Vinflunine and Capecitabine in Treating Patients With Previously Treated Metastatic Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as vinflunine and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving vinflunine together with capecitabine works in treating patients with previously treated metastatic breast cancer.

Detailed Description
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OBJECTIVES: Primary Evaluate the tumor response rate in patients with previously treated metastatic breast cancer treated with vinflunine and capecitabine. Secondary Describe the adverse event profile of this regimen in these patients. Determine the progression-free survival of patients treated with this regimen. Determine the overall survival of patients treated with this regimen. Determine the duration of response in patients treated with this regimen. Determine the time to treatment failure in patients treated with this regimen. Describe the quality of life of patients treated with this regimen. OUTLINE: This is a multicenter study. Patients receive vinflunine IV over 20 minutes on day 1 and oral capecitabine twice daily on days 1-14. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline, every other course, and at the completion of study treatment. After completion of study treatment, patients are followed periodically for up to 5 years.

Official Title
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Phase II Trial of Vinfluinine and Capecitabine in Previously Treated Metastatic Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: capecitabine
* Drug: vinflunine


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed breast cancer meeting the following criteria: Metastatic disease Previously treated with 1-2 chemotherapy regimens for metastatic disease Measurable disease, defined as ≥ 1 measurable lesion ≥ 2.0 cm by conventional techniques OR ≥ 1.0 cm by spiral CT scan No nonmeasurable disease, including any of the following: Bone lesions Leptomeningeal disease Ascites Pleural or pericardial effusion Inflammatory breast disease Lymphangitis cutis/pulmonis Abdominal masses not confirmed and followed by imaging techniques Cystic lesions Must have received ≥ 1 prior trastuzumab (Herceptin®)-containing regimen (unless there is a contraindication) if tumor is HER2 positive (3+ by immunohistochemistry or amplified by fluorescent in situ hybridization [FISH]) No CNS metastasis unless controlled by prior surgery and/or radiotherapy Controlled is defined as ≥ 2 months of no symptoms or evidence of progression Currently enrolled on clinical trial QOL N0392 Hormone receptor status not specified Hormone-positive tumor must meet at least 1 of the following criteria: Tumor refractory to hormonal therapy Heavy visceral tumor burden that requires chemotherapy for better and faster control of metastatic disease Relapsed disease during adjuvant hormonal therapy and failed first-line chemotherapy Not treated with hormonal therapy because of side effects or adverse events PATIENT CHARACTERISTICS: Male or female Menopausal status not specified ECOG performance status 0-2 Life expectancy ≥ 3 months Platelet count ≥ 100,000/mm^3 Hemoglobin > 8.0 g/dL WBC ≥ 3,000/mm^3 Absolute neutrophil count ≥ 1,500/mm^3 Bilirubin ≤ 1.5 times upper limit of normal (ULN) Alkaline phosphatase (AP), AST, and ALT must meet 1 of the following criteria: AP normal AND AST and ALT ≤ 5 times ULN AP ≤ 2.5 times ULN AND AST and ALT ≤ 1.5 times ULN AP ≤ 5 times ULN AND AST and ALT normal Creatinine clearance ≥ 30 mL/min Serum sodium normal Not pregnant or nursing No nursing during and for 30 days after completion of study therapy Negative pregnancy test Fertile patients must use effective contraception during and for 30 days after completion of study therapy No history of allergy or hypersensitivity to drug product excipients or to agents chemically similar to vinflunine and/or capecitabine No prior unanticipated severe reaction to fluoropyrimidine therapy No known hypersensitivity to fluorouracil No known dihydropyrimidine dehydrogenase deficiency No active, unresolved infection No New York Heart Association class III-IV cardiovascular disease, unstable angina, myocardial infarction within the past 6 months, or poorly controlled hypertension No preexisting neuropathy ≥ grade 2 No concurrent serious medical condition that would preclude study treatment No other stage III or IV invasive cancer within the past 3 years No lack of physical integrity of the upper gastrointestinal tract, clinically significant malabsorption syndrome, or inability to take oral medication Ability to complete questionnaires alone or with assistance PRIOR CONCURRENT THERAPY: See Disease Characteristics Prior unlimited hormonal therapy allowed in the neoadjuvant, adjuvant, or metastatic setting No major surgery, chemotherapy, or immunologic therapy within the past 4 weeks No radiotherapy within the past 4 weeks, except if to a nontarget lesion only Prior radiotherapy to a target lesion is allowed if there has been clear progression of the lesion since radiotherapy was completed If patient received single-dose radiotherapy or palliation to a nontarget lesion only, the patient may immediately proceed to study registration without waiting 4 weeks No prior fluoropyrimidines, including capecitabine, or vinca alkaloids (e.g., vinorelbine, vinblastine, vincristine, or vindesine) for metastatic breast cancer No prior radiotherapy to > 30% of bone marrow-containing areas No cimetidine, allopurinol, sorivudine, or brivudine within the past 2 weeks No ketoconazole, itraconazole, ritonavir, amprenavir, or indinavir within the past 2 weeks No concurrent treatment in another clinical trial in which investigational procedures are performed or investigational therapies are administered No concurrent trastuzumab (Herceptin®) No concurrent hormonal therapy No concurrent interleukin-11 No other concurrent chemotherapeutic agents, biologic agents, or radiotherapy No concurrent administration of any of the following: Cimetidine Allopurinol Sorivudine Brivudine Ketoconazole Itraconazole Ritonavir Amprenavir Indinavir Warfarin allowed if patient is on a stable dose and has an INR < 3.0

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: vinflunine + capecitabine<br>Patients receive vinflunine IV over 20 minutes on day 1 and oral capecitabine twice daily on days 1-14. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline, every other course, and at the completion of study treatment. After completion of study treatment, patients are followed periodically for up to 5 years. | Drug: capecitabine<br> <br> Drug: vinflunine<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Confirmed tumor response |  | Up to 10 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse event profile |  | Up to 10 years | 
| Progression-free survival |  | Up to 10 years | 
| Overall survival |  | Up to 10 years | 
| Duration of response |  | Up to 10 years | 
| Time to treatment failure |  | Up to 10 years | 
| Quality of life |  | Up to 10 years | 

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