HER2-negative metastatic breast cancer. MedDRA version: 18.1 Level: LLT Classification code 10027475 Term: Metastatic breast cancer System Organ Class: 100000004864
Conditions
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically or cytologically confirmed, HER2 negative adenocarcinoma of the breast, with measurable or non-measurable locally recurrent or metastatic disease. Locally recurrent disease must not be amenable to resection with curative intent. 2. Signed Informed Consent Form 3. Age = 18 years 4. ECOG performance status of 0 or 1 5. Ability and capacity to comply with study and follow up procedures 6. For men and women with reproductive potential (women =65 years) yes F.1.3.1 Number of subjects for this age range 96
Exclusion criteria
Exclusion criteria: Disease-Specific Exclusions 1. HER2-positive status. 2. Prior chemotherapy for locally recurrent or metastatic disease 3. Prior hormonal therapy 150 mmHg and/or diastolic blood pressure > 100 mmHg) 15. Prior history of hypertensive crisis or hypertensive encephalopathy 16. New York Heart Association Class II or greater, CHF/left ventricular ejection fraction < 55% 17. History of myocardial infarction or unstable angina within 6 months prior to randomization 18. History of stroke or transient ischemic attack within 6 months prior to randomization 19. Known CNS disease except for treated brain metastasis. 20. Significant vascular disease 21. History of hemoptysis 22. Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation) 23. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to randomization or anticipation of need for major surgical procedure during the course of the study 24. Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to randomization 25. History of abdominal fistula or gastrointestinal (GI) perforation within 6 months prior to randomization 26. Serious, non-healing wound, active ulcer, or untreated bone fracture 27. Proteinuria at screening 28. Known hypersensitivity to any component of bevacizumab 29. Prior therapy with bevacizumab, sorafenib, sunitinib, or other VEGF pathway–targeted therapy Paclitaxel-Specific Exclusions 30. History of severe hypersensitivity to paclitaxel or to any of the excipients, especially macrogolglycerol ricinoleate 31. Paclitaxel should not be administered to patients with baseline neutrophil count <1500/mm3.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of bevacizumab + paclitaxel compared with placebo + paclitaxel as first-line treatment in patients with HER2-negative metastatic breast cancer as measured by: - PFS based on investigator tumor assessment in the intent-to treat (ITT) patient population - PFS based on investigator tumor assessment in ITT patients with high plasma VEGF-A levels;Secondary Objective: 1) To evaluate on the ITT population and the VEGF-A high subset the efficacy of bevacizumab + paclitaxel compared with placebo + paclitaxel as first-line treatment in patients with HER2-negative MBC as measured by: - OS - Objective response rate for patients with measurable disease at baseline, as assessed by investigator -Duration of objective response for patients with measurable disease at baseline - One-year survival 2) In addition, an interaction of treatment effect with the VEGF-A level for PFS will be performed in the ITT population 3) To evaluate the safety of bevacizumab + paclitaxel compared with placebo + paclitaxel as first-line treatment in patients with HER2-negative MBC, focusing on National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0) all-grade treatment-emergent adverse events.;Primary end point(s): Coprimary endpoints: 1) PFS in the intention-to-treat population (all randomized patients) 2) PFS in the patients with high VEGF-A levels;Timepoint(s) of evaluation of this end point: The primary analysis of PFS will occur when both (I) 326 PFS events in all patients and (II) 146 PFS events in the VEGF-A high subgroup have been observed. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Objective Response Rate 2) Duration of Objective Response 3) 1-year Survival Rate 4) Overall Survival 5) Treatment/VEGF-A Interaction Test for PFS;Timepoint(s) of evaluation of this end point: 1) Objective response, 2)duration of response, first IA of OS, AEs will be analyzed at the same time with final PFS. 3) Primary 1-year survival rate will be analyzed when OS crosses the boundary or at the time of final OS event maturity. 4) Final OS will also be conducted when both (I) approximately 309 deaths in all patients and (II) approximately 170 deaths in the VEGF-A high subgroup have been observed. 5)At the timepoint of the primary (final) analysis of PFS | — |
Countries
Argentina, Belgium, Brazil, Bulgaria, Chile, Germany, Italy, Japan, Korea, Republic of, Panama, Romania, Russian Federation, South Africa, Ukraine, United Kingdom, United States, Vietnam
Contacts
Public ContactTrial Information Support Line-TISL
F.Hoffmann-La Roche Ltd
Outcome results
None listed