RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing
so they stop growing or die.
PURPOSE: Randomized phase II trial to determine the effectiveness of CCI-779 in treating
patients who have progressive prostate cancer.
OBJECTIVES: I. Determine the safety of CCI-779 in patients with androgen-independent
prostate cancer. II. Determine the effects of CCI-779 on prostate-specific antigen levels in
these patients. III. Assess the pharmacokinetic parameters of CCI-779 in these patients. IV.
Assess the possible pharmacodynamic relationship of CCI-779 with clinical response in these
patients. V. Determine the impact of CCI-779 on the quality of life in these patients.
OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients
are randomized to 1 of 4 arms. Arm I: Patients receive low-dose CCI-779 IV over 30 minutes
weekly. Arm II: Patients receive high-dose CCI-779 IV over 30 minutes weekly. Arm III:
Patients receive low-dose placebo IV over 30 minutes weekly. Arm IV: Patients receive
high-dose placebo IV over 30 minutes weekly. Treatment continues in the absence of disease
progression or unacceptable toxicity. Patients who develop progressive disease while
receiving placebo may cross over to the equivalent dose of CCI-779. Quality of life is
assessed at baseline; at weeks 4, 8, 12, 24, and 36; and at final/cross-over visit. Patients
are followed every 3 months.
PROJECTED ACCRUAL: Approximately 150 patients will be accrued for this study.
DISEASE CHARACTERISTICS: Histologically confirmed asymptomatic, progressive, metastatic
adenocarcinoma of the prostate Progressive disease defined as increasing prostate-specific
antigen (PSA) levels from 2 measurements at least 2 weeks apart PSA greater than 5 ng/mL
Continued medical means of gonadal ablation (e.g., luteinizing hormone releasing hormone
(LHRH)) required No known CNS metastases unless previously treated by surgery or
radiotherapy and stable, asymptomatic, and not requiring steroids and anticonvulsants
PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: At
least 6 months Hematopoietic: Absolute neutrophil count at least 1,500/mm3 Platelet count
at least 100,000/mm3 Hemoglobin at least 8.5 g/Dl Hepatic: Bilirubin no greater than 1.5
times upper limit of normal (ULN) AST no greater than 3 times ULN (no greater than 5 times
ULN if liver metastases present) Serum cholesterol no greater than 350 mg/Dl Triglycerides
no greater than 300 mg/Dl Renal: Creatinine no greater than 1.5 times ULN Cardiovascular:
No unstable angina or life-threatening ventricular arrhythmia requiring maintenance
therapy No myocardial infarction within the past 6 months Other: No other malignancy in
past 5 years other than basal cell or squamous cell skin cancer HIV negative No active
infection Not immunocompromised No other major illness that would preclude study Fertile
patients must use effective contraception during and for 3 months after the study
PRIOR CONCURRENT THERAPY: Biologic therapy: Concurrent epoetin alfa allowed Chemotherapy:
No prior cytotoxic chemotherapy for prostate cancer No other concurrent chemotherapy
Endocrine therapy: See Disease Characteristics At least 6 weeks since prior antiandrogen
therapy At least 4 weeks since prior hormonal therapy (6 weeks for antiandrogens) for
prostate cancer other than continued LHRH agonist No concurrent systemic corticosteroids
No concurrent anticancer hormonal therapy Radiotherapy: At least 3 weeks since prior
radiotherapy No prior palliative radiotherapy to more than one site No prior strontium
chloride Sr 89 or samarium Sm 153 lexidronam pentasodium No concurrent radiotherapy
Surgery: At least 3 weeks since prior surgery Other: At least 4 weeks since prior
investigational agent No concurrent immunosuppressive agents No other concurrent
investigational agent No concurrent enzyme-inducing anticonvulsants (carbamazepine,
phenobarbital, phenytoin), ketoconazole, diltiazem, rifampin, terfenadine, cisapride,
astemizole, or pimozide No concurrent megestrol acetate for appetite Concurrent