Combination Chemotherapy in Treating Patients With Metastatic Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. Drugs such as mesna may be effective in preventing some of the side effects of chemotherapy. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy consisting of etoposide and ifosfamide given with mesna, and cisplatin in treating patients who have metastatic breast cancer.

Detailed Description
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OBJECTIVES: Determine the objective response rate in patients with metastatic breast cancer treated with etoposide, ifosfamide with mesna, and cisplatin. Determine the tolerability and toxicity of this regimen in these patients. OUTLINE: Patients are stratified according to number of prior chemotherapy courses for metastatic disease (0 vs 1). Patients receive etoposide IV over 60-90 minutes, cisplatin IV over 30 minutes, and ifosfamide IV over 30 minutes on days 1-3. Mesna is administered IV over 15 minutes 30 minutes prior to and 4 hours after ifosfamide, then orally at 8 hours post infusion. Treatment continues every 28 days in the absence of unacceptable toxicity or disease progression. Patients are followed every 3 months. PROJECTED ACCRUAL: At least 36 patients (16 per stratum) will be accrued over 36 months.

Official Title
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A Phase II Study Of An OutPatient Three Day VIP Regimen With Oral Mesna For Metastatic Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: cisplatin
* Drug: etoposide
* Drug: ifosfamide
* Drug: Mesna


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically proven progressive metastatic breast cancer Measurable disease Any lesion measurable in 2 dimensions Hepatic metastases if the sum of the measurements below the costal margin in the midclavicular line and the tip to the xiphoid process is greater than 5 cm during quiet respiration Hepatic defects that are clearly measurable by radionuclide, CAT, or MRI scans Bone metastases are not considered measurable disease Evaluable disease allowed if measurable disease also present No brain metastases, carcinomatous meningitis, or spinal cord compression Hormone receptor status: Not specified PATIENT CHARACTERISTICS: Age: Not specified Menopausal status: Not specified Performance status: ECOG 0-2 Life expectancy: At least 3 months Hematopoietic: Hemoglobin at least 10 g/dL WBC at least 4,000/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 2.0 mg/dL Renal: Creatinine no greater than 1.5 mg/dL No bladder outlet obstruction Cardiovascular: No symptomatic cardiovascular disease (e.g., congestive heart disease) or inability to tolerate a fluid load Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No active infection No prior malignancies except adequately treated basal or squamous cell skin cancer or carcinoma in situ of the cervix PRIOR CONCURRENT THERAPY: Biologic therapy: No greater than 1 prior biologic response modifier treatment for metastatic disease Chemotherapy: No greater than 1 prior chemotherapy regimen for metastatic disease allowed Patients who relapsed during or within 6 months after adjuvant chemotherapy are considered to have failed 1 regimen Patients who relapsed more than 6 months after adjuvant chemotherapy are considered to not have had a prior regimen Greater than 4 weeks since prior chemotherapy (greater than 6 weeks for mitomycin or nitrosoureas) and recovered No prior cisplatin, etoposide, or ifosfamide Endocrine therapy: Prior medical or surgical hormonal therapy allowed Radiotherapy: Prior radiation therapy to areas of measurable disease allowed if indicator lesion increased in size by greater than 25% after treatment Recovered from effects of prior radiotherapy Surgery: Recovered from effects of major surgery Other: At least 7 days since prior nephrotoxic drugs (e.g., aminoglycosides, diuretics, lithium, intravenous contrast, or nonsteroidal antiinflammatory drugs)
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

| Intervention/Treatment |
| --- |
|Drug: cisplatin|cisplatin IV over 30 minutes on days 1-3.|
|Drug: etoposide|etoposide IV over 60-90 minutes on days 1-3.|
|Drug: ifosfamide|ifosfamide IV over 30 minutes on days 1-3.|
|Drug: Mesna|Mesna is administered IV over 15 minutes 30 minutes prior to and 4 hours after ifosfamide, then orally at 8 hours post infusion.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the objective response rate in patients with metastatic breast cancer treated with etoposide, ifosfamide with mesna, and cisplatin. |  | Treatment continues every 28 days in the absence of unacceptable toxicity or disease progression. | 

 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