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

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00084864

Enrollment

Registered

2004-06-11

Start date

2002-09-30

Completion date

2010-05-31

Last updated

2017-06-12

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Prostate Cancer

Keywords

adenocarcinoma of the prostate, stage II prostate cancer, stage III prostate cancer

Brief summary

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.

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.

Interventions

DIETARY_SUPPLEMENTcalcitriol

Given orally

DRUGdexamethasone

Given orally

OTHERclinical observation

No intervention before surgery

Study design

Allocation

RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

MALE

Age

18 Years to 120 Years

Healthy volunteers

Inclusion criteria

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

Design outcomes

Primary

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

Measure	Time frame	Description
Determine the Acute Effects of This Regimen on Serum PSA in These Patients.	Up to 30 days of the last administration of study procedure	—
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	Up to 30 days of the last administration of study procedure	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.
Number of Participants With Adverse Events, Graded According to NCI CTCAE v2.0	Up to 30 days of the last administration of study procedure	Number of Participants with Adverse Events, Graded According to NCI CTCAE v2.0

Countries

United States

Participant flow

Participants by arm

Arm	Count
Arm 1 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. calcitriol: Given orally dexamethasone: Given orally	10
Arm 2 No study drugs before surgery. clinical observation: No intervention before surgery	7
Arm 3 Patients receive oral dexamethasone once daily on days 1-4. dexamethasone: Given orally	4
Arm 4 Patients receive oral calcitriol once daily on days 2-4. calcitriol: Given orally	4
Total	25

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003
Overall Study	Adverse Event	1	0	0	0

Baseline characteristics

Characteristic	Arm 1	Arm 2	Arm 3	Arm 4	Total
Age, Continuous	58.0 years STANDARD_DEVIATION 7.8	56.3 years STANDARD_DEVIATION 4.7	54.5 years STANDARD_DEVIATION 8.3	50.2 years STANDARD_DEVIATION 2.7	55.7 years STANDARD_DEVIATION 6.7
Sex: Female, Male Female	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Sex: Female, Male Male	10 Participants	7 Participants	4 Participants	4 Participants	25 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —
other Total, other adverse events	5 / 10	4 / 7	3 / 4	2 / 4
serious Total, serious adverse events	0 / 10	1 / 7	0 / 4	0 / 4