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

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Drugs used in chemotherapy, such as capecitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining imatinib mesylate with capecitabine may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving imatinib mesylate together with capecitabine works in treating women with progressive stage IV breast cancer.

Detailed Description
-----------------
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.

Official Title
-----------------
Phase II Trial Of Imatinib Mesylate (Gleevec®) (NSC-716051) In Combination With Capecitabine (Xeloda®) (NSC-712807) In Metastatic Breast Cancer

Conditions
-----------------
Breast Cancer

Intervention / Treatment
-----------------
* Drug: Capecitabine
* Drug: Imatinib mesylate


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Imatinib Mesylate & Capecitabine<br> | Drug: Capecitabine<br>* 1,000 mg/m^2 by mouth twice daily Days 1-14 of each 21 day cycle<br>* Other names: Xeloda;Drug: Imatinib mesylate<br>* 400 mg by mouth daily<br>* Other names: Gleevec;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Confirmed Response Rate (Complete and Partial) | Number of participants with confirmed complete or partial response. Confirmed response (complete and partial) per Response Evaluation Criteria in Solid Tumors (RECIST) Criteria (V1.0). Complete Response (CR) is complete disappearance of all measurable and non-measurable disease; no new lesions; no disease related symptoms; and normalization of markers and other abnormal lab values. Partial response (PR) applies only to patients with at least one measurable lesion. PR is greater than or equal to 30% decrease under baseline of the sum of longest diameter of all target measurable lesions; no unequivocal progression of non-measurable disease and no new lesions. Confirmed response is two or more objective statuses a minimum of four weeks apart documented before progression or symptomatic deterioration. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival at 6 Months | Percentage of participants progression-free at 6 months. Progression-free survival (PFS) measured from date of registration to first observation of progressive disease (per RECIST criteria (V1.0)), death due to any cause, or symptomatic deterioration. Kaplan-Meier was used to estimate progression-free survival (PFS) at six months. | Six months | 
| Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Adverse Events (AEs) are reported by the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 3.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5= Fatal. Only adverse events that are possibly, probably or definitely related to study drug are reported. | Every 3 weeks while on treatment for up to 3 years. | 

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