S0338, Imatinib Mesylate and Capecitabine in Treating Women With Progressive Stage IV Breast Cancer

OBJECTIVES:

• Determine the confirmed complete and partial response rate in women with progressive stage IV adenocarcinoma of the breast treated with imatinib mesylate and capecitabine.
• Determine the 6-month progression-free survival of patients treated with this regimen.
• Determine the toxicity of this regimen in these patients.
• Correlate, preliminarily, c-kit and platelet-derived growth factor receptor expression with estrogen and progesterone receptor status, response, survival, and time to disease progression in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive oral imatinib mesylate* once daily on days 1-21 and oral capecitabine twice daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

NOTE: *If the patient tolerates the starting dose of imatinib mesylate in course 1, the dose will be increased in subsequent courses.

Patients are followed every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 25-70 patients (25-45 patients with measurable disease and 25 with non-measurable disease) will be accrued for this study within 2 years.

• Histologically or cytologically confirmed adenocarcinoma of the breast
• Stage IV measurable disease
• Disease progression after at least 1, but no more than 2, prior chemotherapy regimens for metastatic disease
• Patients with hormone-sensitive tumors must have received prior hormonal therapy
• Patients with human epidermal growth factor receptor 2 (HER2)/neu-overexpressing tumors (3+ by immunohistochemistry or amplified by fluorescent in situ hybridization) should have received trastuzumab (Herceptin®) in the adjuvant or metastatic setting (unless contraindicated)
• No clinical evidence of or known brain or central nervous system (CNS) disease
• Hormone Receptor status known
• Female age 18 and over
• Performance status Zubrod 0-2
• Absolute neutrophil count > 1,500/mm^3
• Leukocyte count > 3,000/mm^3
• Platelet count > 100,000/mm^3
• Bilirubin normal
• aspartate aminotransferase (AST) / alanine aminotransferase (ALT) < 2.5 times upper limit of normal
• Creatinine normal OR Creatinine clearance > 60 mL/min
• Not pregnant or nursing
• Fertile patients must use effective contraception during and for 3 months after study participation
• No history of severe hypersensitivity reaction to compounds of similar chemical or biological composition to imatinib mesylate, capecitabine, or fluorouracil
• 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
• No prior biologic therapy (e.g., vaccines)
• No concurrent filgrastim (G-CSF) for chemotherapy-induced neutropenia
• No prior capecitabine or fluorouracil for metastatic breast cancer
• Prior hormonal therapy allowed
• More than 4 weeks since prior radiotherapy - Previously irradiated area(s) must not be the only site of disease
• More than 4 weeks since prior major surgery
• More than 4 weeks since prior therapy for breast cancer
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent investigational or commercial agents or therapies for metastatic breast cancer