Imatinib Mesylate in Treating Patients With Metastatic Breast Cancer

Study Overview
=================
Brief Summary
-----------------
Phase II trial to study the effectiveness of imatinib mesylate in treating patients who have metastatic breast cancer. Imatinib mesylate may stop the growth of cancer by blocking the enzymes necessary for tumor cell growth

Detailed Description
-----------------
PRIMARY OBJECTIVES: I. To determine the efficacy of STI571 in metastatic breast cancer (MBC) that demonstrates expression of CD117 (c-kit) and/ or PDGFR. SECONDARY OBJECTIVES: I. To determine the clinical activity of STI571 in MBC with expression of CD117 (ckit) and/ or PDGFR by evaluating progression-free survival (PFS). II. To determine the toxicity profile and tolerability of STI571 in patients with MBC. III. To define serum, tissue and imaging surrogate endpoints of activity of STI571 in MBC. OUTLINE: Patients receive oral imatinib mesylate twice daily. Treatment continues for at least 8 weeks in the absence of disease progression or unacceptable toxicity.

Official Title
-----------------
Phase II Trial of STI571 in Metastatic Breast Cancer

Conditions
-----------------
Male Breast Cancer, Recurrent Breast Cancer, Stage IV Breast Cancer

Intervention / Treatment
-----------------
* Drug: imatinib mesylate
* Other: laboratory biomarker analysis


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically or cytologically confirmed metastatic breast cancer Documented expression of CD117 (c-kit) or platelet-derived growth factor receptor Adequate tumor tissue from either the primary tumor and/or metastatic disease available for evaluation Must have received prior chemotherapy with an anthracycline (doxorubicin or epirubicin) and/or taxane (paclitaxel or docetaxel) as adjuvant or for advanced disease At least 1 unidimensionally measurable lesion At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan Bone disease may not be only source of measurable disease Pleural or peritoneal ascites are not considered measurable disease No known brain metastases Hormone receptor status: Not specified Female or male Not specified Performance status - ECOG 0-2 Performance status - Karnofsky 60-100% More than 12 weeks Absolute neutrophil count at least 1,500/mm^3 WBC at least 3,000/mm^3 Platelet count at least 100,000/mm^3 Bilirubin normal AST or ALT no greater than 2.5 times upper limit of normal Creatinine normal Creatinine clearance at least 60 mL/min No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia No other uncontrolled concurrent illness No ongoing or active infection No prior allergic reaction attributed to compounds of similar chemical or biologic composition to imatinib mesylate No other malignancy within the past 5 years except basal cell skin cancer or carcinoma in situ of the cervix No psychiatric illness or social situation that would preclude study compliance Not pregnant or nursing Negative pregnancy test Fertile patients must use effective barrier contraception during and for 1 week after study No concurrent biologic agents No more than 2 prior chemotherapy regimens for metastatic disease Therapy with high-dose regimens or bone marrow transplantation considered 1 regimen At least 4 weeks since prior chemotherapy (6 weeks for carmustine or mitomycin) and recovered No concurrent chemotherapy Prior hormonal therapy for stage IV disease and/or as adjuvant therapy allowed At least 4 weeks since prior radiotherapy and recovered Prior localized radiotherapy that does not influence the signal of the evaluable lesion is allowed At least 2 weeks since prior minor surgery At least 4 weeks since prior major surgery Recovered from prior surgery Low-molecular weight heparin or heparin allowed for anticoagulation No concurrent warfarin No concurrent combination antiretroviral therapy for HIV-positive patients No concurrent investigational therapies or agents No other concurrent anticancer therapy No concurrent intake of cola, orange juice, grapefruit, or orange or grapefruit sections

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

Sexes Eligible for Study
-----------------
All

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: Treatment (imatinib mesylate)<br>Patients receive oral imatinib mesylate twice daily. Treatment continues for at least 8 weeks in the absence of disease progression or unacceptable toxicity. | Drug: imatinib mesylate<br>* Given PO<br>* Other names: Glivec;Other: laboratory biomarker analysis<br>* Optional correlative studies<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective tumor response (CR + PR), as determined by the RECIST criteria |  | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events |  | Up to 2 years | 
| Time to progression | Reported using the Kaplan-Meier method with 95% confidence intervals indicated. | Up to 2 years | 
| Overall survival | Reported using the Kaplan-Meier method with 95% confidence intervals indicated. | Up to 2 years |