Ketoconazole, Hydrocortisone, and GM-CSF in Treating Patients With Progressive Prostate Cancer After Hormone Therapy

• Status: Completed
• Trial end date: 2007-12-01
• Target enrollment: 0
• Participant gender: Male

Summary

RATIONALE: Androgens can cause the growth of prostate cancer cells. Drugs, such as ketoconazole, may stop the adrenal glands from making androgens. GM-CSF may help ketoconazole work better by making tumor cells more sensitive to the drug. Giving ketoconazole together with hydrocortisone and GM-CSF may be an effective treatment for prostate cancer.

PURPOSE: This phase II trial is studying how well giving ketoconazole together with hydrocortisone and GM-CSF works in treating patients with progressive prostate cancer after hormone therapy.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of California, San Francisco
• Collaborator: National Cancer Institute (NCI)
• Treatments: Cortisol succinate; Hydrocortisone; Hydrocortisone 17-butyrate 21-propionate; Hydrocortisone acetate; Hydrocortisone hemisuccinate; Ketoconazole; Sargramostim

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the prostate

• Progressive disease after androgen deprivation AND meets 1 of the following criteria:

• Measurable disease

• Measurable lesions ≥ 10 mm with spiral CT

• Up to 5 lesions per organ and 10 lesions total should be identified as target lesions

• No measurable disease

• Patients with prostate-specific antigen (PSA)-only disease must have an elevated PSA

• PSA evidence for progressive disease consists of a PSA level of ≥ 5 ng/mL that has risen on ≥ 2 successive occasions, ≥ 2 weeks apart

• Patients with a positive bone scan must also have an elevated PSA

• Patients who received prior antiandrogen as a part of primary androgen ablation therapy must demonstrate disease progression after discontinuation of the antiandrogen

• Disease progression after antiandrogen withdrawal is defined as 2 consecutive rising PSA values obtained ≥ 2 weeks apart, or documented osseous or soft tissue progression

• Patients receiving flutamide must have had ≥ 1 of the PSA values obtained ≥ 4 weeks after flutamide discontinuation

• Patients receiving bicalutamide or nilutamide must have had ≥ 1 of the PSA values obtained ≥ 6 weeks after antiandrogen discontinuation

• Testosterone < 50 ng/dL

• PSA ≥ 5 ng/mL

PATIENT CHARACTERISTICS:

• Karnofsky performance status 60-100%

• No serious intercurrent infections or nonmalignant uncontrolled medical illnesses

• No psychiatric illnesses OR social situations that would limit compliance

• No active or uncontrolled autoimmune disease

• ALT and AST normal

• Bilirubin normal

• Absolute neutrophil count ≥ 1,500/mm³

• Platelet count ≥ 100,000/mm³

• Creatinine ≤ 1.5 times upper limit or normal (ULN)

• Hemoglobin ≥ 8 g/dL

• No other currently active malignancy except for nonmelanoma skin cancer

• No currently active malignancy defined as therapy completed with ≤ 30% risk of relapse

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• Patients must continue primary androgen deprivation therapy with a luteinizing-hormone releasing-hormone (LHRH) analogue if they have not undergone orchiectomy

• No prior systemic chemotherapy for prostate cancer

• All other systemic chemotherapy must have been completed ≥ 2 years prior to study

• No other concurrent chemotherapy, immunotherapy, or radiotherapy

• Major surgery or radiation therapy completed ≥ 4 weeks prior to study

• No other concurrent corticosteroids, including routine use antiemetics

• No prior ketoconazole, aminoglutethimide, or corticosteroids for treatment of progressive prostate cancer

• No prior immunotherapy (e.g., vaccines or sargramostim GM-CSF)

• Patients receiving any other hormonal therapy (e.g., megestrol, finasteride, herbal product known to decrease PSA levels [e.g., saw palmetto or PC-SPES], or any systemic corticosteroid) must discontinue the agent ≥ 4 weeks prior to enrollment and progressive disease must be documented after discontinuation

• No initiation of bisphosphonate therapy within 1 month prior to starting study therapy

• Patients on stable doses that show tumor progression are allowed to continue bisphosphonate

• No concurrent supplements or complementary medicines/botanicals, except any combination of the following:

• Conventional multivitamin supplements

• Selenium

• Lycopene

• Soy supplements

• Vitamin E

• At least 8 weeks since prior radiopharmaceuticals (strontium chloride Sr 89, samarium Sm 153 lexidronam pentasodium)

• No other concurrent investigational or commercial anticancer agents or therapies