Clinical trial NCT01364012: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Non-Small Cell Lung Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2011-06-02
Enrollment: 276
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Progression-Free Survival (PFS) as Assessed Using Response Evaluation Criteria in Solid Tumors Version 1.0 (RECIST v1.0) Criteria
timeFrame: Baseline up to death or disease progression, whichever occurs first (up to approximately 20 months)
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Baseline up to death (up to approximately 35 months)
measure: Percentage of Participants Who are Alive at Year 1
timeFrame: Year 1
measure: Percentage of Participants With Objective Response of Complete Response (CR) or Partial Response (PR) as Assessed Using RECIST v1.0 Criteria
timeFrame: Baseline up to death or disease progression, whichever occurs first (up to approximately 35 months)
measure: Duration of Response as Assessed Using RECIST v1.0 Criteria
timeFrame: Baseline up to death or disease progression, whichever occurs first (up to approximately 35 months)
measure: Percentage of Participants With Adverse Events
timeFrame: From baseline up to approximately 35 months
measure: 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
timeFrame: Baseline up to death or disease progression, whichever occurs first (up to approximately 35 months)
measure: 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
timeFrame: Baseline up to death or disease progression, whichever occurs first (up to approximately 35 months)
measure: OS in Subgroups Defined by VEGF-A High/Low Level Expression at Baseline
timeFrame: Baseline up to death (up to approximately 35 months)
measure: OS in Subgroups Defined by VEGFR-2 High/Low Level Expression at Baseline
timeFrame: Baseline up to death (up to approximately 35 months)
measure: 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
timeFrame: Baseline up to death or disease progression, whichever occurs first (up to approximately 35 months)
measure: 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
timeFrame: Baseline up to death or disease progression, whichever occurs first (up to approximately 35 months)
Other outcomes:
Locations:
city: Beijing
country: China
facility: The Affiliated Hospital of Military Medical Sciences(The 307th Hospital of Chinese PLA)
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Beijing
country: China
facility: Beijing Hospital of Ministry of Health; Hematology
city: Beijing
country: China
facility: General Hospital of Chinese PLA; Department of Hematology
city: Beijing
country: China
facility: Beijing Chest Hospital; Oncology Department
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
city: Guangzhou
country: China
facility: Guangdong General Hospital
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangzhou Medical University
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
city: Nanjing
country: China
facility: Jiangsu Cancer Hospital
city: Nanning
country: China
facility: Guangxi Cancer Hospital of Guangxi Medical University
city: Shanghai
country: China
facility: Shanghai chest hospital
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital
city: Shantou
country: China
facility: Cancer Hospital of Shantou University Medical College
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.