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

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.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label

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.

Primary:

• Time to progression No

Secondary:

• Response rate as measured by prostate-specific antigen and objective parameters No
• Frequency of grades 3-4 toxicity Yes
• Pattern of immune response as measured by immunohistochemistry No

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

Lead Sponsor: UCSF Helen Diller Family Comprehensive Cancer Center

UCSF Comprehensive Cancer Center

San Francisco California 94115 United States

Veterans Affairs Medical Center - San Francisco

San Francisco California 94121 United States

Overall Clinical Trial Officials and Contacts

Charles Ryan, MD Study Chair UCSF Helen Diller Family Comprehensive Cancer Center  

Information obtained from ClinicalTrials.gov on July 23, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00309894

Study ID Number: CDR0000456193

ClinicalTrials.gov Identifier: NCT00309894

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database