Official Title: “A Pilot Trial of Calcitriol in Localized Prostate Cancer: Investigation of Biologic Effects and Potential Intermediate Endpoints”

RATIONALE: Calcitriol and dexamethasone may slow the growth of prostate cancer cells.

PURPOSE: This randomized phase II trial is studying how well giving calcitriol together with dexamethasone before radical prostatectomy works in treating patients with localized stage II or stage III adenocarcinoma (cancer) of the prostate.

Study Type: Interventional

Study Design: Treatment, Randomized, Active Control

Study Primary Completion Date: December 2011

OBJECTIVES: - Determine the effect of calcitriol and dexamethasone before radical prostatectomy on tumor vessel density in patients with localized adenocarcinoma of the prostate. - Determine the effect of this regimen on the extent of prostatic intraepithelial neoplasia in these patients. - Determine the effect of this regimen on the expression of apoptosis markers, p21, p27, prostate-specific antigen (PSA), prostate-specific membrane antigen, and VDR expression in tumor-associated vascular endothelial cells and endothelium derived from normal-appearing prostate and tumor in these patients. - Determine the acute effects of this regimen on serum PSA in these patients. - Determine the toxicity of this regimen in these patients.

OUTLINE: This is a two-stage, randomized, pilot study. - Stage 1: Patients are randomized to 1 of 2 treatment arms. - Arm I: Patients receive oral dexamethasone once daily on days 1-4 and oral calcitriol once daily on days 2-4 weekly for 4 weeks before surgery.

Within 48 hours of the last dose, patients undergo radical prostatectomy. - Arm II: Patients receive no study drugs, but undergo radical prostatectomy. - Stage 2: If sufficient activity is seen with the dexamethasone and calcitriol regimen in stage 1, the study is expanded and additional patients are randomized to 1 of 4 treatment arms. - Arm I: Patients receive dexamethasone and calcitriol as in stage 1, arm I. - Arm II: Patients receive oral dexamethasone once daily on days 1-4. - Arm III: Patients receive oral calcitriol once daily on days 2-4. - Arm IV: Patients undergo radical prostatectomy as in stage 1, arm II. In arms I, II, and III, patients undergo radical prostatectomy as in stage 1, arm I.

Patients are followed at 1, 3, and 12 months.

PROJECTED ACCRUAL: A total of 20-80 patients (20 for stage 1 [10 per treatment arm] and 60 for stage 2) will be accrued for this study within 2 years.

Intervention(s) in this Clinical Trial

• Dietary Supplement: calcitriol
  • Given orally
• Drug: dexamethasone
  • Given orally
• Procedure: observation
  • No intervention before surgery

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Stage 1, Arm I
  • Patients receive oral dexamethasone once daily on days 1-4 and oral calcitriol once daily on days 2-4 weekly for 4 weeks before surgery.
• No Intervention: Stage 1, Arm II
  • No study drugs before surgery.
• Experimental: Stage 2, Arm I
  • Patients receive dexamethasone and calcitriol as in stage 1, arm I.
• Experimental: Stage 2, Arm II
  • Patients receive oral dexamethasone once daily on days 1-4.
• Experimental: Stage 2, Arm III
  • Patients receive oral calcitriol once daily on days 2-4.
• Experimental: Stage 2, Arm IV
  • Patients do not receive study drugs before surgery as in stage 1, arm II.

Primary Measures

• Effect of preoperative high-dose calcitriol and dexamethasone on prostatic tumor vessel density measured at 1, 2, 3, and 12 months post prostatectomy
  • Safety Issue?: No

Secondary Measures

• Effect of preoperative high-dose calcitriol and dexamethasone on extent of prostatic intraepithelial neoplasia (PIN) at 1, 2, 3, and 12 months post prostatectomy
  • Safety Issue?: No

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the prostate
• Organ-confined disease
• cT1, cT2, or cT3 tumors
• Patients with cT1 tumors are eligible if ≥ 1 core biopsies have ≥ 50% of the tumor OR if 50% of the cores examined contain the tumor
• No small cell carcinoma of the prostate
• Scheduled for radical prostatectomy

PATIENT CHARACTERISTICS:

• Age
• 18 and over
• Performance status
• Not specified
• Life expectancy
• Not specified
• Hematopoietic
• Platelet count ≥ 100,000/mm^3
• WBC ≥ 3,500/mm^3
• Hepatic
• ALT and AST ≤ 4 times normal
• Bilirubin ≤ 2 mg/dL
• Renal
• Creatinine ≤ 2 times upper limit of normal
• Calcium ≤ 10.5 mg/dL
• No detectable renal stones by CT scan or ultrasound
• Other
• No history of diabetes mellitus requiring pharmacotherapy

PRIOR CONCURRENT THERAPY:

• Biologic therapy
• Not specified
• Chemotherapy
• Not specified
• Endocrine therapy
• More than 5 years since prior antiestrogens, antiandrogens, luteinizing hormone-releasing hormone agonists, estrogen, or progestational agents
• Radiotherapy
• Not specified
• Surgery
• See Disease Characteristics
• No prior nephrectomy
• No prior prostatic surgery
• No prior cryotherapy or transurethral resection of the prostate

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Roswell Park Cancer Institute

Overall Clinical Trial Officials and Contacts

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

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00084864

Study ID Number: CDR0000365693

ClinicalTrials.gov Identifier: NCT00084864

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database