Capecitabine 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 capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. PURPOSE: This phase II trial is studying how well capecitabine 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 a fixed-dose of capecitabine. Secondary Determine the clinical benefit, time to treatment failure (TTF), safety, and toxicity profile of this regimen in these patients. Determine the pharmacokinetics (PK) and pharmacogenetics in these patients. Correlate pharmacodynamic effects of this drug with toxicity and response in these patients. Determine compliance and adherence to this regimen and correlate with PK parameters in these patients. OUTLINE: This is an open-label study. Patients receive a fixed-dose of oral capecitabine twice daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically. PROJECTED ACCRUAL: A total of 45 patients will be accrued for this study.

Official Title
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Phase II Study of Fixed-Dose Capecitabine in Metastatic Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: capecitabine


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed diagnosis of adenocarcinoma of the breast Evidence of metastatic involvement (stage IV disease) Patients must have measurable disease At least one measurable lesion as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) Treated brain metastases (surgery or radiation therapy) allowed if clinically stable Patients with leptomeningeal disease are ineligible Hormone receptor status: Not specified PATIENT CHARACTERISTICS: Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Male or female Menopausal status not specified Absolute neutrophil count (ANC) ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Creatinine clearance > 50 mL/min Fertile patients must use effective contraception No history of another severe and/or life-threatening medical disease No other active primary malignancy Not pregnant or nursing Negative pregnancy test Patients with asymptomatic HIV infection are eligible Liver dysfunction score ≤ 9 No pre-existing liver disease (i.e., cirrhosis or active viral hepatitis) No active gastrointestinal malabsorption illness No clinically significant cardiac disease, including the following: Congestive heart failure, symptomatic coronary artery disease, and cardiac arrhythmias not well controlled with medication, or myocardial infarction within the past six months No prior unanticipated severe reaction to fluoropyrimidine therapy, known hypersensitivity to fluorouracil, or known dihydropyrimidine dehydrogenase deficiency No history of uncontrolled seizures or central nervous system disorders No significant history of noncompliance to medical regimens No clinically significant psychiatric disability that would preclude study compliance PRIOR CONCURRENT THERAPY: No previous capecitabine Up to 3 prior cytotoxic regimens allowed for metastatic disease Prior noncytotoxic therapy allowed (e.g., hormonal treatment or trastuzumab) No other concurrent therapies intended to treat the primary condition including chemotherapy, biologic agents, or immunotherapy No concurrent anti-estrogen therapy, radiation therapy, or investigational systemic therapy No other concurrent investigational drugs No concurrent use of the following drugs: warfarin for full anticoagulation, cimetidine, or azidothymidine (AZT) Mini-dose warfarin for prophylaxis of central venous catheter thrombosis allowed At least 4 weeks since prior sorivudine or brivudine Concurrent use of bisphosphonates allowed if initiated before beginning study therapy Concurrent use of megestrol acetate suspension as an appetite stimulant allowed

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: Capecitabine<br>26 patients received the pre-defined starting dose of capecitabine of 3,000 mg orally daily given in two divided doses. Two thirds of the patients received either the same dose or a 500 mg lower dose compared to what would have been administered with a commonly used body surface area (BSA)-dosing schedule (2,000 mg/m2 with rounding down to nearest 500 mg multiple). | Drug: capecitabine<br>* A total of 115 cycles of therapy were administered and five patients did not complete cycle 1. The median number of cycles initiated was four (range 1-16).<br>* Other names: Xeloda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT/MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. | Participants were followed to progression, evaluated every 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Benefit as Assessed by Lack of Progression for at Least 24 Weeks | The overall clinical benefit rate as assessed by number of participants with lack of progression for at least 24 weeks. | 3-week cycles of treatment up to 16 cycles | 
| Pharmacokinetics of Capecitabine and Metabolites as Assessed by Maximum Plasma Concentration | Pharmacokinetics of Capecitabine and metabolites [5-fluoro-5'-deoxycytidine (5'-DFCR), 5-fluoro-5'-dexoxyuridine (5'-DFUR), and 5-fluorouracil (FU)] assessed using maximum plasma concentration (Cmax) in ng/mL. | 0.25, 0.5, 1, 2, 3, 4, 5, 6 and 8 hours | 
| Pharmacokinetics of Capecitabine and Metabolites as Assessed by Area Under the Curve (AUC) | Pharmacokinetics of Capecitabine and metabolites [5-fluoro-5'-deoxycytidine (5'-DFCR), 5-fluoro-5'-dexoxyuridine (5'-DFUR), and 5-FU] assessed using AUC in ng*h/mL. | 0.25, 0.5, 1, 2, 3, 4, 5, 6 and 8 hours | 
| Adherence and Compliance to Oral Medication Using Electronic Monitoring | This was assessed by number of participants who did not miss any doses of Capecitabine during treatment using the Medication Event Monitoring System (MEMS). | 3-week cycles of treatment up to 16 cycles | 
| Time to Treatment Failure | Time to treatment failure in weeks | 3-week cycles of treatment up to 16 cycles | 

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