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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00262067




Registration number
NCT00262067
Ethics application status
Date submitted
2/12/2005
Date registered
6/12/2005
Date last updated
13/12/2013

Titles & IDs
Public title
A Study Evaluating the Efficacy and Safety of Bevacizumab in Combination With Chemotherapy in Untreated Metastatic Breast Cancer (RIBBON 1)
Scientific title
A Multicenter, Phase III, Randomized, Placebo-controlled Trial Evaluating the Efficacy and Safety of Bevacizumab in Combination With Chemotherapy Regimens in Subjects With Previously Untreated Metastatic Breast Cancer
Secondary ID [1] 0 0
BO20094
Secondary ID [2] 0 0
AVF3694g
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Bevacizumab
Treatment: Drugs - Placebo
Treatment: Drugs - Chemotherapy

Experimental: Bevacizumab + chemotherapy - Patients received bevacizumab 15 mg/kg intravenously (IV) on Day 1 of every 21-day cycle plus one of several standard chemotherapies (taxanes, anthracycline-based regimens, or capecitabine) for metastatic breast cancer.

Placebo Comparator: Placebo + chemotherapy - Patients received placebo to bevacizumab administered IV on Day 1 of every 21-day cycle + 1 of several standard chemotherapies (taxanes, anthracycline-based regimens, or capecitabine) for metastatic breast cancer.


Treatment: Drugs: Bevacizumab
Patients received bevacizumab until disease progression, treatment limiting toxicity, or death due to any cause up to a maximum treatment duration of 48 months. The dose of bevacizumab was based on the patient's weight at either screening or baseline and remained the same throughout the blinded treatment phase of the study. The initial dose was delivered over 90±10 minutes. If there were no infusion related adverse events (fever and/or chills), the second infusion was delivered over 60±10 minutes. If the 60 minute infusion was well tolerated, all subsequent infusions were delivered over 30±10 minutes.

Treatment: Drugs: Placebo
Placebo consisted of the vehicle for bevacizumab without the antibody.

Treatment: Drugs: Chemotherapy
The chemotherapy was selected by the investigator prior to randomization. Chemotherapy treatment continued until disease progression, unacceptable toxicity, investigator/patient decision, or death, whichever occurred first, except for the anthracycline-based regimens, which had a maximum treatment duration of 8 cycles.
Taxanes - 1 of the following 2 taxanes on Day 1 of every 21-day cycle
Docetaxel 75-100 mg/m^2 IV
Paclitaxel protein-bound particles (Abraxane®) 260 mg/m^2 IV
Anthracyclines - 1 of the following 4 anthracycline-based regimens on Day 1 of every 21-day cycle
5-fluorouracil 500 mg/m^2 IV + epirubicin 90-100 mg/m^2 IV + cyclophosphamide 500 mg/m^2 IV
5-fluorouracil 500 mg/m^2 IV + doxorubicin 50 mg/m^2 IV + cyclophosphamide 500 mg/m^2 IV
Doxorubicin 50-60 mg/m^2 IV + cyclophosphamide 500-600 mg/m^2 IV
Epirubicin 90-100 mg/m^2 IV + cyclophosphamide 500-600 mg/m^2 IV
Capecitabine: 1000 mg/m^2 orally twice daily on Days 1-14 of each 21-day cycle
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free Survival (PFS) as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST)
Timepoint [1] 0 0
Baseline to the data cut-off date of 31 Jul 2008 (up to 2 years, 7 months)
Secondary outcome [1] 0 0
Objective Response as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST)
Timepoint [1] 0 0
Baseline to the data cut-off date of 31 Jul 2008 (up to 2 years, 7 months)
Secondary outcome [2] 0 0
Duration of Objective Response as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST)
Timepoint [2] 0 0
Baseline to the data cut-off date of 31 Jul 2008 (up to 2 years, 7 months)
Secondary outcome [3] 0 0
Overall Survival
Timepoint [3] 0 0
Baseline to the data cut-off of 23 Feb 2009 (up to 3 years, 2 months)
Secondary outcome [4] 0 0
1-year Survival
Timepoint [4] 0 0
Baseline to the data cut-off of 23 Feb 2009 (up to 3 years, 2 months)
Secondary outcome [5] 0 0
Progression-free Survival (PFS) as Determined by the Independent Review Committee Using Response Evaluation Criteria in Solid Tumors (RECIST)
Timepoint [5] 0 0
Baseline to the data cut-off date of 31 Jul 2008 (up to 2 years, 7 months)

Eligibility
Key inclusion criteria
- Histologically or cytologically confirmed adenocarcinoma of the breast, with
measurable or non-measurable locally recurrent or metastatic disease.

- Signed Informed Consent Form.

- Age = 18 years.

- For women of childbearing potential, use of accepted and effective method of
non-hormonal contraception.

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

- Ability and capacity to comply with study and follow-up procedures.

- For anthracycline cohort only: Adequate left ventricular function at study entry,
defined as a left ventricular ejection fraction (LVEF) = 50% by either multigated
acquisition (MUGA) scan scan or echocardiography (ECHO).

- For subjects who have received recent radiation therapy, recovery prior to baseline
(Day 0) from any significant (Grade = 3) acute toxicity.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Unknown human epidermal growth factor receptor 2 (HER2) status or known HER2-positive
status.

- Prior chemotherapy for locally recurrent or metastatic disease.

- Prior hormonal therapy less than 1 week prior to Day 0.

- Prior adjuvant or neoadjuvant chemotherapy within 12 months prior to Day 0.

- For anthracycline cohort only: Prior anthracycline as part of neoadjuvant or adjuvant
therapy for localized breast cancer.

- Investigational therapy within 28 days of Day 0.

- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to Day 0, or anticipation of need for major surgical procedure during the course
of the study.

- Minor surgical procedures, such as fine needle aspirations or core biopsies, within 7
days prior to Day 0.

- Prior therapy with bevacizumab, sorafenib, sunitinib, or other vascular endothelial
growth factor (VEGF) pathway-targeted therapy.

- Known brain or other central nervous system (CNS) metastases.

- Blood pressure of > 150/100 mmHg.

- Unstable angina.

- New York Heart Association (NYHA) Grade II or greater congestive heart failure (CHF).

- History of myocardial infarction within 6 months prior to Day 0.

- 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.

- 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.

- Pregnancy (positive serum pregnancy test) or lactation.

- Inadequate organ function, as evidenced by any of the following laboratory values:
Absolute neutrophil count < 1500/uL; platelet count < 100,000/uL; total bilirubin >
1.5 mg/dL; alkaline phosphatase, AST, and/or ALT > 2x upper limit of normal (ULN) (>
5x ULN in subjects with known liver or, for alkaline phosphatase elevations, bone
involvement); alkaline phosphatase > 2x ULN (> 7x ULN in subjects with known bone
involvement); serum creatinine > 2.0 mg/dL; partial thromboplastin time (PTT) and/or
either international normalized ratio (INR) or prothrombin time (PT) > 1.5x upper
limit of normal (except for subjects receiving anti-coagulation therapy); urine
protein/creatinine ratio > 1.0 at screening for U.S. subjects, or urine dipstick for
proteinuria >/= 1+ at screening followed by 24-hour urine collection demonstrating > 1
g protein/24 hr for ex-U.S. subjects.

- Uncontrolled serious medical or psychiatric illness.

- Active infection requiring intravenous (iv) antibiotics at Day 0.

- 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
(subjects with a history of bilateral breast cancer will be eligible).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Unknown status
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/12/2005
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2013
Actual
Sample size
Target
Accrual to date
Final
1237
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
- Geelong
Recruitment hospital [2] 0 0
- Malvern
Recruitment hospital [3] 0 0
- Melbourne
Recruitment hospital [4] 0 0
- Perth
Recruitment hospital [5] 0 0
- Southport
Recruitment hospital [6] 0 0
- Wahroonga
Recruitment hospital [7] 0 0
- Waratah
Recruitment hospital [8] 0 0
- Wollongong
Recruitment postcode(s) [1] 0 0
3220 - Geelong
Recruitment postcode(s) [2] 0 0
3144 - Malvern
Recruitment postcode(s) [3] 0 0
3002 - Melbourne
Recruitment postcode(s) [4] 0 0
6008 - Perth
Recruitment postcode(s) [5] 0 0
4215 - Southport
Recruitment postcode(s) [6] 0 0
2076 - Wahroonga
Recruitment postcode(s) [7] 0 0
2298 - Waratah
Recruitment postcode(s) [8] 0 0
2500 - Wollongong
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Iowa
Country [3] 0 0
United States of America
State/province [3] 0 0
Kansas
Country [4] 0 0
Brazil
State/province [4] 0 0
Porto Alegre
Country [5] 0 0
Brazil
State/province [5] 0 0
Rio de Janeiro
Country [6] 0 0
Brazil
State/province [6] 0 0
Salvador
Country [7] 0 0
Brazil
State/province [7] 0 0
Santo Andre
Country [8] 0 0
Brazil
State/province [8] 0 0
Sao Paulo
Country [9] 0 0
Canada
State/province [9] 0 0
Manitoba
Country [10] 0 0
Canada
State/province [10] 0 0
Quebec
Country [11] 0 0
France
State/province [11] 0 0
Marseille
Country [12] 0 0
France
State/province [12] 0 0
Paris
Country [13] 0 0
France
State/province [13] 0 0
Reims
Country [14] 0 0
France
State/province [14] 0 0
Saint Herblain
Country [15] 0 0
France
State/province [15] 0 0
Strasbourg
Country [16] 0 0
Greece
State/province [16] 0 0
Athens
Country [17] 0 0
Greece
State/province [17] 0 0
Hania
Country [18] 0 0
Greece
State/province [18] 0 0
Heraklion
Country [19] 0 0
Greece
State/province [19] 0 0
Patras
Country [20] 0 0
Greece
State/province [20] 0 0
Thessaloniki
Country [21] 0 0
Guatemala
State/province [21] 0 0
Guatemala City
Country [22] 0 0
Korea, Republic of
State/province [22] 0 0
Kyunggi-do
Country [23] 0 0
Korea, Republic of
State/province [23] 0 0
Seoul
Country [24] 0 0
Mexico
State/province [24] 0 0
Acapulco
Country [25] 0 0
Mexico
State/province [25] 0 0
Aguascalientes
Country [26] 0 0
Mexico
State/province [26] 0 0
Merida
Country [27] 0 0
Mexico
State/province [27] 0 0
Monterrey
Country [28] 0 0
Netherlands
State/province [28] 0 0
Amstelveen
Country [29] 0 0
Netherlands
State/province [29] 0 0
Apeldoorn
Country [30] 0 0
Netherlands
State/province [30] 0 0
Delft
Country [31] 0 0
Norway
State/province [31] 0 0
Oslo
Country [32] 0 0
Panama
State/province [32] 0 0
Panama City
Country [33] 0 0
Peru
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Callao
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Philippines
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Quezon City
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Russian Federation
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Chelyabinsk
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Russian Federation
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Ivanovo
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Russian Federation
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Kazan
Country [38] 0 0
Russian Federation
State/province [38] 0 0
Moscow
Country [39] 0 0
Russian Federation
State/province [39] 0 0
Novosibirsk
Country [40] 0 0
Russian Federation
State/province [40] 0 0
Obninsk
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Russian Federation
State/province [41] 0 0
Ryazan
Country [42] 0 0
Russian Federation
State/province [42] 0 0
Samara
Country [43] 0 0
Russian Federation
State/province [43] 0 0
St Petersburg
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Russian Federation
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UFA
Country [45] 0 0
Singapore
State/province [45] 0 0
Singapore
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Spain
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Córdoba
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Spain
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Elche
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Spain
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Girona
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Spain
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La Coruna
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Spain
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La Laguna
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Spain
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Madrid
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Spain
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Santander
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Spain
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Sevilla
Country [54] 0 0
Spain
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Valencia
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Spain
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Zaragoza
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Sweden
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Gaevle
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Sweden
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Uppsala
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Sweden
State/province [58] 0 0
Örebro
Country [59] 0 0
Taiwan
State/province [59] 0 0
Tainan
Country [60] 0 0
Taiwan
State/province [60] 0 0
Taoyuan
Country [61] 0 0
Ukraine
State/province [61] 0 0
Cherkassy
Country [62] 0 0
Ukraine
State/province [62] 0 0
Dnipropetrovsk
Country [63] 0 0
Ukraine
State/province [63] 0 0
Kiev
Country [64] 0 0
Ukraine
State/province [64] 0 0
Lvov
Country [65] 0 0
Ukraine
State/province [65] 0 0
Odessa
Country [66] 0 0
Ukraine
State/province [66] 0 0
Zaporozhye
Country [67] 0 0
United Kingdom
State/province [67] 0 0
Chelsmford
Country [68] 0 0
United Kingdom
State/province [68] 0 0
Cottingham
Country [69] 0 0
United Kingdom
State/province [69] 0 0
Epping
Country [70] 0 0
United Kingdom
State/province [70] 0 0
Huddersfield
Country [71] 0 0
United Kingdom
State/province [71] 0 0
Nottingham
Country [72] 0 0
United Kingdom
State/province [72] 0 0
Sheffield
Country [73] 0 0
United Kingdom
State/province [73] 0 0
Swansea
Country [74] 0 0
Uruguay
State/province [74] 0 0
Montevideo

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Genentech, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a Phase III, multicenter, randomized, placebo-controlled trial designed to evaluate
the efficacy and safety of bevacizumab in combination with chemotherapy compared with
chemotherapy alone in subjects with previously untreated metastatic breast cancer.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00262067
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Leonardo Faoro, MD
Address 0 0
Genentech, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00262067