OBJECTIVES:

• Determine the maximum tolerated dose of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010) administered with sargramostim (GM-CSF) in patients with metastatic androgen-independent prostate cancer.
• Determine the safety of this regimen in these patients.
• Determine the T-cell immunity and T-cell response in patients treated with this regimen.
• Determine the pharmacokinetics of MDX-010 in these patients.
• Determine the prostate-specific antigen and/or objective responses in patients treated with this regimen.

OUTLINE: This is a multicenter, dose-escalation study of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010).

Patients receive MDX-010 IV over 90 minutes on day 1 and sargramostim (GM-CSF) subcutaneously on days 1-14. Treatment repeats every 28 days for a total of 4 courses. GM-CSF continues beyond 4 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of MDX-010 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed at 30 days.

PROJECTED ACCRUAL: A total of 12-24 patients will be accrued for this study within 6-7 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed prostate cancer

  • Metastatic disease

• Progressive disease after prior androgen deprivation as defined by at least 1 of the following criteria:

  • Patients with measurable disease must have an increase of at least 20% in the sum of the longest diameter of target lesions OR the appearance of 1 or more new lesions

  • Patients with nonmeasurable disease must have a positive bone scan and a prostate-specific antigen (PSA) level of at least 5 ng/mL, which has risen on at least 2 successive occasions at least 2 weeks apart*

    • At least 1 PSA level must be obtained at least 4 weeks after flutamide (6 weeks after bicalutamide or nilutamide) NOTE: *An additional PSA level is required if the confirmatory PSA is not greater than the screening PSA

• Testosterone no greater than 50 ng/dL

  • Patients with no prior orchiectomy must continue luteinizing hormone-releasing hormone agonist therapy
• No history or radiologic evidence of CNS metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 12 weeks

Hematopoietic

• Absolute neutrophil count greater than 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 8 g/dL

Hepatic

• Bilirubin less than 1.5 times upper limit of normal (ULN)
• SGOT and SGPT no greater than 2.5 times ULN

Renal

• Creatinine no greater than 1.5 times ULN

Cardiovascular

• No significant cardiovascular disease
• No New York Heart Association class III or IV congestive heart failure
• No active angina pectoris
• No myocardial infarction within the past 6 months

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception prior to, during, and for 3 months after study participation

• No history of autoimmune disease including, but not limited to, any of the following:

  • Systemic lupus erythematosus
  • Rheumatoid arthritis
  • Inflammatory bowel disease
• No other medical or psychiatric illness that would preclude study participation or giving informed consent
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or stage I or II cancer currently in complete remission

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior immunotherapy (e.g., vaccines or investigational)
• No other concurrent colony-stimulating factors

Chemotherapy

• No prior chemotherapy
• No concurrent chemotherapy

Endocrine therapy

• See Disease Characteristics
• At least 4 weeks since prior systemic corticosteroids
• At least 4 weeks since other prior hormonal therapy, including megestrol and finasteride
• No concurrent systemic steroid therapy except inhaled or topical steroids

• No other concurrent hormonal therapy

  • Hormones administered for nondisease-related conditions (e.g., insulin for diabetes) allowed

Radiotherapy

• At least 4 weeks since prior radiotherapy and recovered
• More than 8 weeks since prior radiopharmaceuticals (e.g., strontium chloride Sr 89 and samarium Sm 153 lexidronam pentasodium)
• Prior irradiation of a symptomatic lesion or one that may produce disability (e.g., unstable femur) allowed
• No concurrent palliative radiotherapy

Surgery

• See Disease Characteristics

Other

• At least 4 weeks since prior herbal products known to decrease PSA levels (e.g., PC-SPES or saw palmetto)