Docetaxel, Capecitabine, and Bevacizumab in Treating Patients With Metastatic Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as docetaxel and capecitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as bevacizumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Bevacizumab may also stop the growth of tumor cells by stopping blood flow to the tumor. Combining chemotherapy with monoclonal antibody therapy may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving docetaxel and capecitabine together with bevacizumab works in treating patients with metastatic breast cancer.

Detailed Description
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OBJECTIVES: Primary Determine the response rate in patients with metastatic breast cancer treated with docetaxel, capecitabine, and bevacizumab as first-line chemotherapy. Secondary Determine time to disease progression in patients treated with this regimen. Determine survival of patients treated with this regimen. Determine the toxicity profile of this regimen in these patients. Determine the duration of response in patients treated with this regimen. OUTLINE: This is a multicenter study. Patients receive docetaxel IV over 1 hour and bevacizumab IV over 30-90 minutes on day 1. Patients also receive oral capecitabine twice daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) receive at least 2 additional courses beyond CR. Patients are followed every 3 months for 1 year, every 6 months for 1 year, and then annually for 3 years.

Official Title
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Phase II Trial Of Docetaxel With Capecitabine And Bevacizumab As First-Line Chemotherapy For Patients With Metastatic Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Biological: bevacizumab
* Drug: capecitabine
* Drug: docetaxel


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed invasive breast cancer Clinical evidence of metastatic disease No bone metastases as the only evidence of metastasis Measurable disease At least 1 lesion ≥ 2.0 cm by CT scan or MRI OR ≥ 1.0 cm by spiral CT scan Lesions on chest x-ray allowed provided they are clearly defined and surrounded by aerated lung Clincal lesions only considered measurable when they are superficial (e.g., skin nodules or palpable lymph nodes) Target lesion must not have been exposed to prior radiotherapy unless disease has progressed since completion of radiotherapy The following are not considered measurable disease: Bone lesions Leptomeningeal disease Ascites Pleural or pericardial effusion Inflammatory breast disease Lymphangitis cutis or pulmonis Abdominal masses that are not confirmed and followed by imaging techniques Cystic lesions No HER2/neu-positive tumors by immunohistochemistry or amplified fluorescence in situ hybridization unless disease has progressed after trastuzumab (Herceptin®)-containing therapy alone or with antiestrogen hormonal therapy for metastatic disease OR trastuzumab is contraindicated Prior breast cancer allowed No prior or active brain metastases 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 At least 3 months Hematopoietic Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 8.0 g/dL No bleeding diathesis or uncontrolled coagulopathy Hepatic Bilirubin normal Meets 1 of the following criteria: AST and ALT normal AND alkaline phosphatase ≤ 5 times upper limit of normal (ULN) AST and ALT ≤ 1.5 times ULN AND alkaline phosphatase ≤ 2.5 times ULN AST and ALT ≤ 5 times ULN AND alkaline phosphatase normal Renal Creatinine clearance ≥ 30 mL/min No proteinuria OR Protein < 1 g by 24-hour urine collection No nephrotic syndrome Cardiovascular No uncontrolled hypertension (i.e., blood pressure > 160/90 mm Hg on ≥ 2 different observations ≥ 5 minutes apart) Blood pressure < 140/90 mm Hg on ≥ 3 different observations over ≥ 14 days, for patients who recently began or adjusted anti-hypertensive medication No atrial or venous thrombosis within the past month No clinically significant heart disease, including any of the following: Congestive heart failure Symptomatic coronary artery disease Uncontrolled cardiac arrhythmias Unstable angina No myocardial infarction within the past 12 months No history of cerebrovascular accident Pulmonary No hemoptysis within the past 6 months Gastrointestinal No lack of physical integrity of the upper gastrointestinal tract No malabsorption syndrome Able to receive oral medication Other No other stage III or IV invasive malignancy requiring treatment within the past 5 years No pre-existing peripheral neuropathy > grade 1 No history of allergy or hypersensitivity to study drugs, agents that are chemically similar to study drugs, or drugs that contain polysorbate 80 No prior severe reaction to fluoropyrimidines No known hypersensitivity to fluorouracil No known dihydropyrimidine dehydrogenase deficiency No active infection No significant medical condition that would preclude study participation Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 30 days after study participation PRIOR CONCURRENT THERAPY: Biologic therapy See Disease Characteristics No other concurrent biologic therapy Chemotherapy Prior adjuvant or neoadjuvant chemotherapy allowed for primary disease No prior chemotherapy for metastatic disease More than 4 weeks since prior cytotoxic chemotherapy More than 6 months since prior taxanes (e.g., docetaxel or paclitaxel) No other concurrent chemotherapy Endocrine therapy See Disease Characteristics Prior antiestrogen hormonal therapy allowed in the adjuvant or metastatic setting Radiotherapy See Disease Characteristics More than 4 weeks since prior radiotherapy to a target lesion Prior single-dose palliative radiotherapy allowed within the past 4 weeks No concurrent radiotherapy Surgery More than 4 weeks since prior major surgery Other More than 2 weeks since prior aspirin, anticoagulants, or thrombolytic agents Concurrent low-dose warfarin (1 mg/day) to maintain patency of vascular access device allowed More than 4 weeks since prior investigational agents No concurrent aspirin, anticoagulants, or thrombolytic agents No concurrent participation in another clinical trial involving investigational agents or procedures

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: docetaxel + bevacizumab + capecitabine<br>Patients receive docetaxel IV over 1 hour and bevacizumab IV over 30-90 minutes on day 1. Patients also receive oral capecitabine twice daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) receive at least 2 additional courses beyond CR. Patients are followed every 3 months for 1 year, every 6 months for 1 year, and then annually for 3 years. | Biological: bevacizumab<br> <br> Drug: capecitabine<br> <br> Drug: docetaxel<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Confirmed tumor response (complete or partial) rate as measured by RECIST |  | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  | Up to 5 years | 
| Overall survival |  | Up to 5 years | 

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