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

Hoffmann-La Roche86 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Non-Squamous Non-Small Cell Lung Cancer

Interventions

Eligibility

Sex: ALLMin age: 70 Years

Medical Language ↔ Plain English

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.

Locations (26)

Unnamed facility

Rionero in Vulture, Basilicate, Italy

Unnamed facility

Catanzaro, Calabria, Italy

Unnamed facility

Avellino, Campania, Italy

Unnamed facility

Naples, Campania, Italy

Unnamed facility

Bologna, Emilia-Romagna, Italy

Unnamed facility

Aviano, Friuli Venezia Giulia, Italy

Unnamed facility

Udine, Friuli Venezia Giulia, Italy

Unnamed facility

Rome, Lazio, Italy

Unnamed facility

Rome, Lazio, Italy

Unnamed facility

Rome, Lazio, Italy

...and 16 more locations

Outcomes

Primary Outcomes

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.

Time frame: Month 6

Secondary Outcomes

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.

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)

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.

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)

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)

OS was defined as the interval between the date of randomization and death from any cause. OS was estimated using Kaplan Meier method.

Time frame: 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.

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)

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.

Time frame: 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.

Time frame: 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.

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)