Paclitaxel With or Without Bevacizumab in Treating Patients With Locally Recurrent or Metastatic Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies, such as bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or deliver cancer-killing substances to them. It is not yet known whether paclitaxel works better with or without bevacizumab in treating breast cancer. PURPOSE: This randomized phase III trial is to see if paclitaxel works better with or without bevacizumab in treating patients who have locally recurrent or metastatic breast cancer.

Detailed Description
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OBJECTIVES: Compare the time to treatment failure in patients with locally recurrent or metastatic breast cancer treated with paclitaxel with or without bevacizumab. Compare the objective response rate, duration of response, overall survival, and time to progression in patients treated with these regimens. Compare the toxicity of these regimens in these patients. Compare the quality of life of patients treated with these regimens. OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to disease-free interval (no more than 24 months vs more than 24 months), number of metastatic sites (less than 3 vs 3 or more), treatment with prior adjuvant chemotherapy (yes vs no), and estrogen receptor status (positive vs negative vs unknown). Patients are randomized to one of two treatment arms. Arm I: Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15 followed by bevacizumab IV over 30-90 minutes on days 1 and 15. Arm II: Patients receive paclitaxel as in arm I. In both arms, courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline and on day 1 of weeks 17 and 33. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 316-650 patients (158-325 per treatment arm) will be accrued for this study within 31 months.

Official Title
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A Randomized Phase III Tial Of Paclitaxel Versus Paclitaxel Plus Bevacizumab (rhuMAb VEGF) As First-Line Therapy For Locally Recurrent or Metastatic Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: bevacizumab
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed adenocarcinoma of the breast Locally recurrent disease that is not amenable to surgical resection with curative intent OR Metastatic disease No HER-2-overexpressing (3+) breast cancer unless previously treated with trastuzumab (Herceptin) Unknown HER-2 status allowed provided herceptin-based therapy inappropriate or not indicated No prior or radiologic evidence of CNS metastases, including previously treated, resected, or asymptomatic brain lesions or leptomeningeal involvement by head CT scan or MRI Hormone receptor status: Not specified PATIENT CHARACTERISTICS: Age: 18 and over Sex: Male or female Menopausal status: Not specified Performance status: ECOG 0-1 Life expectancy: Not specified Hematopoietic: Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 No prior bleeding diathesis Hepatic: Bilirubin no greater than 1.5 mg/dL SGOT no greater than 2 times upper limit of normal (ULN) (5 times ULN for known liver involvement) PT/PTT no greater than 1.5 times normal INR no greater than 1.5 times normal Renal: Creatinine no greater than 2.0 mg/dL No proteinuria by dipstick urinalysis Trace proteinuria allowed Proteinuria less than 500 mg by 24-hour urine collection if proteinuria at least 1+ by urinalysis Cardiovascular: No clinically significant cardiovascular disease No myocardial infarction within the past 12 months No unstable angina No prior deep vein thrombosis No grade 2 or greater peripheral vascular disease No uncontrolled congestive heart failure No uncontrolled hypertension (systolic blood pressure greater than 170 mmHg and diastolic blood pressure greater than 95 mm Hg) No prior cerebrovascular accident Pulmonary: No prior pulmonary embolism Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective non-hormonal contraception No history of seizures No non-healing wound or fracture No hypersensitivity to paclitaxel, Cremophor EL, Chinese hamster ovary cell products, or other recombinant human antibodies No active infection requiring parenteral antibiotics PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics Chemotherapy: No prior chemotherapy for locally recurrent or metastatic breast cancer At least 12 months since prior adjuvant or neoadjuvant taxane therapy At least 3 weeks since prior adjuvant chemotherapy Endocrine therapy: At least 3 weeks since prior hormonal therapy for locally recurrent or metastatic breast cancer Radiotherapy: At least 3 weeks since prior radiotherapy No prior radiotherapy to only site of disease No concurrent local radiotherapy for pain control or life-threatening situations (e.g, superior vena cava syndrome, spinal cord compression, or CNS metastases) Surgery: At least 4 weeks since prior major surgical procedure except placement of vascular access device or breast biopsy At least 7 days since prior minor surgical procedure, including placement of an access device or fine needle aspiration Other: At least 10 days since prior anticoagulant therapy (low-dose anticoagulant therapy to maintain patency of a vascular access device allowed) At least 10 days since prior and no concurrent daily aspirin (more than 325 mg/day) or other non-steroidal anti-inflammatory medication known to inhibit platelet function No concurrent dipyridamole, ticlopidine, clopidogrel, or cilostazol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Paclitaxel + Bevacizumab<br> | Drug: bevacizumab<br>* 10 mg/kg following paclitaxel treatment on weeks 1 and 3 of every 4-week cycle<br>* Other names: Avastin;Drug: Paclitaxel<br>* 90 mg/m2 IV infusion over 1 hour every week for 3 weeks followed by 1 week rest<br>|
| Active Comparator: Paclitaxel<br> | Drug: Paclitaxel<br>* 90 mg/m2 IV infusion over 1 hour every week for 3 weeks followed by 1 week rest<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival |  | Assessed every 3 months for 2 years, then every 6 months for 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IV breast cancer, recurrent breast cancer, male breast cancer