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A Study of Avastin (Bevacizumab) in Patients With Non-Squamous Non-Small Cell Lung Cancer With Asymptomatic Untreated Brain Metastasis

Phase 2
Completed
Conditions
Non-Small Cell Lung Cancer
Interventions
Registration Number
NCT00800202
Lead Sponsor
Hoffmann-La Roche
Brief Summary

This study will assess the efficacy and safety of Avastin combined with first li ne paclitaxel-carboplatin (cohort 1) or second line Tarceva (cohort 2) in patien ts with non-squamous non-small cell lung cancer with asymptomatic untreated brai n metastasis. Two cohorts of patients will be studied; the first will receive Av astin 15mg/kg iv every 3 weeks combined with first line paclitaxel 200mg/m2 iv p lus carboplatin AUC6 iv every 3 weeks for a maximum of 6 cycles, and the second cohort will receive Avastin 15mg/kg iv every 3 weeks combined with second line T arceva 150mg/kg po.The anticipated time on study treatment is until disease prog ression, and the target sample size is 100-500 individuals.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
91
Inclusion Criteria
  • adult patients, >=18 years of age;
  • stage IV non-squamous non-small cell lung cancer;
  • asymptomatic, untreated brain metastasis;
  • ECOG performance status 0-1.
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Exclusion Criteria
  • previous treatment for brain metastasis;
  • history of migraine or epilepsy;
  • previous treatment with angiogenesis inhibitors;
  • for cohort 2, previous first line treatment with Avastin or Tarceva;
  • current or recent use of aspirin (>325mg/day) or full-dose anticoagulants or thrombolytic agent for therapeutic purposes.
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
1bevacizumab [Avastin]-
2bevacizumab [Avastin]-
2erlotinib [Tarceva]-
1carboplatin-
1paclitaxel-
Primary Outcome Measures
NameTimeMethod
Percentage of Participants Achieving Progression-Free Survival (PFS) Without Disease Progression or Death at 6 Months6 months

Tumor progression was defined according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1 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, reported since the start of treatment, or appearance of one or more new lesions. PFS (investigator assessed) was defined as the time between the first dose of study treatment and the first event of progression or death by any cause. Participants without an event were censored the last time they were known to be progression free. PFS was analyzed using the Kaplan-Meier method in each treatment arm.

Percentage of Participants With Disease Progression or DeathScreening, Day 1 of Cycles 3 and 5 and every 2 cycles until end of treatment visit or disease progression or death up to 18 months after enrollment of last participant

Tumor progression was defined according to the RECIST criteria 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, reported since the start of treatment, or appearance of one or more new lesions. PFS (investigator assessed) was defined as the time between the first dose of study treatment and the first event of progression or death by any cause. Participants without an event were censored the last time they were known to be progression free. PFS was analyzed using the Kaplan-Meier method in each treatment arm.

Time to Disease Progression or DeathScreening, Day 1 of Cycles 3 and 5 and every 2 cycles until end of treatment visit or disease progression or death up to 18 months after enrollment of last participant

Tumor 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, reported since the start of treatment, or appearance of one or more new lesions. Time to event was determined as the number of months between the first dose of study treatment and the first event of progression or death by any cause. PFS was analyzed using the Kaplan-Meier method in each treatment arm.

Secondary Outcome Measures
NameTimeMethod
Probability of Being Alive at 12 and 18 MonthsMonths 12 and 18
Time to DeathDay 1 of Cycles 1, 2, 3, 4, 5, 6 and every 3 weeks up to 18 months or until death

Time to death was determined as the number of months between the first dose of study treatment and the event of death by any cause. Overall survival was analyzed using the Kaplan-Meier method.

Percentage of Participants Who DiedDay 1 of Cycles 1, 2, 3, 4, 5, 6 and every 3 weeks up to 18 months or until death
Percentage of Participants Achieving a Best Overall Response of Complete Response or Partial Response as Assessed by the Investigator Using RECISTScreening, Day 1 of Cycles 3 and 5 and every 2 cycles until end of treatment visit or disease progression or death up to 18 months after enrollment of last participant

Overall response defined as best response according to RECIST recorded from date of randomization until disease progression or recurrence. Complete Response (CR): disappearance of all target lesions; Partial response (PR): reduction by at least 30 percent (%) of sum of the longest diameters of each target lesion, taking initial sum of longest diameters as a reference. Participants with a missing response were considered non-responders. 95% CI for one sample binomial using Pearson-Clopper method.

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