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.

Condition	Treatment or Intervention	Phase
adenocarcinoma of the prostate recurrent prostate cancer stage IV prostate cancer bone metastases	Drug: docetaxel  Drug: imatinib mesylate  Procedure: chemotherapy  Procedure: enzyme inhibitor therapy  Procedure: protein tyrosine kinase inhibitor therapy	Phase II

Further Study Details: 

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 144 patients (72 per treatment arm) will be accrued for this study within 2 years.

Genders Eligible for Study:  Both

Criteria

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

• 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
• AST and 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

Massachusetts
      Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States; Recruiting
New York
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States; Recruiting
Texas
      MD Anderson Cancer Center at University of Texas, Houston,  Texas,  77030-4009,  United States; Recruiting

Study chairs or principal investigators

Paul Mathew,  Study Chair,  M.D. Anderson Cancer Center   
Christopher Logothetis, MD,  M.D. Anderson Cancer Center   

Study ID Numbers:  CDR0000354505; MDA-ID-030008; NOVARTIS-MDA-ID-030008; MSKCC-03132; DFCI-03187; NCT00080678
Record last reviewed:  May 2004
Last Updated:  April 5, 2005
Record first received:  April 7, 2004
ClinicalTrials.gov Identifier:  NCT00080678
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08