Gemcitabine With or Without Imatinib Mesylate in Treating Patients With Metastatic or Unresectable Kidney 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 with gemcitabine alone in treating patients with metastatic or unresectable kidney cancer.

Detailed Description
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OBJECTIVES: Primary Compare stable disease and objective response in patients with metastatic or unresectable renal cell carcinoma treated with gemcitabine hydrochloride with or without imatinib mesylate. Secondary Evaluate the median survival, progression-free survival, and response rate in patients treated with gemcitabine hydrochloride and imatinib mesylate. Determine the qualitative and quantitative toxic effects of this regimen in these patients. Determine the expression of c-KIT and platelet-derived growth factor receptor-alpha protein expression in both tumor cells and associated endothelial cells using immunohistochemistry staining of paraffin-embedded tissue. OUTLINE: This is a randomized, multicenter study. Patients are stratified by histology (clear cell vs nonclear cell) and prior therapy (immunotherapy/chemotherapy vs targeted agents). Patients receive gemcitabine hydrochloride IV on days 3 and 10 and oral imatinib mesylate on days 1-5 and 8-12. Treatment repeats every 21 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients achieving partial or complete response after 2 courses of treatment continue treatment with gemcitabine hydrochloride and imatinib mesylate in the absence of disease progression or unacceptable toxicity. Patients with stable disease after 2 courses of treatment 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 on days 1-5 and 8-12. In both arms, treatment repeats every 21 days for at least 3 courses in the absence of disease progression or unacceptable toxicity. Available archived tumor tissue samples are obtained for immunohistochemical analysis to quantify the expression of c-KIT and platelet-derived growth factor receptor-alpha protein expression. After completion of study treatment, patients are followed every 3 months. PROJECTED ACCRUAL: A total of 100 patients will be accrued for this study.

Official Title
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A Phase II Trial of Gemzar (Gemcitabine) and Gleevec (Imatinib Mesylate) in Patients With Metastatic Renal Cell Carcinoma

Conditions
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Kidney Cancer

Intervention / Treatment
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* Drug: gemcitabine hydrochloride
* Drug: imatinib mesylate
* Genetic: gene expression analysis
* Genetic: protein expression analysis
* Other: immunohistochemistry staining method
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed renal cell carcinoma Metastatic disease OR unresectable primary tumor No known curative therapy exists Documented progressive renal cell carcinoma as defined by RECIST criteria within the past 6 months Measurable disease with ≥ 1 unidimensionally measurable lesion No known symptomatic brain metastasis or untreated brain metastases or carcinomatous meningitis Treated brain metastasis allowed provided the following criteria are met: Clinically stable More than 7 days since prior steroids PATIENT CHARACTERISTICS: ECOG performance status 0-2 Life expectancy ≥ 3 months Absolute neutrophil count ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ Bilirubin ≤ 1.5 times upper limit of normal (ULN) AST and 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 nonhormonal contraception during and for 3 months after completion of study treatment Must be able to swallow oral medication No coexisting medical condition that would preclude study compliance No history of allergic reaction to compounds of similar chemical or biological composition to gemcitabine hydrochloride and/or imatinib mesylate No uncontrolled illness that would preclude study participation No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia requiring therapy No myocardial infarction within the past 6 months No active infection No other malignancy within the past 5 years except carcinoma in situ of the cervix or nonmelanoma skin cancer No New York Heart Association class III-IV congestive heart failure No known chronic liver disease (i.e., chronic active hepatitis or cirrhosis) No known HIV positivity No significant history of noncompliance to medical regimens PRIOR CONCURRENT THERAPY: See Disease Characteristics Recovered from all prior therapy No more than 3 prior treatment regimens, including any of the following: No more than 1 prior cytotoxic therapy Immunotherapy regimens comprising interferon and/or aldesleukin Therapy with molecular targets Any combination of the above treatments to a maximum of 3 total therapies No prior gemcitabine hydrochloride for metastatic disease No prior imatinib mesylate for metastatic disease More than 2 weeks since prior major surgery At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas) At least 3 weeks since prior anti-vascular endothelial growth factor therapy At least 3 weeks since prior radiotherapy Must have evidence of ≥ 1 measurable target lesion outside the radiation fields OR radiologically confirmed disease progression within the radiation fields after completion of radiotherapy At least 28 days since prior and no other concurrent investigational or commercial agents, unless disease is rapidly progressing No concurrent therapeutic warfarin Concurrent low molecular weight heparin or heparin allowed for therapeutic anticoagulation Concurrent prophylactic warfarin therapy ≤ 1 mg daily to maintain catheter patency allowed No concurrent filgrastim (G-CSF) for prevention of neutropenia No other concurrent chemotherapy, immunotherapy, hormonal cancer therapy, radiation therapy, or cancer surgery No concurrent routine use (i.e., daily or every other day) of systemic corticosteroid therapy (in supraphysiologic doses) No concurrent medication that would preclude study compliance

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
Allocation: Randomized


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: gemcitabine hydrochloride|nan|
|Drug: imatinib mesylate|nan|
|Genetic: gene expression analysis|nan|
|Genetic: protein expression analysis|nan|
|Other: immunohistochemistry staining method|nan|
|Other: laboratory biomarker analysis|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stable disease |  |  | 
| Objective response |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median survival |  |  | 
| Progression-free survival |  |  | 
| Response rate |  |  | 
| Expression of c-KIT and platelet-derived growth factor receptor-alpha protein expression |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent renal cell cancer, clear cell renal cell carcinoma, papillary renal cell carcinoma, stage IV renal cell cancer