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
- Conditions
- Non-Small Cell Lung Cancer
- Interventions
- Registration Number
- NCT01364012
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 276
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Bevacizumab + Paclitaxel/Carboplatin Carboplatin 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. Placebo + Paclitaxel/Carboplatin Placebo 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. Bevacizumab + Paclitaxel/Carboplatin Bevacizumab 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. Bevacizumab + Paclitaxel/Carboplatin Paclitaxel 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. Placebo + Paclitaxel/Carboplatin Carboplatin 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. Placebo + Paclitaxel/Carboplatin Paclitaxel 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.
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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) 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) Overall Survival (OS) Baseline up to death (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) 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)
Trial Locations
- Locations (17)
Beijing Hospital of Ministry of Health; Hematology
🇨🇳Beijing, China
General Hospital of Chinese PLA; Department of Hematology
🇨🇳Beijing, China
Beijing Chest Hospital; Oncology Department
🇨🇳Beijing, China
The Second Xiangya Hospital of Central South University
🇨🇳Changsha, China
The Affiliated Hospital of Military Medical Sciences(The 307th Hospital of Chinese PLA)
🇨🇳Beijing, China
Beijing Cancer Hospital
🇨🇳Beijing, China
West China Hospital, Sichuan University
🇨🇳Chengdu, China
Guangdong General Hospital
🇨🇳Guangzhou, China
The First Affiliated Hospital of Guangzhou Medical University
🇨🇳Guangzhou, China
Harbin Medical University Cancer Hospital
🇨🇳Harbin, China
Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
🇨🇳Hangzhou, China
Guangxi Cancer Hospital of Guangxi Medical University
🇨🇳Nanning, China
Shanghai chest hospital
🇨🇳Shanghai, China
Shanghai Pulmonary Hospital
🇨🇳Shanghai, China
Cancer Hospital of Shantou University Medical College
🇨🇳Shantou, China
Fudan University Shanghai Cancer Center
🇨🇳Shanghai, China
Jiangsu Cancer Hospital
🇨🇳Nanjing, China