Metastatic Breast CancerPhase 3NCT00281697
A Study to Evaluate the Safety and Efficacy of Bevacizumab in Combination With Chemotherapy in Previously Treated Metastatic Breast Cancer (RIBBON 2)
A Phase 3 study testing Bevacizumab and Standard chemotherapy in people with Metastatic Breast Cancer, run by Genentech, Inc..
Trial summary
This phase III, multicenter, randomized, placebo-controlled, blinded trial is designed to evaluate the efficacy and safety of bevacizumab when combined with standard chemotherapy compared with chemotherapy alone in subjects with previously treated metastatic breast cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Breast Cancer
- What is being tested?
- Bevacizumab and Standard chemotherapy
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 684 participants
- Where
- No sites listed yet
- Study dates
- Feb 2006to Sep 2012
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed informed consent form.
- ≥ 18 years of age.
- Histologically confirmed carcinoma of the breast with measurable or non-measurable metastatic disease that has progressed (patients with a history of brain metastasis are eligible for study participation [USA only], as long as their brain metastases have been treated and they have no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone).
- Progression of disease during or following administration of one (non-investigational) chemotherapy regimen administered in the first-line setting.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- For women of childbearing potential, use of an effective means of non-hormonal contraception.
- Life expectancy ≥ 3 months.
- Willingness and capacity to comply with study and follow-up procedures.
Who cannot join
- Prior hormonal therapy only as treatment for metastatic disease without chemotherapy. Patients must have received chemotherapy for their metastatic disease in the first-line setting. Hormone therapy alone is not allowed.
- For subjects who have received prior anthracycline-based therapy, documentation of left ventricular ejection fraction < 50% by either multiple gated acquisition (MUGA) or echocardiogram (ECHO).
- Treatment with more than one prior cytotoxic regimen for metastatic breast cancer (MBC).
- HER2-positive status (patients who have unknown HER2 status, and for whom determination of HER2 status is not possible, are eligible for this study).
- Unknown estrogen receptor (ER) and progesterone receptor (PR) status.
- Radiation therapy other than for palliation or brain metastasis, biologic therapy, or chemotherapy for MBC within 21 days prior to Day 0 (Day 1 of Cycle 1 of treatment).
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- Prior therapy with bevacizumab or other vascular endothelial growth factor (VEGF) pathway-targeted therapy.
- Untreated brain metastasis.
- Inadequately controlled hypertension.
- Unstable angina.
- New York Heart Association Grade II or greater congestive heart failure (CHF).
- History of myocardial infarction within 6 months prior to Day 0 (the day of the first bevacizumab/placebo infusion).
- History of stroke or transient ischemic attack within 6 months prior to Day 0.
- Clinically significant peripheral vascular disease.
- Evidence of bleeding diathesis or coagulopathy.
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0; anticipation of need for major elective surgical procedure during the study.
- Minor surgical procedures, fine-needle aspirations, or core biopsies within 7 days prior to Day 0.
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 0.
- Serious, non-healing wound, ulcer, or bone fracture.
- History of anaphylactic reaction to monoclonal antibody therapy not controlled with treatment premedication.
- History of other malignancies within 5 years of Day 0, except for tumors with a negligible risk for metastasis or death, such as adequately controlled basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
- inadequate organ function.
- Pregnancy (positive serum pregnancy test) or lactation.
- Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the subject at high risk from treatment complications.
About this study
Official title: A Phase III, Multicenter, Randomized, Placebo-controlled Trial Evaluating the Efficacy and Safety of Bevacizumab in Combination With Chemotherapy Regimens in Subjects With Previously Treated Metastatic Breast Cancer
This phase III, multicenter, randomized, placebo-controlled, blinded trial is designed to evaluate the efficacy and safety of bevacizumab when combined with standard chemotherapy compared with chemotherapy alone in subjects with previously treated metastatic breast cancer.
Read the detailed description
For all Outcome Measures except Overall Survival and One-year Survival, the Time Frame was from Baseline to data cut-off for analysis of the primary Outcome Measure (up to 3 years 2 months). For the Outcome Measures Overall Survival and One-year Survival, the Time Frame was from Baseline to the end of the study (up to 6 years, 7 months).
- Conditions
- Metastatic Breast Cancer
- Being tested
- Bevacizumab, Placebo, Standard chemotherapy
- Keywords
- Ribbon 2, Avastin, MBC, Breast cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BevacizumabDrug
Also called Avastin
The dose of bevacizumab was based on a patient's weight at baseline and remained the same throughout the study.
PlaceboDrug
Standard chemotherapyDrug
Patients received one of the following four standard chemotherapies for metastatic breast cancer.
- Taxane - Paclitaxel (Taxol) 90 mg/m^2 IV every week for 3 weeks followed by 1 week of rest; paclitaxel (Taxol) 175 mg/m^2 IV every 3 weeks, or paclitaxel protein-bound particles (Abraxane) 260 mg/m^2 IV every 3 weeks; or docetaxel (Taxotere) 75-100 mg/m^2 IV every 3 weeks.
- Gemcitabine (Gemzar) 1250 mg/m^2 IV on Days 1 and 8 of each 3-week cycle.
- Vinorelbine (Navelbine) 30 mg/m^2 IV every week of each 3-week cycle.
- Capecitabine (Xeloda) 1000 mg/m^2 orally twice daily on Days 1-14 of each 3-week cycle.
| Study group | Role | What they receive |
|---|---|---|
| Standard chemotherapy + bevacizumab | Experimental | Patients received one of several standard chemotherapies for metastatic breast cancer plus bevacizumab in a dose of either 10 mg/kg intravenously (IV) every 2 weeks or 15 mg/kg IV every 3 weeks depending upon the schedule of chemotherapy chosen. Receives: Drug: Bevacizumab; Drug: Standard chemotherapy |
| Standard chemotherapy + placebo | Placebo comparator | Patients received one of several standard chemotherapies for metastatic breast cancer plus placebo to bevacizumab administered IV either every 2 weeks or every 3 weeks depending upon the schedule of chemotherapy chosen. Receives: Drug: Placebo; Drug: Standard chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival
PFS was defined as the time from randomization to first documented disease progression (PD) as determined by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) or death due to any cause, whichever occurred first. For target lesions, PD was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter recorded since treatment started or the appearance of 1 or more new lesions. For non-target lesions, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. Target lesions should be selected on the basis of their size (those with the longest diameter) and their suitability for accurate repeated measurements by imaging techniques or clinically. All measurable lesions up to a maximum of 5 lesions per organ and 10 lesions in total, representative of all involved organs, should be identified as target lesions.
Measured: Baseline to data cut-off for analysis of the primary Outcome Measure (up to 3 years, 2 months)
Secondary outcomes (5)
Progression-free Survival Within Individual Standard Chemotherapy Cohorts (Taxanes, Gemcitabine, Capecitabine, and Vinorelbine)
Progression-free survival was defined as the time from randomization to first documented disease progression as determined by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) or death due to any cause, whichever occurred first. Results are reported for each of the 4 standard chemotherapy cohorts used in the study.
Measured: Baseline to data cut-off for analysis of the primary Outcome Measure (up to 3 years, 2 months)
Overall Survival
Overall survival was defined as the time from randomization to death from any cause.
Measured: Baseline to the end of the study (up to 6 years, 7 months)
One-year Survival
Percentage of patients who survived 1 year in the study.
Measured: Baseline to the end of the study (up to 6 years, 7 months)
Objective Response
A patient had an objective response if they had a complete response or a partial response determined on two consecutive occasions ≥ 4 weeks apart as determined by the investigator using RECIST. For target lesions, a complete response was defined as the disappearance of all target lesions; a partial response was defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. For non-target lesions, a complete response was defined as the disappearance of all non-target lesions; a partial response was defined as the persistence of 1 or more non-target lesions.
Measured: Baseline to data cut-off for analysis of the primary Outcome Measure (up to 3 years, 2 months)
Duration of Objective Response
Duration of objective response was defined as the time from the initial response to documented disease progression or death from any cause, whichever occurred first. Duration of objective response was only analyzed in patients who achieved an objective response.
Measured: Baseline to data cut-off for analysis of the primary Outcome Measure (up to 3 years, 2 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2006 (estimated)
- Study startFeb 2006
- Primary completionMar 2009
- Study completionSep 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Metastatic Breast CancerStudies of the same condition, open and under way.
- More trials run by Genentech, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 684 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genentech, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Leo Faoro, MD, Study director, Genentech, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00281697
- Sponsor's protocol ID
- AVF3693g
- Status last verified
- Jul 2013
- First submitted
- 23 Jan 2006
- Last updated
- 26 Jul 2013
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 26 Jul 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III, Multicenter, Randomized, Placebo-controlled Trial Evaluating the Efficacy and Safety of Bevacizumab in Combination With Chemotherapy Regimens in Subjects With Previously Treated Metastatic Breast Cancer
- ClinicalTrials.gov ID
- NCT00281697
- Acronym / sponsor ID
- AVF3693g
- Conditions
- Metastatic Breast Cancer
- Keywords
- Ribbon 2, Avastin, MBC, Breast cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 684 participants (actual)
- Lead sponsor
- Genentech, Inc.Industry (pharma, biotech, devices)
- Study start
- Feb 2006
- Primary completion
- Mar 2009 (actual)
- Study completion
- Sep 2012 (actual)
- First posted
- 25 Jan 2006 (estimated)
- Results
- Posted 24 Sep 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase III, multicenter, randomized, placebo-controlled, blinded trial is designed to evaluate the efficacy and safety of bevacizumab when combined with standard chemotherapy compared with chemotherapy alone in subjects with previously treated metastatic breast cancer.
Detailed description
For all Outcome Measures except Overall Survival and One-year Survival, the Time Frame was from Baseline to data cut-off for analysis of the primary Outcome Measure (up to 3 years 2 months). For the Outcome Measures Overall Survival and One-year Survival, the Time Frame was from Baseline to the end of the study (up to 6 years, 7 months).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard chemotherapy + bevacizumab | Experimental | Drug: Bevacizumab, Drug: Standard chemotherapyPatients received one of several standard chemotherapies for metastatic breast cancer plus bevacizumab in a dose of either 10 mg/kg intravenously (IV) every 2 weeks or 15 mg/kg IV every 3 weeks depending upon the schedule of chemotherapy chosen. |
| Standard chemotherapy + placebo | Placebo comparator | Drug: Placebo, Drug: Standard chemotherapyPatients received one of several standard chemotherapies for metastatic breast cancer plus placebo to bevacizumab administered IV either every 2 weeks or every 3 weeks depending upon the schedule of chemotherapy chosen. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Signed informed consent form.
- ≥ 18 years of age.
- Histologically confirmed carcinoma of the breast with measurable or non-measurable metastatic disease that has progressed (patients with a history of brain metastasis are eligible for study participation [USA only], as long as their brain metastases have been treated and they have no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone).
- Progression of disease during or following administration of one (non-investigational) chemotherapy regimen administered in the first-line setting.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Key exclusion criteria (24 listed)
- Prior hormonal therapy only as treatment for metastatic disease without chemotherapy. Patients must have received chemotherapy for their metastatic disease in the first-line setting. Hormone therapy alone is not allowed.
- For subjects who have received prior anthracycline-based therapy, documentation of left ventricular ejection fraction < 50% by either multiple gated acquisition (MUGA) or echocardiogram (ECHO).
- Treatment with more than one prior cytotoxic regimen for metastatic breast cancer (MBC).
- HER2-positive status (patients who have unknown HER2 status, and for whom determination of HER2 status is not possible, are eligible for this study).
- Unknown estrogen receptor (ER) and progesterone receptor (PR) status.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BevacizumabAlso: AvastinThe dose of bevacizumab was based on a patient's weight at baseline and remained the same throughout the study. | Drug | Standard chemotherapy + bevacizumab |
| Placebo | Drug | Standard chemotherapy + placebo |
| Standard chemotherapyPatients received one of the following four standard chemotherapies for metastatic breast cancer. 1. Taxane - Paclitaxel (Taxol) 90 mg/m^2 IV every week for 3 weeks followed by 1 week of rest; paclitaxel (Taxol) 175 mg/m^2 IV every 3 weeks, or paclitaxel protein-bound particles (Abraxane) 260 mg/m^2 IV every 3 weeks; or docetaxel (Taxotere) 75-100 mg/m^2 IV every 3 weeks. 2. Gemcitabine (Gemzar) 1250 mg/m^2 IV on Days 1 and 8 of each 3-week cycle. 3. Vinorelbine (Navelbine) 30 mg/m^2 IV every week of each 3-week cycle. 4. Capecitabine (Xeloda) 1000 mg/m^2 orally twice daily on Days 1-14 of each 3-week cycle. | Drug | Standard chemotherapy + bevacizumab, Standard chemotherapy + placebo |
Primary outcome
Progression-free Survival
Time frame: Baseline to data cut-off for analysis of the primary Outcome Measure (up to 3 years, 2 months)
PFS was defined as the time from randomization to first documented disease progression (PD) as determined by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) or death due to any cause, whichever occurred first. For target lesions, PD was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter recorded since treatment started or the appearance of 1 or more new lesions. For non-target lesions, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. Target lesions should be selected on the basis of their size (those with the longest diameter) and their suitability for accurate repeated measurements by imaging techniques or clinically. All measurable lesions up to a maximum of 5 lesions per organ and 10 lesions in total, representative of all involved organs, should be identified as target lesions.
5 secondary outcomes
Progression-free Survival Within Individual Standard Chemotherapy Cohorts (Taxanes, Gemcitabine, Capecitabine, and Vinorelbine)
Time frame: Baseline to data cut-off for analysis of the primary Outcome Measure (up to 3 years, 2 months)
Overall Survival
Time frame: Baseline to the end of the study (up to 6 years, 7 months)
One-year Survival
Time frame: Baseline to the end of the study (up to 6 years, 7 months)
Objective Response
Time frame: Baseline to data cut-off for analysis of the primary Outcome Measure (up to 3 years, 2 months)
Duration of Objective Response
Time frame: Baseline to data cut-off for analysis of the primary Outcome Measure (up to 3 years, 2 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jul 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Leo Faoro, MD study director
Genentech, Inc.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Bevacizumab and Standard chemotherapy in people with Metastatic Breast Cancer, run by Genentech, Inc..
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Jul 2013. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Sep 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free Survival (time frame: Baseline to data cut-off for analysis of the primary Outcome Measure (up to 3 years, 2 months)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jul 2013.