A Study of Avastin (Bevacizumab) in Combination With Gemcitabine With or Without Cisplatin in First-Line Treatment of Elderly Patients With Non-Small Cell Lung Cancer

• ClinicalTrials.gov Identifier: NCT01077713
• Recruitment Status: Completed
• First Posted: March 1, 2010
• Results First Posted: October 8, 2015
• Last Update Posted: October 8, 2015
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: February 9, 2010
• First Posted Date: March 1, 2010
• Results First Submitted Date: September 9, 2015
• Results First Posted Date: October 8, 2015
• Last Update Posted Date: October 8, 2015
• Study Start Date: February 2010
• Actual Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 9, 2015)

Percentage of Participants Alive and Without Progressive Disease at Month 6 [ Time Frame: Month 6 ]

Disease progression was assessed according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1 (v 1.1). Disease progression was defined at least a 20% increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 millimeter (mm), progression of existing non-target lesions, or presence of new lesions.

• Original Primary Outcome Measures (submitted: February 26, 2010): Progression-free survival [ Time Frame: 6 months ]

Current Secondary Outcome Measures (submitted: September 9, 2015)

• Percentage of Participants With Disease Progression or Death [ Time Frame: Baseline; Day 15 of Cycles 3 and 6; Month 6 and then every 3 months until disease progression, death, or consent withdrawal (up to 53 months) ]
  Disease progression was assessed according to RECIST criteria v1.1. Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions.
• Progression Free Survival (PFS) [ Time Frame: Baseline; Day 15 of Cycles 3 and 6; Month 6 and then every 3 months until disease progression, death, or consent withdrawal (up to 53 months) ]
  PFS was defined as the interval between the date of randomization and the first documentation of progressive disease or death from any cause. Disease progression was assessed according to RECIST criteria v 1.1. Disease progression was defined at least 20% increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. PFS was estimated using Kaplan Meier method.
• Percentage of Participants Alive at 12 Months After Randomization [ Time Frame: 1 year ]
• Percentage of Participants Who Died [ Time Frame: From randomization to death or end of the study (up to 53 months) ]
• Overall Survival (OS) [ Time Frame: From randomization to death or end of the study (up to 53 months) ]
  OS was defined as the interval between the date of randomization and death from any cause. OS was estimated using Kaplan Meier method.
• Percentage of Participants by Best Overall Response [ Time Frame: Baseline; Day 15 of Cycles 3 and 6; Month 6 and then every 3 months until disease progression, death or consent withdrawal (up to 53 months) ]
  Best overall response was defined as the best response recorded from the start of the treatment until disease progression/recurrence, assessed according to RECIST criteria v 1.1. Complete Response (CR): disappearance of all target and non-target lesions and no new lesions, all pathological lymph nodes must have decreased to less than (<) 10 millimeter (mm) in short axis; Partial Response (PR): at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters), no progression in non-target lesion, and no new lesions; Progressive Disease (PD): at least 20% increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions; Stable Disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
• Percentage of Participants With an Objective Response [ Time Frame: Cycle 3 Day 15, Cycle 6 Day 15 and at Month 6 ]
  Objective response was defined as having a CR or PR according to a RECIST criteria v 1.1. CR was defined as disappearance of all target and non-target lesions and no new lesions, all pathological lymph nodes must have decreased to <10 mm in short axis. PR was defined as at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters), no progression in non-target lesions, and no new lesions.
• Percentage of Participants With Disease Control [ Time Frame: Cycle 3 Day 15, Cycle 6 Day 15 and at Month 6 ]
  Disease control was defined as having CR/PR/SD as per RECIST criteria v 1.1. CR was defined as disappearance of all target and non-target lesions and no new lesions, all pathological lymph nodes must have decreased to <10 mm in short axis. PR was defined as at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters), no progression in non-target lesions, and no new lesions. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD was defined as at least 20% increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions.
• Duration of Response (DoR) [ Time Frame: Baseline; Day 15 of Cycles 3 and 6; Month 6 and then every 3 months until disease progression, death or consent withdrawal (up to 53 months) ]
  DoR was defined for participants who had achieved an objective response (CR/PR) (whichever status was recorded first) as the time period from first documentation of a response to the date of first occurrence of investigator documented disease progression or death. CR was defined as disappearance of all target and non-target lesions and no new lesions, all pathological lymph nodes must have decreased to <10 mm in short axis. PR was defined as at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters), no progression in non-target lesions, and no new lesions. Disease progression was defined as increase by at least 20% in the sum of the longest diameters of each target lesion, taking as a reference the smallest sum of the longest diameters or appearance of one or more new lesions. DoR was estimated using Kaplan Meier method.

Original Secondary Outcome Measures (submitted: February 26, 2010)

• Overall survival [ Time Frame: 6 months ]
• Objective response rate [ Time Frame: Tumor assessments at each clinic visit for 6 months ]
• Duration of response [ Time Frame: Tumor assessments at each clinic visit for 6 months ]
• Adverse events [ Time Frame: Throughout study for 6 months ]
• Laboratory parameters [ Time Frame: At each clinic visit for 6 months ]

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

Descriptive Information

• Brief Title: A Study of Avastin (Bevacizumab) in Combination With Gemcitabine With or Without Cisplatin in First-Line Treatment of Elderly Patients With Non-Small Cell Lung Cancer
• Official Title: Randomised Phase II Trial of Bevacizumab (AVASTIN®) in Combination With Gemcitabine or Attenuated Doses of Cisplatin and Gemcitabine as First-line Treatment of Elderly Patients With Advanced Non-squamous Non-small Cell Lung Cancer - EAGLES
• Brief Summary: This 2 arm study will evaluate the efficacy and safety of Avastin + gemcitabine, and Avastin + gemcitabine + attenuated doses of cisplatin, as first line treatment in elderly patients with non-squamous non-small cell lung cancer. Patients will be randomised to receive either Avastin 7.5mg/kg iv on day 1 + gemcitabine 1200mg/m2 on days 1-8 of each 3 week cycle, or Avastin 7.5mg/kg iv on day 1 + cisplatin 60mg/m2 on day 1 + gemcitabine 1000mg/m2 on days 1-8 of each 3 week cycle. After 6 cycles of combination therapy, all patients will continue to receive Avastin monotherapy. The anticipated time on study treatment is until disease progression, and the target sample size is <100 individuals.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non-Squamous Non-Small Cell Lung Cancer

Intervention

• Drug: bevacizumab [Avastin]
  7.5mg/kg iv on day 1 of each 3 week cycle
• Drug: cisplatin
  60mg/m2 on day 1 of each 3 week cycle
• Drug: gemcitabine
  1200mg/m2 on days 1-8 of each 3 week cycle
• Drug: gemcitabine
  1000mg/m2 on days 1-8 of each 3 week cycle

Study Arms

• Experimental: 1
  Interventions:

  • Drug: bevacizumab [Avastin]
  • Drug: gemcitabine
• Experimental: 2
  Interventions:

  • Drug: bevacizumab [Avastin]
  • Drug: cisplatin
  • Drug: gemcitabine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 11, 2013): 86
• Original Estimated Enrollment (submitted: February 26, 2010): 78
• Actual Study Completion Date: July 2014
• Actual Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• adult patients, >=70 years of age;
• inoperable, locally advanced, metastatic non-squamous non-small cell lung cancer;
• >=1 measurable lesion;
• ECOG performance status 0-1.

Exclusion Criteria:

• neoadjuvant/adjuvant chemotherapy within 6 months prior to enrollment;
• radical radiotherapy with curative intent within 28 days prior to enrollment;
• history of >=grade 2 hemoptysis in 3 months prior to enrollment;
• evidence of CNS metastases;
• current or recent (within 10 days of first dose of Avastin)use of aspirin (>325 mg/day)or full dose anticoagulants or thrombolytic agents for therapeutic purposes.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 70 Years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Italy

Administrative Information

• NCT Number: NCT01077713
• Other Study ID Numbers: ML21868; 2008-008739-27
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Hoffmann-La Roche
• Study Sponsor: Hoffmann-La Roche
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: September 2015