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

University of California San Francisco (UCSF)

Status and phase: Completed; Phase 2

Conditions: Prostate Cancer

Treatments: Drug: therapeutic hydrocortisone; Drug: ketoconazole; Biological: sargramostim

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00309894

035516

UCSF-H45860-23833-02

Details and patient eligibility

About

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.

Full 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.

Enrollment: 49 patients

Sex: Male

Ages: Under 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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