Calcitriol and Dexamethasone Before Radical Prostatectomy in Treating Patients With Localized Adenocarcinoma (Cancer) of the Prostate

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 Overview

• Status: Terminated
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: dexamethasone; Dietary supplement: calcitriol; Other: clinical observation

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14263-0001
      • Roswell Park Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: dexamethasone; Given orally; Dietary supplement: calcitriol; Given orally
Experimental: Stage 1, Arm II; No study drugs before surgery.	Other: clinical observation; No intervention before surgery
Experimental: Stage 1 Arm 3; Patients receive oral dexamethasone once daily on days 1-4.	Drug: dexamethasone; Given orally
Experimental: Stage 1, Arm 4; Patients receive oral calcitriol once daily on days 2-4.	Dietary supplement: calcitriol; Given orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Effect of Preoperative High-dose Calcitriol and Dexamethasone on Prostatic Tumor Vessel Density Measured at 1, 2, 3, and 12 Months Post Prostatectomy	Up to 30 days of the last administration of study procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of Preoperative High-dose Calcitriol and Dexamethasone on Extent of Prostatic Intraepithelial Neoplasia (PIN) at 1, 2, 3, and 12 Months Post Prostatectomy		Up to 30 days of the last administration of study procedure
Determine the Effect of This Regimen on the Expression of Apoptosis Markers	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.	Up to 30 days of the last administration of study procedure
Determine the Acute Effects of This Regimen on Serum PSA in These Patients.		Up to 30 days of the last administration of study procedure
Number of Participants With Adverse Events, Graded According to NCI CTCAE v2.0	Number of Participants with Adverse Events, Graded According to NCI CTCAE v2.0	Up to 30 days of the last administration of study procedure

Collaborators and Investigators

• Sponsor: Roswell Park Cancer Institute
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: September 1, 2002
• Primary Completion (Actual): February 1, 2010
• Study Completion (Actual): May 1, 2010

Study Registration Dates

• First Submitted: June 10, 2004
• First Submitted That Met QC Criteria: June 10, 2004
• First Posted (Estimate): June 11, 2004

Study Record Updates

• Last Update Posted (Actual): June 12, 2017
• Last Update Submitted That Met QC Criteria: May 11, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: stage III prostate cancer; adenocarcinoma of the prostate; stage II prostate cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Micronutrients; Membrane Transport Modulators; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vasoconstrictor Agents; Calcium Channel Agonists; Dexamethasone; Calcitriol
• Other Study ID Numbers: RP 02-12; P30CA016056 (U.S. NIH Grant/Contract); RPCI-RP-0212