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

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

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.

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.

Intervention(s) in this Clinical Trial

• Dietary Supplement: calcitriol
  • IV
• Drug: dexamethasone
  • Oral
• Genetic: protein expression analysis
  • Correlative Study
• Other: laboratory biomarker analysis
  • Correlative Study

Primary Measures

• Objective response (complete or partial response)
  • Time Frame: 1 year
    Safety Issue?: No

Secondary Measures

• Expression of VDR and CYP24 in peripheral blood mononuclear cells as assessed at baseline and on days 2 and 3
  • Time Frame: 1 year
    Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Roswell Park Cancer Institute Other

Overall Clinical Trial Officials and Contacts

Donald L. Trump, MD Principal Investigator Roswell Park Cancer Institute  

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00524589

Study ID Number: CDR0000563197

ClinicalTrials.gov Identifier: NCT00524589

Health Authority: United States: Institutional Review Board