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

• ClinicalTrials.gov Identifier: NCT01364012
• Recruitment Status: Completed
• First Posted: June 2, 2011
• Last Update Posted: February 5, 2018
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: May 27, 2011
• First Posted Date: June 2, 2011
• Last Update Posted Date: February 5, 2018
• Actual Study Start Date: May 23, 2011
• Actual Primary Completion Date: January 27, 2013 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: July 26, 2017): Progression-Free Survival (PFS) as Assessed Using Response Evaluation Criteria in Solid Tumors Version 1.0 (RECIST v1.0) Criteria [ Time Frame: Baseline up to death or disease progression, whichever occurs first (up to approximately 20 months) ]
• Original Primary Outcome Measures (submitted: May 31, 2011): Progression-free survival (PFS), tumour assessments according to RECIST criteria [ Time Frame: approximately 24 months ]

Current Secondary Outcome Measures (submitted: July 26, 2017)

• Overall Survival (OS) [ Time Frame: Baseline up to death (up to approximately 35 months) ]
• Percentage of Participants Who are Alive at Year 1 [ Time Frame: Year 1 ]
• Percentage of Participants With Objective Response of Complete Response (CR) or Partial Response (PR) as Assessed Using RECIST v1.0 Criteria [ Time Frame: 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 [ Time Frame: Baseline up to death or disease progression, whichever occurs first (up to approximately 35 months) ]
• Percentage of Participants With Adverse Events [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Baseline up to death (up to approximately 35 months) ]
• OS in Subgroups Defined by VEGFR-2 High/Low Level Expression at Baseline [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Baseline up to death or disease progression, whichever occurs first (up to approximately 35 months) ]

Original Secondary Outcome Measures (submitted: May 31, 2011)

• Overall survival (OS) [ Time Frame: approximately 48 months ]
• 1-year survival rate [ Time Frame: approximately 30 months ]
• Overall response rate (ORR): complete response + partial response [ Time Frame: approximately 24 months ]
• Duration of response [ Time Frame: approximately 24 months ]
• Safety: Incidence of adverse events [ Time Frame: approximately 48 months ]
• Correlation of baseline vascular endothelial growth factor (VEGF) plasma levels with clinical outcome (PFS/OS/ORR) [ Time Frame: approximately 48 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Non-Small Cell Lung Cancer

Intervention

• 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 Name: 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.
• Drug: Placebo
  Bevacizumab matching placebo will be administered IV on Day 1 of each 3-week cycle until disease progression or unacceptable toxicity.

Study Arms

• 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.
  Interventions:

  • Drug: Bevacizumab
  • Drug: Carboplatin
  • Drug: Paclitaxel
• 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.
  Interventions:

  • Drug: Carboplatin
  • Drug: Paclitaxel
  • Drug: Placebo

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 23, 2015): 276
• Original Estimated Enrollment (submitted: May 31, 2011): 270
• Actual Study Completion Date: August 17, 2017
• Actual Primary Completion Date: January 27, 2013 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT01364012
• Other Study ID Numbers: YO25404
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Hoffmann-La Roche
• Original Responsible Party: Disclosures Group, Hoffmann-La Roche
• Current Study Sponsor: Hoffmann-La Roche
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: February 2018