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

Sponsor

University of California, San Francisco (Other)

Overall Status

Completed

CT.gov ID

NCT00309894

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Duration (Months)

24.5

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Prostate Cancer	Biological: sargramostim Drug: ketoconazole Drug: therapeutic hydrocortisone	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

49 participants

Allocation:

Non-Randomized

Masking:

None (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

Study Start Date :

Apr 1, 2004

Actual Primary Completion Date :

Nov 1, 2007

Actual Study Completion Date :

Dec 1, 2007

Outcome Measures

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 []

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 120 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCSF Comprehensive Cancer Center	San Francisco	California	United States	94115
2	Veterans Affairs Medical Center - San Francisco	San Francisco	California	United States	94121