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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Non-Squamous Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: bevacizumab [Avastin]
* Drug: cisplatin
* Drug: gemcitabine
* Drug: gemcitabine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: bevacizumab [Avastin]<br>* 7.5mg/kg iv on day 1 of each 3 week cycle<br>Drug: gemcitabine<br>* 1200mg/m2 on days 1-8 of each 3 week cycle<br>|
| Experimental: 2<br> | Drug: bevacizumab [Avastin]<br>* 7.5mg/kg iv on day 1 of each 3 week cycle<br>Drug: cisplatin<br>* 60mg/m2 on day 1 of each 3 week cycle<br>Drug: gemcitabine<br>* 1000mg/m2 on days 1-8 of each 3 week cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Alive and Without Progressive Disease at 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. | Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Disease Progression or Death | 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. | 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) | 
| Progression Free Survival (PFS) | 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. | 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) | 
| Percentage of Participants Alive at 12 Months After Randomization |  | 1 year | 
| Percentage of Participants Who Died |  | From randomization to death or end of the study (up to 53 months) | 
| Overall Survival (OS) | OS was defined as the interval between the date of randomization and death from any cause. OS was estimated using Kaplan Meier method. | From randomization to death or end of the study (up to 53 months) | 
| Percentage of Participants by Best Overall Response | 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. | 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) | 
| Percentage of Participants With an Objective Response | 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. | Cycle 3 Day 15, Cycle 6 Day 15 and at Month 6 | 
| Percentage of Participants With Disease Control | 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. | Cycle 3 Day 15, Cycle 6 Day 15 and at Month 6 | 
| Duration of Response (DoR) | 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. | 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) |