A Study of Avastin (Bevacizumab) + Xeloda (Capecitabine)as Maintenance Therapy in Patients With HER2-Negative Metastatic Breast Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00929240
First received: June 16, 2009
Last updated: March 2, 2015
Last verified: March 2015
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Drug: bevacizumab [Avastin]
Drug: capecitabine [Xeloda]
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Study of the Effect of Maintenance Therapy With Bevacizumab + Capecitabine Versus Bevacizumab Alone on Progression-free Survival in Patients With HER2-negative Metastatic Breast Cancer That Has Not Progressed During First-line Docetaxel Plus Bevacizumab Therapy

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants With Disease Progression or Death (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 ] [ Designated as safety issue: No ]
    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.

  • Progression Free Survival (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 ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • Percentage of Participants With Best Overall Confirmed Objective Response of CR or PR Per RECIST 1.0 (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 ] [ Designated as safety issue: No ]
    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).

  • Percentage of Participants With Clinical Benefit (CR, PR and SD) Per RECIST 1.0 (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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
  • Overall Survival (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 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Expected to Be Alive After 1 and 2 Years on Treatment (Maintenance Phase Data Cutoff October 4, 2013) [ Time Frame: Years 1 and 2 ] [ Designated as safety issue: No ]
    Probability of being alive after 1 and 2 years on treatment with 95% CIs was calculated using Kaplan Meier approach with LOGLOG transformation.

  • Percentage Of Participants With PD or Death Due to PD (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 ] [ Designated as safety issue: No ]
    PD was defined per RECIST 1.0 as 20% increase in the sum of the longest diameter of target lesions.

  • Time To Progression (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 ] [ Designated as safety issue: No ]
    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.

  • 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) [ Time Frame: Baseline, Randomization and Cycles 3, 6, 9 and 12 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Best Overall Confirmed Objective Response of CR or PR Per RECIST 1.0 (Initial Treatment Phase) [ Time Frame: Screening and at the end of every third cycle until randomization for an average of 18 weeks ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Clinical Benefit (CR, PR and SD) Per RECIST 1.0 (Initial Treatment Phase) [ Time Frame: Screening and at the end of every third cycle until randomization for an average of 18 weeks ] [ Designated as safety issue: No ]
    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.


Enrollment: 287
Study Start Date: July 2009
Study Completion Date: June 2014
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Avastin (bevacizumab) Drug: bevacizumab [Avastin]
15 mg/kg iv on day 1 of each 3 week cycle (maintenance phase)
Experimental: Avastin (bevacizumab) + Xeloda (capecitabine) Drug: bevacizumab [Avastin]
15 mg/kg iv on day 1 of each 3 week cycle (maintenance phase)
Drug: capecitabine [Xeloda]
1000 mg/m2 po bid on days 1-14 of each 3 week cycle (maintenance phase)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • adult patients, >=18 years of age;
  • HER2-negative metastatic breast cancer
  • candidates for taxane-based chemotherapy;
  • ECOG performance status of 0 or 1.

Exclusion Criteria:

  • previous chemotherapy for metastatic breast cancer;
  • prior adjuvant/neo-adjuvant chemotherapy within 6 months prior to study;
  • prior radiotherapy for treatment of metastatic disease;
  • chronic daily treatment with aspirin (325 mg/day) or clopidogrel(>75mg/day).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00929240

  Show 63 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided by Hoffmann-La Roche

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00929240     History of Changes
Other Study ID Numbers: MO22223, 2008-006872-31
Study First Received: June 16, 2009
Results First Received: February 5, 2015
Last Updated: March 2, 2015
Health Authority: Spain: Ministry of Health

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Bevacizumab
Capecitabine
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on July 01, 2015