Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Closed	Not specified	NCI	UCSF-035516 UCSF-H45860-23833-02, NCT00309894

Objectives

Primary

1. 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

1. Evaluate the objective response frequency in patients treated with this regimen.
2. Investigate the safety of this regimen.

Entry 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

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

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

Expected Enrollment

A total of 48 patients will be accrued for this study.

Outcomes

Time to progression

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

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.

Trial Contact Information

Trial Lead Organizations

UCSF Helen Diller Family Comprehensive Cancer Center

Charles Ryan, MD, Protocol chair		Ph: 415-353-9279; 800-888-8664 Email: ryanc@medicine.ucsf.edu

Registry Information
Official Title		Phase II Trial to Assess the Activity of Ketoconazole Plus GM-CSF in Patients with Prostate Cancer Progressive After Androgen Deprivation
Trial Start Date		2006-06-12
Registered in ClinicalTrials.gov		NCT00309894
Date Submitted to PDQ		2005-10-12
Information Last Verified		2007-04-16
NCI Grant/Contract Number		CA82103

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