AUC) 6.0 IV on Day 1 of each 3-week cycle, up to 6 cycles.<br>Drug: Paclitaxel<br>* Paclitaxel will be administered at 175 milligrams per square meter (mg/m^2) IV on Day 1 of each 3-week cycle, up to 6 cycles.<br>Drug: Placebo<br>* Bevacizumab matching placebo will be administered IV on Day 1 of each 3-week cycle until disease progression or unacceptable toxicity.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) as Assessed Using Response Evaluation Criteria in Solid Tumors Version 1.0 (RECIST v1.0) Criteria |  | Baseline up to death or disease progression, whichever occurs first (up to approximately 20 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) |  | Baseline up to death (up to approximately 35 months) | 
| Percentage of Participants Who are Alive at Year 1 |  | Year 1 | 
| Percentage of Participants With Objective Response of Complete Response (CR) or Partial Response (PR) as Assessed Using RECIST v1.0 Criteria |  | Baseline up to death or disease progression, whichever occurs first (up to approximately 35 months) | 
| Duration of Response as Assessed Using RECIST v1.0 Criteria |  | Baseline up to death or disease progression, whichever occurs first (up to approximately 35 months) | 
| Percentage of Participants With Adverse Events |  | From baseline up to approximately 35 months | 
| PFS as Assessed Using RECIST v1.0 Criteria in Subgroups Defined by Vascular Endothelial Growth Factor-A (VEGF-A) High/Low Level Expression at Baseline |  | Baseline up to death or disease progression, whichever occurs first (up to approximately 35 months) | 
| PFS as Assessed Using RECIST v1.0 Criteria in Subgroups Defined by Vascular Endothelial Growth Factor Receptor 2 (VEGFR-2) High/Low Level Expression at Baseline |  | Baseline up to death or disease progression, whichever occurs first (up to approximately 35 months) | 
| OS in Subgroups Defined by VEGF-A High/Low Level Expression at Baseline |  | Baseline up to death (up to approximately 35 months) | 
| OS in Subgroups Defined by VEGFR-2 High/Low Level Expression at Baseline |  | Baseline up to death (up to approximately 35 months) | 
| Percentage of Participants With Objective Response of CR or PR as Assessed Using RECIST v1.0 Criteria in Subgroups Defined by VEGF-A High/Low Level Expression at Baseline |  | Baseline up to death or disease progression, whichever occurs first (up to approximately 35 months) | 
| Percentage of Participants With Objective Response of CR or PR as Assessed Using RECIST v1.0 Criteria in Subgroups Defined by VEGFR-2 High/Low Level Expression at Baseline |  | Baseline up to death or disease progression, whichever occurs first (up to approximately 35 months) |