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