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

Study Overview
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Brief Summary
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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.

Detailed Description
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OBJECTIVES: Primary Evaluate the effect of ketoconazole, hydrocortisone, and sargramostim (GM-CSF) on time to clinical progression in patients with prostate cancer that has progressed on primary hormonal therapy. Secondary Evaluate the objective response frequency in patients treated with this regimen. Investigate the safety of this regimen. OUTLINE: This is an open-label, nonrandomized study. Patients receive oral ketoconazole three times daily and oral hydrocortisone twice daily on days 1-28 and sargramostim (GM-CSF) subcutaneously on days 15-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. PROJECTED ACCRUAL: A total of 48 patients will be accrued for this study.

Official Title
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Phase II Trial to Assess the Activity of Ketoconazole Plus GM-CSF in Patients With Prostate Cancer Progressive After Androgen Deprivation

Conditions
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Prostate Cancer

Intervention / Treatment
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* Biological: sargramostim
* Drug: ketoconazole
* Drug: therapeutic hydrocortisone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Maximum Age: 120 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: sargramostim|nan|
|Drug: ketoconazole|nan|
|Drug: therapeutic hydrocortisone|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate as measured by prostate-specific antigen and objective parameters |  |  | 
| Frequency of grades 3-4 toxicity |  |  | 
| Pattern of immune response as measured by immunohistochemistry |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the prostate, recurrent prostate cancer