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

March 2, 2015 updated by: Hoffmann-La Roche

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

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 Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
287

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
    • CE
      • Fortaleza, CE, Brazil, 60336-550
    • MG
      • Belo Horizonte, MG, Brazil, 30190-130
    • RJ
      • Rio de Janeiro, RJ, Brazil, 20560-120
    • RS
      • Ijui, RS, Brazil, 98700-000
      • Porto Alegre, RS, Brazil, 90035-003
    • SP
      • Jau, SP, Brazil, 17210-080
      • Santo Andre, SP, Brazil, 09060-650
      • Sao Paulo, SP, Brazil, 01246-000
      • Sao Paulo, SP, Brazil, 08270-070
  • China
      • Beijing, China, 100021
      • Beijing, China, 100071
      • Beijing, China, 100853
      • Hangzhou, China, 310022
      • Hangzhou, China, 310009
      • Shanghai, China, 200032
  • Egypt
      • Alexandria, Egypt, 11737
      • Cairo, Egypt, 11796
  • France
      • Amiens, France, 80090
      • Angers, France, 49933
      • Besancon, France, 25030
      • Bobigny, France, 93009
      • Dijon, France, 21079
      • Hyeres, France, 83400
      • Le Coudray, France, 28630
      • Lille, France, 59000
      • Paris, France, 75970
      • Paris, France, 75231
      • Perigueux, France, 24000
      • Rodez, France, 12027
      • St Priest En Jarez, France, 42271
      • Strasbourg, France, 67010
  • Hong Kong
      • Hong Kong, Hong Kong
      • Hong Kong, Hong Kong, 852
  • India
      • Bangalore, India, 560027
      • Hyderabad, India, 500034
      • Mumbai, India, 400012
      • Mumbai, India, 400020
      • New Delhi, India, 110 060
      • New Delhi, India, 110085
  • Italy
    • Campania
      • Napoli, Campania, Italy, 80131
    • Friuli-Venezia Giulia
      • Trieste, Friuli-Venezia Giulia, Italy, 34100
    • Liguria
      • Genova, Liguria, Italy, 16132
    • Lombardia
      • Saronno, Lombardia, Italy, 21047
    • Puglia
      • Brindisi, Puglia, Italy, 72100
    • Toscana
      • Antella (FI), Toscana, Italy, 50011
  • Poland
      • Bydgoszcz, Poland, 85-796
      • Wroclaw, Poland, 53-413
  • Saudi Arabia
      • Dammam, Saudi Arabia, 31444
      • Jeddah, Saudi Arabia, 21497
      • Jeddah, Saudi Arabia, 21589
  • Spain
      • Jaen, Spain, 23007
      • Malaga, Spain, 29010
      • Toledo, Spain, 45004
      • Valencia, Spain, 46026
    • Alicante
      • Alcoy, Alicante, Spain, 03804
    • Barcelona
      • Sabadell, Barcelona, Barcelona, Spain, 08208
    • Ciudad Real
      • Alcazar de S. Juan, Ciudad Real, Spain, 13600
    • Vizcaya
      • Barakaldo, Vizcaya, Spain, 48903
  • Turkey
      • Ankara, Turkey, 06500
      • Ankara, Turkey, 06800
      • Antalya, Turkey, 07070
      • Istanbul, Turkey, 34000
      • Sıhhiye, ANKARA, Turkey, 06100

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
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)
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
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

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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).
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)
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.
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
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.
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)
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.
Years 1 and 2
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.
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 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.
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)
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.
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)
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.
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)
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.
Screening and at the end of every third cycle until randomization for an average of 18 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hoffmann-La Roche

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2009

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2014

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 16, 2009

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 25, 2009

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 26, 2009

Study Record Updates

Last Update Posted (ESTIMATE)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 3, 2015

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 2, 2015

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MO22223
  • 2008-006872-31

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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