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

Condition(s) targeted: Prostate Cancer

Intervention: ketoconazole (Drug); sargramostim (Drug); therapeutic hydrocortisone (Drug)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: UCSF Helen Diller Family Comprehensive Cancer Center

Official(s) and/or principal investigator(s):
Charles Ryan, MD, Study Chair, Affiliation: UCSF Helen Diller Family Comprehensive Cancer Center

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.

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

Study design: Treatment, Non-Randomized, Open Label

Primary outcome: Time to progression

Secondary outcome:

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

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.

Minimum age: N/A. Maximum age: N/A. Gender(s): Male.

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

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

UCSF Comprehensive Cancer Center, San Francisco, California 94115, United States

Veterans Affairs Medical Center - San Francisco, San Francisco, California 94121, United States

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

Starting date: June 2006
Last updated: May 23, 2008