This randomized study will compare maintenance therapy with Avastin (bevacizumab) + Xeloda (capecitabine) versus Avastin alone, in patients with HER2-negative metastatic breast cancer who have not progressed during first-line therapy with docetaxel + Avastin. Eligible patients will receive up to 6 x 3 week cycles of treatment with Avastin (15 mg/mg IV on Day 1 of each cycle) + docetaxel (75-100 mg/m2 IV on Day 1 of each cycle). Those patients who do not progress will be randomized to 3 week cycles of either a) Avastin (15 mg/kg IV on Day 1 of each cycle) + Xeloda (1000 mg/m2 po bid on Days 1-14 of each cycle) or b) Avastin alone. Study treatment will continue until disease progression, unacceptable toxicity, patient request for withdrawal or end of study, and the target sample size is 100-500 individuals.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
287
15 mg/kg iv on day 1 of each 3 week cycle (maintenance phase)
1000 mg/m2 po bid on days 1-14 of each 3 week cycle (maintenance phase)
Unnamed facility
Fortaleza, Ceará, Brazil
Unnamed facility
Belo Horizonte, Minas Gerais, Brazil
Unnamed facility
Rio de Janeiro, Rio de Janeiro, Brazil
Unnamed facility
Ijuí, Rio Grande do Sul, Brazil
Unnamed facility
Porto Alegre, Rio Grande do Sul, Brazil
Unnamed facility
Percentage of Participants With Disease Progression or Death (Maintenance Phase Data Cutoff October 4, 2013)
Progression Free Survival (PFS) was defined as the time from first study drug dosing (during the maintenance treatment phase) to the first documented disease progression or death, whichever occurred first. Progression was based on tumor assessment made by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST). Progressive Disease (PD) was defined as a 20 percent (%) or greater increase in the sum of the Longest Diameter (LD) of the target lesions taking as reference the smallest sum LD recorded or appearance of new lesions.
Time frame: Randomization, at the end of every third cycle (every 9 weeks) until the end of maintenance phase and every 3 months until disease progression or death until data cutoff on October 4, 2013, up to 4 years
Progression Free Survival (Maintenance Phase Data Cutoff October 4, 2013)
PFS was defined as the time from first study drug dosing to the first documented disease progression or death, whichever occurred first.Time to progression was defined as the time from randomization to the first documented disease progression defined per RECIST 1.0 criteria. Participants without an event at data cut-off or who were withdrawn from the study without documented progression were censored at the date of the last tumor assessment when the participant was known to be progression free. Participants who took other non-protocol anti-cancer drugs while being on study medication, and who were still event free were censored on the date of first dose of the anti-cancer drug. Participants without post-randomization tumor assessments but alive were censored at the time of randomization. Participants without post-randomization assessments, who died after randomization were considered to have the PFS event at date of death. Kaplan-Meier estimation was used for median time to PFS
Time frame: Randomization, at the end of every third cycle (every 9 weeks) until the end of maintenance phase and every 3 months until disease progression or death until data cutoff on October 4, 2013, up to 4 years
Percentage of Participants With Best Overall Confirmed Objective Response of CR or PR Per RECIST 1.0 (Maintenance Phase Data Cutoff October 4, 2013)
Objective Response was determined by the investigator using modified RECIST criteria, Version 1.0. An objective response was a complete or partial overall confirmed response as determined by investigators. CR was defined as complete disappearance of all target and non-target lesions and no new lesions. PR was defined as greater than or equal to (≥) 30 % decrease in the sum of appropriate diameters of all target measurable lesions, no progress in the non-measurable disease, and no new lesions. Progressive disease (PD) was defined as 20% increase in the sum of the longest diameter of target lesions and SD was defined as small changes that do not meet above criteria. Pearson-Clopper one-sample method was used for Confidence intervals (CIs).
Time frame: Randomization, at the end of every third cycle (every 9 weeks) until the end of maintenance phase and every 3 months until disease progression or death until data cutoff on October 4, 2013, up to 4 years
Percentage of Participants With Clinical Benefit (CR, PR and SD) Per RECIST 1.0 (Data Cutoff October 4, 2013)
CR was defined as complete disappearance of all target and non-target lesions and no new lesions. PR was defined as ≥ 30 % decrease in the sum of appropriate diameters of all target measurable lesions, no progress in the non-measurable disease, and no new lesions. SD was defined as small changes that do not meet above criteria.
Time frame: Randomization, at the end of every third cycle (every 9 weeks) until the end of maintenance phase and every 3 months until disease progression or death until data cutoff on October 4, 2013, up to 4 years
Percentage of Participants Who Died (Maintenance Phase Data Cutoff October 4, 2013)
Time frame: Randomization, at the end of every third cycle (every 9 weeks) until the end of maintenance phase and every 3 months until disease progression or death until data cutoff on October 4, 2013, up to 4 years
Overall Survival (Maintenance Phase Data Cutoff October 4, 2013)
Duration of Overall Survival (OS) was defined as the time from randomization to death of any cause. The OS data for participants for whom no death was captured in the clinical database were censored at the last time they were known to be alive. Kaplan Meier estimation was used to determine OS.
Time frame: Randomization, at the end of every third cycle (every 9 weeks) until the end of maintenance phase and every 3 months until disease progression or death until data cutoff on October 4, 2013, up to 4 years
Percentage of Participants Expected to Be Alive After 1 and 2 Years on Treatment (Maintenance Phase Data Cutoff October 4, 2013)
Probability of being alive after 1 and 2 years on treatment with 95% CIs was calculated using Kaplan Meier approach with LOGLOG transformation.
Time frame: Years 1 and 2
Percentage Of Participants With PD or Death Due to PD (Maintenance Phase Data Cutoff October 4, 2013)
PD was defined per RECIST 1.0 as 20% increase in the sum of the longest diameter of target lesions.
Time frame: Randomization, at the end of every third cycle (every 9 weeks) until the end of maintenance phase and every 3 months until disease progression or death until data cutoff on October 4, 2013
Time To Progression (Maintenance Phase Data Cutoff October 4, 2013)
Time to Progression was defined as the time from randomization to the first documented disease progression (using investigator assessments of disease progression by RECIST 1.0). PD was defined as 20% increase in the sum of the longest diameter of target lesions.
Time frame: Randomization, at the end of every third cycle (every 9 weeks) until the end of maintenance phase and every 3 months until disease progression or death until data cutoff on October 4, 2013
Quality of Life Assessed As Change From Baseline in Global Health Status Using The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - 30 (EORTC QLQ - C30) (Maintenance Phase Data Cutoff October 4, 2013)
The EORTC QLQ-C30 incorporates 9 multi-item scales: 5 functional scales (physical, role, cognitive, emotional, and social); 9 symptom scales (fatigue, pain, nausea and vomiting, dyspnoea, insomnia, appetite loss, constipation, diarrhea and financial difficulties); and a global health and quality-of-life scale. Most questions used 4 point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale (1 'very poor' to 7 'Excellent'). Scores were averaged and transformed to 0-100 scale; higher score=better level of functioning or greater degree of symptoms. The change in global health status was determined to be the difference in values at baseline and each specific visit. The term ''baseline'' refers to the time of randomization to the maintenance phase.
Time frame: Baseline, Randomization and Cycles 3, 6, 9 and 12
Percentage of Participants With Best Overall Confirmed Objective Response of CR or PR Per RECIST 1.0 (Initial Treatment Phase)
Objective Response was determined by the investigator using RECIST criteria, Version 1.0. An objective response was a complete or partial overall confirmed response as determined by investigators. CR was defined as complete disappearance of all target and non-target lesions and no new lesions. PR was defined as ≥ 30% decrease in the sum of appropriate diameters of all target measurable lesions, no progress in the non-measurable disease, and no new lesions. Pearson-Clopper one-sample method was used for CI.
Time frame: Screening and at the end of every third cycle until randomization for an average of 18 weeks
Percentage of Participants With Clinical Benefit (CR, PR and SD) Per RECIST 1.0 (Initial Treatment Phase)
CR was defined as complete disappearance of all target and non-target lesions and no new lesions. PR was defined as ≥30% decrease in the sum of appropriate diameters of all target measurable lesions, no progress in the non-measurable disease, and no new lesions. SD was defined as small changes that do not meet above criteria.
Time frame: Screening and at the end of every third cycle until randomization for an average of 18 weeks
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Jaú, São Paulo, Brazil
Unnamed facility
Santo André, São Paulo, Brazil
Unnamed facility
São Paulo, São Paulo, Brazil
Unnamed facility
São Paulo, São Paulo, Brazil
Unnamed facility
Beijing, China
...and 53 more locations