Gemcitabine +/- Imatinib Mesylate, Patients w/Previously Treated Metastatic Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving gemcitabine together with imatinib mesylate may kill more tumor cells. PURPOSE: This randomized phase II trial is studying gemcitabine and imatinib mesylate to see how well they work compared to gemcitabine alone in treating patients with previously treated locally advanced or metastatic breast cancer.

Detailed Description
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OBJECTIVES: Primary Compare time to progression in patients with previously treated locally advanced or metastatic breast cancer treated with gemcitabine hydrochloride with vs without imatinib mesylate. Secondary Compare the efficacy of these regimens in these patients. Compare the overall survival of patients treated with these regimens. Compare the safety and tolerability of these regimens in these patients. OUTLINE: This is a multicenter, open-label, randomized study. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive gemcitabine hydrochloride IV on days 3 and 10. Arm II: Patients receive gemcitabine hydrochloride IV on days 3 and 10 and oral imatinib mesylate once daily on days 1-5 and 8-12. In both arms, treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months. PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study.

Official Title
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Randomized Phase II Trial of Gemcitabine and Imatinib Mesylate Versus Gemcitabine Alone in Patients With Previously Treated Locally Advanced or Metastatic Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: gemcitabine hydrochloride
* Drug: imatinib mesylate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed breast cancer Locally advanced or metastatic disease Disease progression after at least 1 prior chemotherapy regimen for metastatic disease No more than 2 prior chemotherapy regimens for metastatic disease (prior neoadjuvant or adjuvant treatment will not be included in determining the number of prior chemotherapy regimens) Measurable disease No known symptomatic or untreated brain metastases or carcinomatous meningitis Previously treated and clinically stable brain metastases allowed provided patient has been off steroids for > 7 days Hormone receptor status not specified PATIENT CHARACTERISTICS: Male or female Menopausal status not specified ECOG performance status 0-2 Life expectancy ≥ 3 months Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Bilirubin ≤ 1.5 times upper limit of normal (ULN) AST or ALT ≤ 2.5 times ULN Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 3 months after completion of study therapy Able to swallow oral medication No coexisting medical condition that would preclude study compliance No uncontrolled illness, including any of the following: Symptomatic congestive heart failure Unstable angina pectoris Cardiac arrhythmia requiring therapy Myocardial infarction within the past 6 months Active infection No New York Heart Association class III-IV cardiac disease No history of allergic reaction attributed to compounds of similar chemical or biologic composition to gemcitabine hydrochloride and/or imatinib mesylate No other primary malignancies within the past 5 years except for carcinoma in situ of the cervix or nonmelanoma skin cancer No known chronic liver disease (i.e., chronic active hepatitis or cirrhosis) No known HIV infection PRIOR CONCURRENT THERAPY: See Disease Characteristics Recovered from all prior therapy More than 2 weeks since prior surgery At least 2 weeks since prior hormonal therapy At least 2 weeks since prior trastuzumab (Herceptin®) At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas) At least 3 weeks since prior anti-vascular endothelial growth factor therapy More than 28 days since prior investigational agents At least 3 weeks since prior radiotherapy Must have evidence of ≥ 1 measurable target lesion outside the irradiated fields OR radiologically confirmed disease progression within the irradiated fields after completion of radiotherapy No prior imatinib mesylate for metastatic disease No prior gemcitabine hydrochloride for metastatic disease More than 6 months since prior adjuvant gemcitabine hydrochloride No other concurrent investigational or commercial agents No concurrent therapeutic anticoagulation with warfarin (e.g., Coumadin® or Coumadine®) Concurrent heparin or low-molecular weight heparin (e.g., Lovenox®) for therapeutic anticoagulation allowed Concurrent prophylactic warfarin therapy (e.g., mini-dose Coumadin® ≤ 1 mg daily) to maintain catheter patency allowed No concurrent routine chronic systemic corticosteroids No concurrent medications that would preclude study compliance

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm I (Gemcitabine Hydrochloride)<br>Patients receive gemcitabine hydrochloride IV on days 3 and 10. | Drug: gemcitabine hydrochloride<br>* Given IV<br>|
| Experimental: Arm II (Gemcitabine Hydrochloride + Imatinib)<br>Patients receive gemcitabine hydrochloride IV on days 3 and 10 and oral imatinib mesylate once daily on days 1-5 and 8-12. | Drug: gemcitabine hydrochloride<br>* Given IV<br>Drug: imatinib mesylate<br>* Given orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Progression | Sample size of 40 patients per group was needed to detect an 8 month increase in time to progression with the combination (80% power, alpha =.05, 2-sided). | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate (Complete and Partial Response) | Overall response rate was evaluated every 2 cycles (six weeks) for both groups using international criteria by the Response Evaluation Criteria in Solid Tumors (RECISTv1.0) for target lesions and were assessed by CT or MRI. Response rates were defined as 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) defined as OR=CR + PR | 5 years | 
| Overall Survival |  | 5 years | 

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