Docetaxel With or Without Imatinib Mesylate in Treating Patients With Androgen-Independent Prostate Cancer and Bone Metastases

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as docetaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Combining docetaxel with imatinib mesylate may be effective treatment for androgen-independent prostate cancer and bone metastases. PURPOSE: This randomized phase II trial is studying docetaxel and imatinib mesylate to see how well they work compared to docetaxel alone in treating patients with androgen-independent prostate cancer and bone metastases.

Detailed Description
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OBJECTIVES: Primary Compare time to progression in patients with androgen-independent prostate cancer and bone metastases treated with docetaxel with vs without imatinib mesylate. Secondary Compare the response rates in patients treated with these regimens. Compare the toxic effects of these regimens in these patients. Compare quality of life of patients treated with these regimens. OUTLINE: This is a randomized, double-blind, placebo-controlled study. Patients are stratified according to hemoglobin (< 11g/dL vs ≥ 11 g/dL), alkaline phosphatase (normal vs elevated), number of prior regimens (0 vs 1 or 2), and ECOG performance score (0 or 1 vs 2). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive docetaxel IV on days 1, 8, 15, and 22 and oral imatinib mesylate once daily on days 1-43. Arm II: Patients receive docetaxel as in arm I and oral placebo once daily on days 1-43. In both arms, courses repeat every 43 days in the absence of disease progression or unacceptable toxicity. Patients who progress on arm II may cross over to arm I. PROJECTED ACCRUAL: A total of 152 patients (76 per treatment arm) will be accrued for this study.

Official Title
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Randomized Double-Blind Phase II Trial of Docetaxel and Imatinib Versus Docetaxel and Placebo in Metastatic Androgen-Independent Prostate Cancer (AIPC) With Bone Metastases

Conditions
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Metastatic Cancer, Prostate Cancer

Intervention / Treatment
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* Drug: Docetaxel
* Drug: Imatinib Mesylate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of adenocarcinoma of the prostate Osseous metastases confirmed by radiography Lytic bone lesions considered for biopsy if there is clinical suspicion of histologic conversion to small cell carcinoma Failed prior hormonal therapy Progressive disease, as evidenced by one of the following: 2 consecutive rises in prostate-specific antigen (PSA) of at least 1 ng/mL over 4 weeks Increase of 25% of the product of bidimensional disease or 30% in maximum diameter Increase in number of osseous metastases by bone scan Worsening symptoms attributable to disease progression (e.g., worsening bony pain) PSA ≥ 1 ng/mL Castrate serum testosterone ≤ 50 ng/dL Concurrent luteinizing-hormone releasing-hormone analog required for medically castrated patients No small cell or sarcomatoid prostate cancers No uncontrolled CNS metastases PATIENT CHARACTERISTICS: Age Any age Performance status Eastern Cooperative Oncology Group (ECOG) 0-2 Life expectancy At least 3 months Hematopoietic Absolute granulocyte count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hepatic Bilirubin ≤ 1.5 mg/dL Aspartate aminotransferase/alanine aminotransferase (AST/ALT) ≤ 2 times upper limit of normal No chronic liver disease Renal Creatinine clearance ≥ 40 mL/min Cardiovascular No New York Heart Association class III or IV congestive heart failure No unstable angina No myocardial infarction within the past 6 months No evidence of myocardial ischemia on electrocardiogram No uncontrolled severe hypertension Pulmonary No oxygen-dependent lung disease Other HIV negative No concurrent severe infection No contraindication to corticosteroids No uncontrolled diabetes mellitus No grade 2 or greater peripheral neuropathy No other malignancy within the past 2 years except nonmelanoma skin cancer No overt psychosis, mental disability, or incompetency that would preclude giving informed consent No history of noncompliance PRIOR CONCURRENT THERAPY: Biologic therapy No concurrent immunotherapy Chemotherapy No prior taxanes No more than 2 prior chemotherapy regimens At least 30 days since prior chemotherapy and recovered No other concurrent chemotherapy Endocrine therapy See Disease Characteristics At least 4 weeks since prior flutamide or nilutamide* At least 6 weeks since prior bicalutamide* NOTE: *Unless there is evidence of interim disease progression Radiotherapy At least 90 days since prior strontium chloride Sr 89 or samarium Sm 153 lexidronam pentasodium and recovered At least 30 days since other prior radiotherapy and recovered Surgery Fully recovered from prior surgery Other No concurrent ketoconazole No concurrent warfarin
Sexes Eligible for Study
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Male

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Docetaxel + Imatinib Mesylate<br>Docetaxel 30 mg/m^2 intravenous over 60 minutes on days 1, 8, 15, and 22 in 42-day cycles, with daily oral 600 mg imatinib mesylate. | Drug: Docetaxel<br> <br> * Other names: taxotere;Drug: Imatinib Mesylate<br> <br> * Other names: NSC-716051;|
| Placebo Comparator: Docetaxel + Placebo<br>Docetaxel 30 mg/m^2 intravenous (IV) over 60 minutes on days 1, 8, 15, and 22 in 42-day cycles, with daily oral placebo. | Drug: Docetaxel<br> <br> * Other names: taxotere;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression |  | Baseline to 3 years, or until disease progression | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate |  | Up to 3 years | 
| Toxic effects |  | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the prostate, recurrent prostate cancer, stage IV prostate cancer, bone metastases