Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00929240
Recruitment Status : Completed
First Posted : June 26, 2009
Results First Posted : March 3, 2015
Last Update Posted : March 3, 2015
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE June 16, 2009
First Posted Date  ICMJE June 26, 2009
Results First Submitted Date  ICMJE February 5, 2015
Results First Posted Date  ICMJE March 3, 2015
Last Update Posted Date March 3, 2015
Study Start Date  ICMJE July 2009
Actual Primary Completion Date June 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 2, 2015)
  • 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 ]
    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 ]
    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
Original Primary Outcome Measures  ICMJE
 (submitted: June 25, 2009)
Progression-free survival [ Time Frame: assessed every 9 weeks (after every 3rd cycle) until progression ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 2, 2015)
  • 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 ]
    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 ]
    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 ]
  • 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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 25, 2009)
  • Overall response; clinical benefit rate; time to tumor progression; overall survival [ Time Frame: from assessments every 9 weeks (after every 3rd cycle); overall survival monitored for at least 24 months ]
  • Adverse events; laboratory parameters [ Time Frame: every 3 weeks at treatment visit throughout study ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Avastin (Bevacizumab) + Xeloda (Capecitabine)as Maintenance Therapy in Patients With HER2-Negative Metastatic Breast Cancer
Official Title  ICMJE 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
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE
  • 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)
Study Arms  ICMJE
  • Active Comparator: Avastin (bevacizumab)
    Intervention: Drug: bevacizumab [Avastin]
  • Experimental: Avastin (bevacizumab) + Xeloda (capecitabine)
    Interventions:
    • Drug: bevacizumab [Avastin]
    • Drug: capecitabine [Xeloda]
Publications * Gligorov J, Doval D, Bines J, Alba E, Cortes P, Pierga JY, Gupta V, Costa R, Srock S, de Ducla S, Freudensprung U, Mustacchi G. Maintenance capecitabine and bevacizumab versus bevacizumab alone after initial first-line bevacizumab and docetaxel for patients with HER2-negative metastatic breast cancer (IMELDA): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014 Nov;15(12):1351-60. doi: 10.1016/S1470-2045(14)70444-9. Epub 2014 Sep 28.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 2, 2015)
287
Original Estimated Enrollment  ICMJE
 (submitted: June 25, 2009)
360
Actual Study Completion Date  ICMJE June 2014
Actual Primary Completion Date June 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Brazil,   China,   Egypt,   France,   Hong Kong,   India,   Italy,   Poland,   Saudi Arabia,   Spain,   Turkey
Removed Location Countries Morocco,   Portugal
 
Administrative Information
NCT Number  ICMJE NCT00929240
Other Study ID Numbers  ICMJE MO22223
2008-006872-31
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date March 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP