A Study Evaluating the Efficacy and Safety of Bevacizumab in Combination With Chemotherapy in Untreated Metastatic Breast Cancer (RIBBON 1)

NCT00262067 | Unknown Phase 3 Results

• 2 other identifiers: AVF3694gBO20094
• Study Type: interventional
• Target: 1,237
• Locations: 22 countries
• Sites: 92

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.

Conditions

Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS) as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST)

  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.

  Baseline to the data cut-off date of 31 Jul 2008 (up to 2 years, 7 months)

Secondary Outcomes (5)

• Objective Response as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST)

  Baseline to the data cut-off date of 31 Jul 2008 (up to 2 years, 7 months)

• Duration of Objective Response as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST)

  Baseline to the data cut-off date of 31 Jul 2008 (up to 2 years, 7 months)

• Overall Survival

  Baseline to the data cut-off of 23 Feb 2009 (up to 3 years, 2 months)

• 1-year Survival

  Baseline to the data cut-off of 23 Feb 2009 (up to 3 years, 2 months)

• Progression-free Survival (PFS) as Determined by the Independent Review Committee Using Response Evaluation Criteria in Solid Tumors (RECIST)

  Baseline to the data cut-off date of 31 Jul 2008 (up to 2 years, 7 months)

Study Arms (2)

Bevacizumab + chemotherapy

EXPERIMENTAL

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.

Drug: Bevacizumab; Drug: Chemotherapy

Placebo + chemotherapy

PLACEBO COMPARATOR

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.

Drug: Placebo; Drug: Chemotherapy

Interventions

Bevacizumab DRUG

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.

Also known as: Avastin

Bevacizumab + chemotherapy

Placebo DRUG

Placebo consisted of the vehicle for bevacizumab without the antibody.

Placebo + chemotherapy

Chemotherapy DRUG

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 1. Docetaxel 75-100 mg/m\^2 IV 2. 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 1. 5-fluorouracil 500 mg/m\^2 IV + epirubicin 90-100 mg/m\^2 IV + cyclophosphamide 500 mg/m\^2 IV 2. 5-fluorouracil 500 mg/m\^2 IV + doxorubicin 50 mg/m\^2 IV + cyclophosphamide 500 mg/m\^2 IV 3. Doxorubicin 50-60 mg/m\^2 IV + cyclophosphamide 500-600 mg/m\^2 IV 4. 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

Bevacizumab + chemotherapy; Placebo + chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (92)

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Fullerton, California, 92835, United States

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Santa Barbara, California, 93105, United States

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Iowa City, Iowa, 52242, United States

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Sioux City, Iowa, 51101, United States

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Wichita, Kansas, 67214-3728, United States

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Geelong, 3220, Australia

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Malvern, 3144, Australia

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Melbourne, 3002, Australia

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Perth, 6008, Australia

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Southport, 4215, Australia

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Wahroonga, 2076, Australia

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Waratah, 2298, Australia

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Wollongong, 2500, Australia

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Porto Alegre, 91350-200, Brazil

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Rio de Janeiro, 22260-020, Brazil

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Salvador, 40170-110, Brazil

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Santo André, 09060-870, Brazil

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São Paulo, 03102-002, Brazil

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Winnipeg, Manitoba, R2H 2A6, Canada

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Montreal, Quebec, H2L 4M1, Canada

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Montreal, Quebec, H2W 1S6, Canada

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Marseille, 13273, France

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Paris, 75248, France

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Reims, 51100, France

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Saint-Herblain, 44805, France

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Strasbourg, 67010, France

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Athens, 11521, Greece

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Chania, 73300, Greece

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Heraklion, 71110, Greece

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Pátrai, 26500, Greece

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Thessaloniki, 57001, Greece

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Guatemala City, 01015, Guatemala

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Acapulco, 39670, Mexico

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Aguascalientes, 20230, Mexico

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Mérida, 97500, Mexico

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Monterrey, 64020, Mexico

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Monterrey, 64380, Mexico

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Amstelveen, 1186 AH, Netherlands

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Apeldoorn, 7334 DZ, Netherlands

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Delft, 2600 GA, Netherlands

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Oslo, 0310, Norway

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Oslo, 0407, Norway

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Panama City, Panama

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Callao, Peru

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Quezon City, 1114, Philippines

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Chelyabinsk, 454 087, Russia

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Ivanovo, 153040, Russia

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Kazan', 420029, Russia

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Kazan', 420111, Russia

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Moscow, 115478, Russia

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Moscow, 117837, Russia

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Moscow, 129128, Russia

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Novosibirsk, 630047, Russia

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Obninsk, 249036, Russia

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Ryazan, 390011, Russia

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Saint Petersburg, 197758, Russia

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Samara, 443066, Russia

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Ufa, 450054, Russia

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Singapore, 119228, Singapore

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Singapore, 169610, Singapore

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Kyunggi-do, 411-769, South Korea

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Seoul, 110-744, South Korea

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Seoul, 120-752, South Korea

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A Coruña, 15006, Spain

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Córdoba, 14004, Spain

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Elche, 03203, Spain

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Girona, 17007, Spain

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Madrid, 28034, Spain

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San Cristóbal de La Laguna, 38320, Spain

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Santander, 39008, Spain

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Seville, 41013, Spain

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Valencia, 46010, Spain

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Zaragoza, 50009, Spain

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Gävle, 80187, Sweden

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Örebro, 701 85, Sweden

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Uppsala, 751 85, Sweden

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Tainan, 704, Taiwan

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Taoyuan District, 333, Taiwan

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Cherkassy, 18009, Ukraine

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Dnipropetrovsk, 49102, Ukraine

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Kiev, 03115, Ukraine

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Lviv, 79031, Ukraine

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Odesa, 65055, Ukraine

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Zaporizhzhya, 69104, Ukraine

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Chelsmford, CM1 7ET, United Kingdom

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Cottingham, HU16 5JQ, United Kingdom

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Epping, CM16 6TN, United Kingdom

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Huddersfield, HD3 3EA, United Kingdom

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Nottingham, NG5 1PB, United Kingdom

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Sheffield, S1O 2SJ, United Kingdom

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Swansea, SA2 8QA, United Kingdom

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Montevideo, 11200, Uruguay

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Related Publications (1)

• Wedam SB, Beaver JA, Amiri-Kordestani L, Bloomquist E, Tang S, Goldberg KB, Sridhara R, Ibrahim A, Kim G, Kluetz P, McKee A, Pazdur R. US Food and Drug Administration Pooled Analysis to Assess the Impact of Bone-Only Metastatic Breast Cancer on Clinical Trial Outcomes and Radiographic Assessments. J Clin Oncol. 2018 Apr 20;36(12):1225-1231. doi: 10.1200/JCO.2017.74.6917. Epub 2018 Mar 9.

  PMID: 29522361 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Bevacizumab; Drug Therapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Therapeutics

Results Point of Contact

• Title: Medical Communications
• Organization: Genentech, Inc.

800 821-8590

Study Officials

• Leonardo Faoro, MD

  Genentech, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2005
• First Posted: December 6, 2005
• Study Start: December 1, 2005
• Primary Completion: July 1, 2008
• Study Completion: December 1, 2013
• Last Updated: December 13, 2013
• Results First Posted: October 25, 2013

Record last verified: 2013-11

Locations

GR (5); PE (1); NL (3); SG (2); GB (7); UR (1); ME (5); US (5); UA (6); PH (1); GU (1); TW (2); AU (8); KR (3); FR (5); PA (1); RU (13); ES (10); NO (2); CA (3); SE (3); BR (5)