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

This study has been completed.
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of California, San Francisco Identifier:
First received: March 29, 2006
Last updated: October 9, 2012
Last verified: October 2012

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.

Condition Intervention Phase
Prostate Cancer
Biological: sargramostim
Drug: ketoconazole
Drug: therapeutic hydrocortisone
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial to Assess the Activity of Ketoconazole Plus GM-CSF in Patients With Prostate Cancer Progressive After Androgen Deprivation

Resource links provided by NLM:

Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Time to progression

Secondary Outcome Measures:
  • 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

Enrollment: 49
Study Start Date: April 2004
Study Completion Date: December 2007
Primary Completion Date: November 2007 (Final data collection date for primary outcome measure)
Detailed Description:



  • 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.


  • 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.


Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No


  • 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


  • 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


  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00309894

United States, California
UCSF Comprehensive Cancer Center
San Francisco, California, United States, 94115
Veterans Affairs Medical Center - San Francisco
San Francisco, California, United States, 94121
Sponsors and Collaborators
University of California, San Francisco
National Cancer Institute (NCI)
Study Chair: Charles Ryan, MD University of California, San Francisco
  More Information

Responsible Party: University of California, San Francisco Identifier: NCT00309894     History of Changes
Other Study ID Numbers: CDR0000456193
Study First Received: March 29, 2006
Last Updated: October 9, 2012

Keywords provided by University of California, San Francisco:
adenocarcinoma of the prostate
recurrent prostate cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Hydrocortisone 17-butyrate 21-propionate
Cortisol succinate
Hydrocortisone acetate
Anti-Inflammatory Agents
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP3A Inhibitors processed this record on April 28, 2017