This phase I/II trial studies the side effects and best dose of calcitriol when given in combination with ketoconazole and therapeutic hydrocortisone and to see how well it works in treating patients with prostate cancer. Calcitriol may help prostate cancer cells become more like normal cells and grow and spread more slowly. Ketoconazole and therapeutic hydrocortisone may help calcitriol work better by making tumor cells more sensitive to the drug. Giving calcitriol together with ketoconazole and therapeutic hydrocortisone may be a better treatment for prostate cancer.
PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) of oral calcitriol daily x 3 consecutive days a week in combination with oral ketoconazole (400 mg thrice daily \[TID\]) + oral hydrocortisone (20 mg AM, 10 mg PM) in men with androgen independent prostate cancer (AIPC). (Phase I) II. To estimate the prostate-specific antigen (PSA) response rate. (Phase II) SECONDARY OBJECTIVES: I. To evaluate the pharmacokinetics of the phase II dose of oral calcitriol with and without ketoconazole (400 mg TID). II. Describe any objective tumor responses to the combination of oral calcitriol and ketoconazole and hydrocortisone among patients with measurable disease using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. III. Determine toxicities and tolerability of oral calcitriol combination with daily oral ketoconazole and hydrocortisone. OUTLINE: This is a phase I, dose-escalation study of calcitriol followed by a phase II study. PHASE I: Patients receive calcitriol orally (PO) once daily (QD) on days 1-3, 8-10, 15-17, and 22-24. Patients also receive ketoconazole PO TID on days 1-24 and therapeutic hydrocortisone PO twice daily (BID) on days -1 to 24. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. PHASE II: Patients receive calcitriol and therapeutic hydrocortisone as in phase I. Patients also receive ketoconazole PO TID on days 4-24. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 30 days.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
51
Given PO
Given PO
Correlative studies
Correlative studies
Given PO
Roswell Park Cancer Institute
Buffalo, New York, United States
Determine the Maximum Tolerated Dose (MTD)
Determine the maximum tolerated dose (MTD) of oral calcitriol daily x 3 consecutive days a week in combination with oral ketoconazole (400 mg thrice daily \[TID\]) + oral hydrocortisone (20 mg AM, 10 mg PM)
Time frame: up to 11 years
PSA Response Rate
Patients will be considered evaluable for PSA response if they have at least two post-baseline PSA measurements at least 4 weeks apart, or if they have other evidence of disease progression. A PSA response will be considered a PSA decline of at least 50% must be confirmed by a second PSA value four or more weeks later. The reference PSA for these declines should be a PSA measured within 2 weeks prior to the initiation of therapy.
Time frame: Up to 11 years
Incidence of Toxicity Graded According to the National Cancer Institute CTC Version 3.0
Count of participants with serious adverse event. Please refer to the adverse event reporting for more detail.
Time frame: Up to 11 years
Objective Tumor Response, Assessed by RECIST
Judged by monthly physical exam and radiographic evaluation. Patients will be considered evaluable for tumor response if they have at least two post-baseline tumor assessments at least 4 weeks apart, received study medication for 8 weeks or if they have evidence of disease progression. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: Up to 11 years
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