Previously Treated Metastatic Breast Cancer MedDRA version: 8.1 Level: LLT Classification code 10027475 Term: Metastatic breast cancer
Conditions
Interventions
Trade Name: Avastin
Product Name: Bevacizumab
Pharmaceutical Form: Intravenous infusion
INN or Proposed INN: Bevacizumab
CAS Number: 216974-75-3
Current Sponsor code: RO487-6646
Concentration unit: mg
Sponsors
Genentech Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
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 Patients with a history of brain metastasis are eligible for study participation (U.S. 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, 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. Patients 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 (see Appendix B) • 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 proceduresfirst-line setting are ineligible unless the change occurred within 30 days of initial treatment due to toxicity. • ECOG performance status of 0 or 1 (see Appendix B) • 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
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 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 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 (>7 × 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 with a negligible risk for metastasis or death, such as adequ
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to determine the clinical benefit of the addition of bevacizumab to standard chemotherapy for previously treated MBC in subjects without brain metastasis as measured by PFS, assessed in a two-step, hierarchical manner, as follows: • Determination of the clinical benefit, as measured by PFS, of the addition of bevacizumab to non-capecitabine therapy, i.e., taxane (docetaxel, paclitaxel, paclitaxel protein-bound particles [Abraxane?]), gemcitabine, or vinorelbine therapy compared with these chemotherapies alone in subjects receiving second-line therapy for MBC • Determination of the clinical benefit, as measured by PFS, of the addition of bevacizumab to any protocol-allowed chemotherapy (taxane, capecitabine, gemcitabine, or vinorelbine) compared with chemotherapy alone in subjects receiving second-line therapy for MBC;Secondary Objective: The secondary objectives of this study are to evaluate the efficacy and safety of bevacizumab when combined with chemotherapy compared with chemotherapy alone in subjects without brain metastasis receiving second-line therapy for MBC, as measured by the following: • Estimation of the clinical benefit of the addition of bevacizumab to each chemotherapy regimen, with PFS estimates and confidence limits calculated within each chemotherapy stratum for bevacizumab and placebo • Determination of the clinical benefit, as measured by objective response rate, duration of objective response, one-year survival, and overall survival, of the addition of bevacizumab to standard chemotherapy options compared with standard chemotherapy alone • Comparison of the incidence of serious adverse events (SAEs), selected adverse events (see Section 3.3.3), and adverse events (AEs) leading to study treatment discontinuation ;Primary end point(s): Primary Endpoint: Progression-Free Survival Disease progression will be assessed by the investigator according to RECIST (see Appendix G). PFS is defined | — |
Countries
France, Italy, Latvia, Spain
Outcome results
None listed