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

Non-Small Cell Lung Cancer Clinical Trial

Official title:

An Open Label Study to Assess the Effect of Avastin (Bevacizumab) Combined With First Line Paclitaxel-carboplatin or Second Line Tarceva (Erlotinib) on Progression-free Survival in Non-squamous Non-small Cell Lung Cancer Patients With Asymptomatic Untreated Brain Metastasis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00800202
• Other study ID #: ML21823
• Secondary ID: 2008-006504-33
• Status: Completed
• Phase: Phase 2
• First received: December 1, 2008
• Last updated: November 10, 2014
• Start date: April 2009
• Est. completion date: October 2012

Study information

• Verified date: November 2014
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: France:AFSSAPS
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 91
• Est. completion date: October 2012
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

Drug:
• bevacizumab [Avastin]
15mg/kg iv every 3 weeks
• carboplatin
AUC6 iv every 3 weeks for 6 cycles
• erlotinib [Tarceva]
150mg/day po
• paclitaxel
200mg/m2 iv every 3 weeks for 6 cycles

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Achieving Progression-Free Survival (PFS) Without Disease Progression or Death at 6 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.	6 months	No
Primary	Percentage of Participants With Disease Progression or Death	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.	Screening, 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	No
Primary	Time to Disease Progression or Death	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.	Screening, 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	No
Secondary	Percentage of Participants Who Died		Day 1 of Cycles 1, 2, 3, 4, 5, 6 and every 3 weeks up to 18 months or until death	No
Secondary	Probability of Being Alive at 12 and 18 Months		Months 12 and 18	No
Secondary	Time to 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.	Day 1 of Cycles 1, 2, 3, 4, 5, 6 and every 3 weeks up to 18 months or until death	No
Secondary	Percentage of Participants Achieving a Best Overall Response of Complete Response or Partial Response as Assessed by the Investigator Using RECIST	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.	Screening, 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	No