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

NCT ID: NCT00309894

Last Updated: 2019-08-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 49 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-04-30
• Study Completion Date: 2007-12-31

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.

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.

Conditions

Prostate Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

sargramostim

Intervention Type: BIOLOGICAL

ketoconazole

Intervention Type: DRUG

therapeutic hydrocortisone

Intervention Type: DRUG

Eligibility Criteria

Inclusion 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

• Maximum Eligible Age: 120 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Charles Ryan, MD

Role: STUDY_CHAIR

University of California, San Francisco

Locations

UCSF Comprehensive Cancer Center

San Francisco, California, United States

Veterans Affairs Medical Center - San Francisco

San Francisco, California, United States

Countries

United States

Other Identifiers

UCSF-H45860-23833-02

Identifier Type: -

Identifier Source: secondary_id

035516

Identifier Type: -

Identifier Source: org_study_id