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

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

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.

Study Overview

• Status: Completed
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Bevacizumab; Drug: Carboplatin; Drug: Paclitaxel; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 276
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100142
    • Beijing Cancer Hospital
  • Beijing, China, 100071
    • The Affiliated Hospital of Military Medical Sciences(The 307th Hospital of Chinese PLA)
  • Beijing, China, 101149
    • Beijing Chest Hospital; Oncology Department
  • Beijing, China, 100853
    • General Hospital of Chinese PLA; Department of Hematology
  • Beijing, China, 100730
    • Beijing Hospital of Ministry of Health; Hematology
  • Changsha, China, 410011
    • The Second Xiangya Hospital of Central South University
  • Chengdu, China, 610041
    • West China Hospital, Sichuan University
  • Guangzhou, China, 510080
    • Guangdong General Hospital
  • Guangzhou, China, 510120
    • The First Affiliated Hospital of Guangzhou Medical University
  • Hangzhou, China, 310016
    • Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
  • Harbin, China, 150081
    • Harbin Medical University Cancer Hospital
  • Nanjing, China, 210009
    • Jiangsu Cancer Hospital
  • Nanning, China, 530021
    • Guangxi Cancer Hospital of Guangxi Medical University
  • Shanghai, China, 200030
    • Shanghai Chest Hospital
  • Shanghai, China, 200032
    • Fudan University Shanghai Cancer Center
  • Shanghai, China, 200433
    • Shanghai Pulmonary Hospital
  • Shantou, China, 515041
    • Cancer Hospital of Shantou University Medical College

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bevacizumab + Paclitaxel/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.	Drug: Bevacizumab; Bevacizumab will be administered at 15 mg/kg IV on Day 1 of each 3-week cycle until disease progression or unacceptable toxicity.; Other Names: Avastin; Drug: Carboplatin; 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.; Drug: Paclitaxel; 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.
Active Comparator: Placebo + Paclitaxel/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.	Drug: Carboplatin; 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.; Drug: Paclitaxel; 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.; Drug: Placebo; Bevacizumab matching placebo will be administered IV on Day 1 of each 3-week cycle until disease progression or unacceptable toxicity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Zhou C, Wu YL, Chen G, Liu X, Zhu Y, Lu S, Feng J, He J, Han B, Wang J, Jiang G, Hu C, Zhang H, Cheng G, Song X, Lu Y, Pan H, Zheng W, Yin AY. BEYOND: A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Phase III Study of First-Line Carboplatin/Paclitaxel Plus Bevacizumab or Placebo in Chinese Patients With Advanced or Recurrent Nonsquamous Non-Small-Cell Lung Cancer. J Clin Oncol. 2015 Jul 1;33(19):2197-204. doi: 10.1200/JCO.2014.59.4424. Epub 2015 May 26.

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2011
• Primary Completion (Actual): January 27, 2013
• Study Completion (Actual): August 17, 2017

Study Registration Dates

• First Submitted: May 27, 2011
• First Submitted That Met QC Criteria: May 31, 2011
• First Posted (Estimate): June 2, 2011

Study Record Updates

• Last Update Posted (Actual): February 5, 2018
• Last Update Submitted That Met QC Criteria: February 1, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Carboplatin; Paclitaxel; Bevacizumab
• Other Study ID Numbers: YO25404