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

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.

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