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

This study has been completed.
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 [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Response rate as measured by prostate-specific antigen and objective parameters [ Designated as safety issue: No ]
  • Frequency of grades 3-4 toxicity [ Designated as safety issue: Yes ]
  • Pattern of immune response as measured by immunohistochemistry [ Designated as safety issue: No ]

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.


Genders 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
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
Study Chair: Charles Ryan, MD University of California, San Francisco
  More Information

Additional Information:
No publications provided

Responsible Party: University of California, San Francisco Identifier: NCT00309894     History of Changes
Other Study ID Numbers: CDR0000456193, UCSF-035516, UCSF-H45860-23833-02
Study First Received: March 29, 2006
Last Updated: October 9, 2012
Health Authority: United States: Federal Government

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
Cortisol succinate
Hydrocortisone acetate
Hydrocortisone 17-butyrate 21-propionate
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Dermatologic Agents
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antifungal Agents
Anti-Infective Agents processed this record on April 23, 2014