A PHASE III, MULTICENTER, RANDOMIZED,PLACEBO-CONTROLLED TRIAL EVALUATINGTHE EFFICACY AND SAFETY OF BEVACIZUMABIN COMBINATION WITH CHEMOTHERAPYREGIMENS IN SUBJECTS WITH PREVIOUSLYTREATED METASTATIC BREAST CANCER - Ribbon-2

Phase 1

• Conditions: Previously Treated Metastatic Breast Cancer; MedDRA version: 8.1Level: LLTClassification code 10027475Term: Metastatic breast cancer

• Registration Number: EUCTR2006-006507-36-CZ
• Lead Sponsor: Genentech Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-06-04
• Last Update Posted: 5 December 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 697

Inclusion Criteria

Subjects must meet the following criteria to be eligible for study entry:
• Signed Informed Consent Form
• = 18 years of age
• Histologically confirmed carcinoma of the breast with measurable or
non-measurable metastatic disease that has progressed
Subjects with a history of brain metastasis are eligible for study participation,
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, as ascertained by clinical examination and
brain imaging (MRI or CT scans) during the screening period. CT scan with
contrast or MRI scan of the brain must be performed at least 3 weeks after
completion of all therapy to the brain.
Treatment for brain metastasis may include the following: WBRT, SRS
(Gamma knife, LINAC, or equivalent), or a combination as deemed
appropriate by the treating physician. Radiotherapy and stereotactic
radiosurgery must be completed at least 4 weeks prior to Day 0.
Subjects may also have neurosurgical resection. Neurosurgery must be
completed at least 6 weeks prior to Day 0, and brain biopsy must be
completed at least 4 weeks prior to Day 0.
• Progression of disease during or following administration of one
(non-investigational) chemotherapy regimen, defined as single-agent
chemotherapy administered prior to or during disease progression or a
pre-specified combination or sequence of cytotoxic agents administered in
the first-line setting
Subjects whose initial treatment changed prior to progression in the
first-line setting are ineligible unless the change occurred within 30 days
of initial treatment due to toxicity.
• 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Subjects who meet any of the following criteria will be excluded from study entry:
a. Disease Treatment History
• 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 MBC
• HER2-positive status
In general, HER2-positive status will be identified by a fluorescence in situ
hybridization (FISH) assay as evaluated at the institution or, if FISH is
unavailable, a 2 + or 3 + immunohistochemistry result (but the method of
identification may vary by region or institution). Patients who have unknown
HER2 status, and for whom determination of HER2 status is not possible,
are eligible for this study.
• Unknown ER and PR status
• Radiation therapy other than for palliation or brain metastasis, biologic therapy,
or chemotherapy for MBC within 21 days prior to Day 0
• Prior therapy with bevacizumab or other VEGF pathway–targeted therapy
b. Bevacizumab Exclusion Criteria
• Untreated brain metastasis
• Inadequately controlled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg on anti-hypertensive medications
• Unstable angina
• New York Heart Association Grade II or greater CHF (see Appendix C)
• 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
Subjects with fractures secondary to metastatic disease are eligible after
appropriate radiotherapy.
• History of anaphylactic reaction to monoclonal antibody therapy not controlled with
treatment premedication
c. General Exclusion Criteria
• Inadequate organ function, as evidenced by any of the following laboratory
values:
Absolute neutrophil count < 1500/µL
Platelet count < 100,000/µL
Total bilirubin > 1.5 mg/dL
AST and/or ALT > 2 × the upper limit of normal (ULN) ( > 5 × the ULN in
subjects with known liver involvement)
Alkaline phosphatase >2 × the ULN (>5 × the ULN in subjects with known liver involvement and >7 x the ULN in subjects with known bone involvement)
Serum creatinine > 2.0 mg/dL
International normalized ratio (INR) > 1.5 × and/or activated partial
thromboplastin time > 1.5 × the ULN (except for subjects receiving
anti-coagulation therapy)
Urine protein to creatinine ratio > 1.0 at screening for U.S. subjects
(see Appendix F) or urine dipstick for proteinuria = 1+ at screening followed by
24-hour urine collection demonstrating > 1 g protein/24 hours for ROW subjects
• History of other malignancies within 5 years of Day 0, except for tumors wit

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified