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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01077713
First received: February 9, 2010
Last updated: September 9, 2015
Last verified: September 2015
  Purpose
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.

Condition Intervention Phase
Non-Squamous Non-Small Cell Lung Cancer
Drug: bevacizumab [Avastin]
Drug: cisplatin
Drug: gemcitabine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants Alive and Without Progressive Disease at Month 6 [ Time Frame: Month 6 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • Percentage of Participants Who Died [ Time Frame: From randomization to death or end of the study (up to 53 months) ] [ Designated as safety issue: No ]
  • Overall Survival (OS) [ Time Frame: From randomization to death or end of the study (up to 53 months) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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.


Enrollment: 86
Study Start Date: February 2010
Study Completion Date: July 2014
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: bevacizumab [Avastin]
7.5mg/kg iv on day 1 of each 3 week cycle
Drug: gemcitabine
1200mg/m2 on days 1-8 of each 3 week cycle
Experimental: 2 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
1000mg/m2 on days 1-8 of each 3 week cycle

  Eligibility

Ages Eligible for Study:   70 Years and older   (Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01077713

Locations
Italy
Rionero in Vulture, Basilicata, Italy, 85028
Catanzaro, Calabria, Italy, 88100
Avellino, Campania, Italy, 83100
Napoli, Campania, Italy, 80131
Bologna, Emilia-Romagna, Italy, 40139
Aviano, Friuli-Venezia Giulia, Italy, 33081
Udine, Friuli-Venezia Giulia, Italy, 33100
Roma, Lazio, Italy, 00128
Roma, Lazio, Italy, 00189
Roma, Lazio, Italy, 00152
Viterbo, Lazio, Italy, 01100
Genova, Liguria, Italy, 16149
Bergamo, Lombardia, Italy, 24128
Milano, Lombardia, Italy, 20142
Monza, Lombardia, Italy, 20052
Rho, Lombardia, Italy, 20017
Sondalo, Lombardia, Italy, 23039
Sondrio, Lombardia, Italy, 23100
Ancona, Marche, Italy, 60121
Pesaro, Marche, Italy, 61122
Novara, Piemonte, Italy, 28100
Catania, Sicilia, Italy, 95100
Lido Di Camaiore, Toscana, Italy, 55043
Perugia, Umbria, Italy, 06156
Mirano, Veneto, Italy, 30035
Padova, Veneto, Italy, 35128
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01077713     History of Changes
Other Study ID Numbers: ML21868  2008-008739-27 
Study First Received: February 9, 2010
Results First Received: September 9, 2015
Last Updated: September 9, 2015
Health Authority: Italy: Ministry of Health

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Gemcitabine
Cisplatin
Bevacizumab
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on July 24, 2016