A Study of Avastin (Bevacizumab) in Combination With Carboplatin-Based Chemotherapy in Patients With Advanced or Recurrent Non-Squamous Non-Small Cell Lung Cancer.

A Randomized, Open-label Study to Explore the Correlation of Biomarkers With Response Rate in Chemo-naive Patients With Advanced or Recurrent Non-squamous Non-small Cell Lung Cancer Who Receive Treatment With Avastin in Addition to Carboplatin-based Chemotherapy

This study will explore the correlation of biomarkers with response rate, and the overall efficacy and safety, of Avastin in combination with carboplatin-based chemotherapy in patients with advanced or recurrent non-squamous non-small cell lung cancer. Patients will be randomized to one of 2 groups, to receive either Avastin 7.5mg/kg iv on day 1 of each 3 week cycle, or Avastin 15mg/kg iv on day 1 of each 3 week cycle; all patients will also receive treatment with carboplatin and either gemcitabine or paclitaxel for a maximum of 6 cycles. The anticipated time on study treatment is until disease progression, and the target sample size is 100-500 individuals.

Study Overview

• Status: Completed
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: bevacizumab [Avastin]; Drug: bevacizumab [Avastin]; Drug: Carboplatin-based chemotherapy

• Study Type: Interventional
• Enrollment (Actual): 303
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • St. Leonards, New South Wales, Australia, 2065
  • South Australia
    • Adelaide, South Australia, Australia, 5041
    • Adelaide, South Australia, Australia, 5065
  • Victoria
    • Box Hill, Victoria, Australia, 3128
    • Fitzroy, Victoria, Australia, 3065
• Belgium
  • Antwerpen, Belgium, 2020
  • Liege, Belgium, 4000
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
  • Ontario
    • Toronto, Ontario, Canada, M5G2M9
• Czech Republic
  • Ostrava, Czech Republic, 708 52
  • Praha, Czech Republic, 180 01
• Denmark
  • Odense, Denmark, 5000
• France
  • Paris, France, 75970
  • Rouen, France, 76031
• Germany
  • Bad Berka, Germany, 99437
  • Grosshansdorf, Germany, 22927
  • Hamburg, Germany, 21075
  • Oldenburg, Germany, 26121
• Hong Kong
  • Hong Kong, Hong Kong
  • Hong Kong, Hong Kong, 852
• Hungary
  • Budapest, Hungary, 1529
  • Edeleny, Hungary, 3780
  • Sopron, Hungary, 9400
  • Szombathely, Hungary, 9700
  • Torokbalint, Hungary, 2045
• Italy
  • Milan, Italy, 20141
  • Milano, Italy, 20162
  • Orbassano, Italy, 10043
  • Roma, Italy, 00168
• Netherlands
  • Den Haag, Netherlands, 2504 LN
  • Enschede, Netherlands, 7500 KA
  • Hoorn, Netherlands, 1624 NP
  • Nieuwegein, Netherlands, 3435 CM
  • Rotterdam, Netherlands, 3075 EA
• Poland
  • Poznan, Poland, 60-569
  • Warszawa, Poland, 02-781
  • Zabrze, Poland, 41-843
• Russian Federation
  • Arkhangelsk, Russian Federation, 163045
  • Chelyabinsk, Russian Federation, 454 087
  • Kazan, Russian Federation, 420029
  • Kazan, Russian Federation, 420111
  • Krasnodar, Russian Federation, 350040
  • Krasnodar, Russian Federation, 350086
  • Moscow, Russian Federation, 105229
  • Moscow, Russian Federation, 115478
  • Saint-Petersburg, Russian Federation, 197758
  • St Petersburg, Russian Federation, 197089
• Spain
  • Sevilla, Spain, 41013
  • Valencia, Spain, 46010
  • Valencia, Spain, 46009
  • Vizcaya
    • Barakaldo, Vizcaya, Spain, 48903
• Taiwan
  • Changhua, Taiwan, 500
  • Taichung, Taiwan, 404
  • Taichung, Taiwan, 407
  • Taichung, Taiwan, 402
  • Taipei, Taiwan, 100
• United Kingdom
  • Aberdeen, United Kingdom, AB25 2ZN
  • Chelmsford, United Kingdom, CM1 7ET
  • London, United Kingdom, SE1 9RT

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:

• adult patients, >=18 years of age;
• locally advanced metastatic or recurrent non-squamous non-small cell lung cancer (NSCLC);
• >=1 measurable tumor lesion;
• ECOG performance status 0-1.

Exclusion Criteria:

• prior chemotherapy or treatment with another systemic anti-cancer agent;
• evidence of CNS metastases;
• history of grade 2 or higher hemoptysis;
• evidence of tumor invading or abutting major blood vessels;
• malignancies other than NSCLC within 5 years prior to randomization, other than adequately treated cancer in situ of cervix, basal or squamous cell skin cancer, localized prostate cancer or DCIS;
• clinically significant cardiovascular disease;
• current or recent use of aspirin (>325mg/day) or full dose anticoagulants or thrombolytic agents for therapeutic purposes.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: bevacizumab [Avastin]; 7.5mg/kg iv on day 1 of each 3 week cycle; Drug: bevacizumab [Avastin]; 15mg/kg iv on day 1 of each 3 week cycle; Drug: Carboplatin-based chemotherapy; As prescribed
Experimental: 2	Drug: bevacizumab [Avastin]; 7.5mg/kg iv on day 1 of each 3 week cycle; Drug: bevacizumab [Avastin]; 15mg/kg iv on day 1 of each 3 week cycle; Drug: Carboplatin-based chemotherapy; As prescribed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) by Dichotomized Baseline Plasma Marker Level	Overall response was analyzed and correlated within dichotomized (low- and high-level) baseline plasma biomarker (basic fibroblast growth factor [bFGF], E-selection, intracellular adhesion molecule [ICAM], placental growth factor [PlGF], vascular endothelial growth factor A [VEGF A], vascular endothelial growth factor receptor [VEGFR]-1, and VEGFR-2) subgroups: low-level equals (=) less than or equal to (≤) median baseline level, high-level=greater than (>) median baseline level. Per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.0 CR defined as disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. PR defined as greater than or equal to (≥)30 percent (%) decrease under baseline of the sum of the longest diameter (LD) of all target lesions. No unequivocal progression of non-target disease; no new lesions. Complete and partial responses must have been confirmed no less than 4 weeks after criteria for response were first met	Baseline, Day 21 of Cycles 2, 4, and 6 (Bv + chemo), Day 21 of Cycles 7, 8, 9, and 10 (Bv), Day 21 of every other cycle (Bv), and at disease progression.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival - Percentage of Participants With an Event	PFS was defined as the time between randomization and progressive disease (PD) according to RECIST criteria, or death due to any cause. PD was defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started. Disease progression was evaluated according to the RECIST using computed tomography (CT) scans, magnetic resonance imaging (MRI) scans, X-ray, bone scans, or clinical examination. Participants without an event were censored at the date of last follow up for progression. Participants with no post baseline follow-up for progression were censored at the day of randomization.	Baseline, Day 1, weekly to disease progression
Progression-Free Survival - Time to Event	PFS was defined as the time between randomization and disease progression or death due to any cause. Participants without an event were censored at the date of last follow up for progression. Participants with no post baseline follow-up for progression were censored at the day of randomization. Disease progression was evaluated according to the RECIST using CT scans, MRI scans, X-ray, bone scans, or clinical examination. Median PFS was estimated using the Kaplan-Meier method.	Baseline, Day 1, weekly to disease progression
Percentage of Participants With Objective Response	Percentage of participants with CR or PR according to RECIST criteria. Per RECIST v1.0: CR defined as disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. PR was defined as ≥30% decrease under baseline of the sum of the LD of all target lesions. No unequivocal progression of non-target disease. No new lesions. Complete and partial responses were confirmed no less than 4 weeks after the criteria for response were first met.	Baseline, Day 21 of Cycles 2, 4, and 6, Day 21 of Cycles 7, 8, 9, and 10, Day 21 of every other cycle, and at disease progression
Percentage of Participants With Measurable Disease at Baseline Who Achieved CR, PR, or Stable Disease (SD) for at Least 6 Weeks	Percentage of participants with measurable disease at baseline who on assessment achieved CR, PR, or SD according to RECIST. Per RECIST v1.0: CR defined as disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. PR was defined as ≥30% decrease under baseline of the sum of the LD of all target lesions. No unequivocal progression of non-target disease. No new lesions. SD defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum LD since start of treatment. Complete and partial responses must have been confirmed no less than 4 weeks after the criteria for response were first met. For participants with SD, follow-up assessments must have met the SD criteria at least once after study entry at a minimum interval of 6 weeks.	Baseline, Day 21 of Cycles 2, 4, and 6, Day 21 of Cycles 7, 8, 9, and 10, Day 21 of every other cycle, and at disease progression
Duration of Response - Percentage of Participants With an Event	Duration of response is defined as time in months from the first documentation of objective tumor response (CR or PR) to objective tumor progression or death due to any cause. Participants without an event (documented progression or death) were censored at the date of last follow-up for progression. Duration of response was only calculated for participants who had a confirmed objective tumor response (CR or PR).	Baseline, Day 21 of Cycles 2, 4, and 6, Day 21 of Cycles 7, 8, 9, and 10, Day 21 of every other cycle, and at disease progression
Duration of Response - Time to Event	The median time, in months, from the first documentation of objective tumor response (CR or PR) to objective tumor progression or death due to any cause. Participants without an event (documented progression or death) were censored at the date of last follow-up for progression. Duration of response was only calculated for participants who had a confirmed objective tumor response (CR or PR). Median Duration of Response was estimated using the Kaplan-Meier method.	Baseline, Day 21 of Cycles 2, 4, and 6 (Bv + chemo), Day 21 of Cycles 7, 8, 9, and 10 (Bv), Day 21 of every other cycle (Bv), and at disease progression.
Overall Survival - Percentage of Participants With an Event	Overall survival was defined as the time between randomization and death due to any cause. Participants without an event were censored at the last time they were known to be alive. Overall Survival was estimated using the Kaplan-Meier method.	Baseline, weekly to 28 days after last dose of study treatment, every 8 weeks thereafter to death due to any cause
Overall Survival - Time to Event	Overall survival was defined as the time between randomization and death due to any cause. Participants without an event were censored at the last time they were known to be alive. Overall Survival was estimated using the Kaplan-Meier method.	Baseline, weekly to death due to any cause, or to end of study

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: June 17, 2008
• First Submitted That Met QC Criteria: June 17, 2008
• First Posted (Estimate): June 18, 2008

Study Record Updates

• Last Update Posted (Estimate): September 25, 2014
• Last Update Submitted That Met QC Criteria: September 23, 2014
• Last Verified: September 1, 2014

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; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Carboplatin; Bevacizumab
• Other Study ID Numbers: BO21015; 2008-000662-23