Calcitriol and Dexamethasone in Treating Patients With Prostate Cancer That Did Not Respond to Hormone Therapy

Study Overview
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Brief Summary
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RATIONALE: Calcitriol may help prostate cancer cells become more like normal cells, and to grow and spread more slowly. Dexamethasone may help calcitriol work better by making tumor cells more sensitive to the drug. Giving calcitriol together with dexamethasone may be an effective treatment for prostate cancer that did not respond to hormone therapy . PURPOSE: This phase II trial is studying how well giving calcitriol together with dexamethasone works in treating patients with prostate cancer that did not respond to hormone therapy.

Detailed Description
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OBJECTIVES: To investigate the response rate in patients with androgen-independent prostate cancer treated with calcitriol and dexamethasone. To evaluate the toxicity of high-dose calcitriol and dexamethasone in these patients. OUTLINE: Patients receive oral dexamethasone once on days 1 and 2 and calcitriol IV over 1 hour on day 2. Treatment repeats weekly in the absence of disease progression or unacceptable toxicity. Blood samples are collected at baseline and on days 2 and 3 to assess VDR and CYP24 expression in peripheral blood mononuclear cells.

Official Title
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Phase II Study of Weekly Intravenous 1,25 Dihydroxycholecelciferol (Calcitriol) + Dexamethasone in Androgen Independent Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Dietary Supplement: calcitriol
* Drug: dexamethasone
* Genetic: protein expression analysis
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: History of androgen-independent prostate cancer Evidence of rising PSA level (with or without new lesion by radiograph or physical examination), defined as follows: PSA level > 5 ng/mL and clearly rising on 2 measurements taken ≥ 2 weeks apart after androgen deprivation therapy (i.e., orchiectomy or luteinizing hormone-releasing hormone [LHRH] analogue) and antiandrogen withdrawal, if appropriate PSA rising before and on the first value taken at 4 or 6 weeks after antiandrogen cessation is considered disease progression Measurable or evaluable disease as defined by any of the following: Measurable or evaluable tumor masses by radiograph or physical examination Evaluable PSA Concurrent LHRH analogue or diethylstilbestrol (DES) for testicular androgen suppression required if no prior bilateral orchiectomy Patients receiving other monotherapy for testicular androgen suppression must switch to a LHRH analogue or DES ≥ 14 days prior to study entry PATIENT CHARACTERISTICS: ECOG 0-2 Life expectancy ≥ 12 weeks ANC ≥ 1,000/mm³ Platelet count ≥ 75,000/mm³ Hemoglobin > 8.9 g/dL (transfusion or erythropoietin support allowed) Serum creatinine ≤ 1.8 mg/dL AST ≤ 4 times upper limit of normal (ULN) Total bilirubin ≤ 2.0 mg/dL Serum corrected calcium < ULN No history of nephrolithiasis within the past 5 years No unstable, uncontrolled peptic ulcer disease, congestive heart failure, glaucoma, HIV, or diabetes PRIOR CONCURRENT THERAPY: At least 28 days since prior androgen deprivation therapy (≥ 42 days for bicalutamide) A 28-day washout period is not required for patients who have previously progressed despite antiandrogen withdrawal and who have resumed antiandrogens without reduction of PSA At least 14 days since prior radiotherapy At least 28 days since prior strontium 89 At least 28 days since prior chemotherapy and/or investigational agents No concurrent medications or supplements that contain additional calcium (e.g., Tums) No concurrent radiotherapy for pain control or any other indication Concurrent bisphosphonates allowed provided dose/regimen is stable

Ages Eligible for Study
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Maximum Age: 120 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dexamethasone and Calcitriol<br>Patients receive oral dexamethasone once on days 1 and 2 and calcitriol IV over 1 hour on day 2. Treatment repeats weekly. | Dietary Supplement: calcitriol<br>* IV<br>Drug: dexamethasone<br>* Oral<br>Genetic: protein expression analysis<br>* Correlative Study<br>Other: laboratory biomarker analysis<br>* Correlative Study<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response (Complete or Partial Response) | 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. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Corrected Serum Calcium Expression | Number of patients with corrected serum calcium levels between 11 mg/dL and 12 mg/dL detected on 1 or more occasions. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent prostate cancer