S0430 Cyclophosphamide and Capecitabine in Treating Women With Stage IV Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide 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 chemotherapy drug may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving cyclophosphamide together with capecitabine works in treating women with stage IV breast cancer.

Detailed Description
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OBJECTIVES: Determine the response rate (complete and partial, confirmed and unconfirmed) in women with stage IV breast cancer treated with oral cyclophosphamide and oral capecitabine. Determine the progression-free survival and overall survival of patients treated with this regimen. Determine the toxicity of this regimen in these patients. Determine the quality of life of patients treated with this regimen. OUTLINE: This is a multicenter study. Patients receive oral cyclophosphamide once daily on days 1-14 and oral capecitabine twice daily on days 8-21. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline and then at weeks 7, 13, 19, and 25. After completion of study treatment, patients are followed every 3 months for up to 2 years. PROJECTED ACCRUAL: A total of 96 patients will be accrued for this study within 4 years.

Official Title
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Phase II Trial of Simple Oral Therapy (Continuous Oral Cyclophosphamide and Capecitabine) in Patients With Metastatic Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: capecitabine
* Drug: cyclophosphamide


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed stage IV breast cancer Metastatic disease (M1) OR multiple sites of new disease that is clinically obvious metastatic disease (i.e., multiple sites of new osseous disease) Meets 1 of the following criteria: Measurable disease Non-measurable disease MUC-1 antigen level > 2 times upper limit of normal AND level has increased by 1.5 times Must have documented MUC-1 antigen level Either cancer antigen (CA) 15-3 or CA 27-29 allowed Must have received at least 1 prior hormonal therapy for metastatic disease (estogen receptor-positive patients only) No symptomatic brain or CNS metastases Previously treated brain or CNS metastasis allowed provided radiotherapy was completed ≥ 8 weeks before study entry Hormone receptor status: Not specified PATIENT CHARACTERISTICS: Age 18 and over Sex Female Menopausal status Not specified Performance status Zubrod 0-2 Life expectancy Not specified Hematopoietic No known existing uncontrolled coagulopathy Hepatic Not specified Renal Creatinine clearance > 40 mL/min Cardiovascular No congestive heart failure No symptomatic coronary artery disease No cardiac arrhythmia not well controlled with medication No myocardial infarction within the past 12 months No other clinically significant cardiac disease Gastrointestinal Able to take oral medication No uncontrolled nausea, vomiting, or diarrhea No lack of physical integrity of the upper gastrointestinal tract No malabsorption syndrome Other Not pregnant or nursing Fertile patients must use effective contraception No active infection requiring systemic therapy No prior severe reaction to fluoropyrimidines No known sensitivity to fluorouracil No known dihydropyrimidine dehydrogenase deficiency No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix PRIOR CONCURRENT THERAPY: Biologic therapy No concurrent immunotherapy or biologic therapy for breast cancer No concurrent gene therapy for breast cancer No concurrent filgrastim (G-CSF) Chemotherapy At least 14 days since prior chemotherapy and recovered No more than 2 prior chemotherapy regimens for metastatic disease No prior capecitabine for metastatic disease No prior oral cyclophosphamide for metastatic disease Prior IV cyclophosphamide allowed No other concurrent chemotherapy for breast cancer Endocrine therapy See Disease Characteristics No concurrent hormonal therapy for breast cancer Radiotherapy See Disease Characteristics At least 14 days since prior radiotherapy to non-CNS disease sites and recovered No concurrent radiotherapy for breast cancer Surgery Not specified Other Concurrent bisphosphonates allowed No concurrent full-dose warfarin Concurrent prophylactic warfarin (≤ 1 mg/day) to maintain port patency allowed No other concurrent antineoplastic therapy for breast cancer

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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: cyclophosphamide and capecitabine<br>cyclophosphamide orally days 1-14 and capecitabine orally days 15-21 for 8 cycles of 21 days each | Drug: capecitabine<br> <br> Drug: cyclophosphamide<br> <br> * Other names: cytoxan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate (Complete and Partial, Confirmed and Unconfirmed) | Complete Response (CR) is complete disappearance of all measurable and non-measurable disease. No new lesions, no disease related symptoms. Normalization of markers and other abnormal lab values. Partial Response (PR) is greater than or equal to 30% decrease under baseline of the sum of longest diameters of all target measurable lesions. No unequivocal progression of non-measurable disease. No new lesions. Confirmation of CR or PR means a repeat scan at least 4 weeks apart documented before progression or symptomatic deterioration. Progression is 20% increase in sum of longest diameters of target measurable lesions over smallest sum observed and/or unequivocal progression of non-measurable disease and/or appearance of new lesion/site or death due to disease without prior documentation of progression and without symptomatic deterioration. Symptomatic deterioration is global deterioration of health status requiring discontinuation of treatment without objective evidence of progression. | Patients assessed at least every six weeks while on protocol treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival and Overall Survival | Progression-Free Survival: From date of registration to time of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression-free are censored at last date of contact. Overall Survival: From date of registration to date of death due to any cause. Patients last known to be alive are censored at last date of contact. Progression is 20% increase in sum of longest diameters of target measurable lesions over smallest sum observed and/or unequivocal progression of non-measurable disease and/or appearance of new lesion/site or death due to disease without prior documentation of progression and without symptomatic deterioration. Symptomatic deterioration is global deterioration of health status requiring discontinuation of treatment without objective evidence of progression. | two years | 
| Toxicity | Number of patients for whom Grade 3 or higher toxicity observed during treatment. Only adverse events that are possibly, probably or definitely related to study drug are reported. | Patients assessed after each 21-day cycle for 8 cycles (24 weeks of treatment) | 

 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