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

• Sponsor: Roswell Park Cancer Institute (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00084864
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 25
• Location: 1
• Arms: 4
• Duration (Months): 92
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Dietary Supplement: calcitriol; Drug: dexamethasone; Other: clinical observation	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pilot Trial of Calcitriol in Localized Prostate Cancer: Investigation of Biologic Effects and Potential Intermediate Endpoints
• Study Start Date: Sep 1, 2002
• Actual Primary Completion Date: Feb 1, 2010
• Actual Study Completion Date: May 1, 2010

Arms and Interventions

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.	Dietary Supplement: calcitriol; Given orally; Drug: dexamethasone; 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

Outcome Measures

Primary Outcome Measures

1. 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

1. 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]

2. 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.

3. Determine the Acute Effects of This Regimen on Serum PSA in These Patients. [Up to 30 days of the last administration of study procedure]

4. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Roswell Park Cancer Institute	Buffalo	New York	United States	14263-0001

Sponsors and Collaborators

• Roswell Park Cancer Institute
• National Cancer Institute (NCI)

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Roswell Park Cancer Institute
• ClinicalTrials.gov Identifier: NCT00084864
• Other Study ID Numbers: RP 02-12; P30CA016056; RPCI-RP-0212
• First Posted: Jun 11, 2004
• Last Update Posted: Jun 12, 2017
• Last Verified: May 1, 2017

• Keywords provided by Roswell Park Cancer Institute: adenocarcinoma of the prostate; stage II prostate cancer; stage III prostate cancer
• Additional relevant MeSH terms: Prostatic Neoplasms; Calcitriol; Dexamethasone

Study Results

Participant Flow

Arm/Group Title	Arm 1	Arm 2	Arm 3	Arm 4
Arm/Group Description	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	No study drugs before surgery. clinical observation: No intervention before surgery	Patients receive oral dexamethasone once daily on days 1-4. dexamethasone: Given orally	Patients receive oral calcitriol once daily on days 2-4. calcitriol: Given orally
Period Title: Overall Study
STARTED	10	7	4	4
COMPLETED	9	7	4	4
NOT COMPLETED	1	0	0	0

Baseline Characteristics

Arm/Group Title	Arm 1	Arm 2	Arm 3	Arm 4	Total
Arm/Group Description	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	No study drugs before surgery. clinical observation: No intervention before surgery	Patients receive oral dexamethasone once daily on days 1-4. dexamethasone: Given orally	Patients receive oral calcitriol once daily on days 2-4. calcitriol: Given orally	Total of all reporting groups
Overall Participants	10	7	4	4	25
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.0 (7.8)	56.3 (4.7)	54.5 (8.3)	50.2 (2.7)	55.7 (6.7)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%	0 0%
Male	10 100%	7 100%	4 100%	4 100%	25 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Study was activated in 9/2002 which was prior to Roswell Park Cancer Institute (RPCI) putting a system in place to centralize data entry and data management. Data entry of the outcomes was done by PI's staff and has since been lost. All attempts to retrieve the data have failed.

Arm/Group Title	Arm 1	Arm 2	Arm 3	Arm 4
Arm/Group Description	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	No study drugs before surgery. clinical observation: No intervention before surgery	Patients receive oral dexamethasone once daily on days 1-4. dexamethasone: Given orally	Patients receive oral calcitriol once daily on days 2-4. calcitriol: Given orally
Measure Participants	0	0	0	0

2. Secondary Outcome

Title	Effect of Preoperative High-dose Calcitriol and Dexamethasone on Extent of Prostatic Intraepithelial Neoplasia (PIN) at 1, 2, 3, and 12 Months Post Prostatectomy
Time Frame	Up to 30 days of the last administration of study procedure

Outcome Measure Data

Analysis Population Description

Study was activated in 9/2002 which was prior to Roswell Park Cancer Institute (RPCI) putting a system in place to centralize data entry and data management. Data entry of the outcomes was done by PI's staff and has since been lost. All attempts to retrieve the data have failed.

Arm/Group Title	Arm 1	Arm 2	Arm 3	Arm 4
Arm/Group Description	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	No study drugs before surgery. clinical observation: No intervention before surgery	Patients receive oral dexamethasone once daily on days 1-4. dexamethasone: Given orally	Patients receive oral calcitriol once daily on days 2-4. calcitriol: Given orally
Measure Participants	0	0	0	0

3. Secondary Outcome

Title	Determine the Effect of This Regimen on the Expression of Apoptosis Markers
Description	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.
Time Frame	Up to 30 days of the last administration of study procedure

Outcome Measure Data

Analysis Population Description

Study was activated in 9/2002 which was prior to Roswell Park Cancer Institute (RPCI) putting a system in place to centralize data entry and data management. Data entry of the outcomes was done by PI's staff and has since been lost. All attempts to retrieve the data have failed.

Arm/Group Title	Arm 1	Arm 2	Arm 3	Arm 4
Arm/Group Description	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	No study drugs before surgery. clinical observation: No intervention before surgery	Patients receive oral dexamethasone once daily on days 1-4. dexamethasone: Given orally	Patients receive oral calcitriol once daily on days 2-4. calcitriol: Given orally
Measure Participants	0	0	0	0

4. Secondary Outcome

Title	Determine the Acute Effects of This Regimen on Serum PSA in These Patients.
Time Frame	Up to 30 days of the last administration of study procedure

Outcome Measure Data

Analysis Population Description

Study was activated in 9/2002 which was prior to Roswell Park Cancer Institute (RPCI) putting a system in place to centralize data entry and data management. Data entry of the outcomes was done by PI's staff and has since been lost. All attempts to retrieve the data have failed.

Arm/Group Title	Arm 1	Arm 2	Arm 3	Arm 4
Arm/Group Description	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	No study drugs before surgery. clinical observation: No intervention before surgery	Patients receive oral dexamethasone once daily on days 1-4. dexamethasone: Given orally	Patients receive oral calcitriol once daily on days 2-4. calcitriol: Given orally
Measure Participants	0	0	0	0

5. Secondary Outcome

Title	Number of Participants With Adverse Events, Graded According to NCI CTCAE v2.0
Description	Number of Participants with Adverse Events, Graded According to NCI CTCAE v2.0
Time Frame	Up to 30 days of the last administration of study procedure

Outcome Measure Data

Analysis Population Description

All treated and eligible patients

Arm/Group Title	Arm 1	Arm 2	Arm 3	Arm 4
Arm/Group Description	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	No study drugs before surgery. clinical observation: No intervention before surgery	Patients receive oral dexamethasone once daily on days 1-4. dexamethasone: Given orally	Patients receive oral calcitriol once daily on days 2-4. calcitriol: Given orally
Measure Participants	10	7	4	4
Grade 1	1 10%	2 28.6%	2 50%	2 50%
Grade 2	3 30%	1 14.3%	1 25%	0 0%
Grade 3	1 10%	1 14.3%	0 0%	0 0%

Adverse Events

Arm/Group Title	Arm 1		Arm 2		Arm 3		Arm 4
Arm/Group Description	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		No study drugs before surgery. clinical observation: No intervention before surgery		Patients receive oral dexamethasone once daily on days 1-4. dexamethasone: Given orally		Patients receive oral calcitriol once daily on days 2-4. calcitriol: Given orally
All Cause Mortality
	Arm 1		Arm 2		Arm 3		Arm 4
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm 1		Arm 2		Arm 3		Arm 4
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		1/7 (14.3%)		0/4 (0%)		0/4 (0%)
Renal and urinary disorders
Urinary retention	0/10 (0%)	0	1/7 (14.3%)	1	0/4 (0%)	0	0/4 (0%)	0
Other (Not Including Serious) Adverse Events
	Arm 1		Arm 2		Arm 3		Arm 4
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/10 (50%)		4/7 (57.1%)		3/4 (75%)		2/4 (50%)
Ear and labyrinth disorders
Hypoacusis	0/10 (0%)	0	0/7 (0%)	0	0/4 (0%)	0	1/4 (25%)	1
Eye disorders
Vision blurred	0/10 (0%)	0	0/7 (0%)	0	1/4 (25%)	1	0/4 (0%)	0
Gastrointestinal disorders
Abdominal pain	0/10 (0%)	0	1/7 (14.3%)	1	0/4 (0%)	0	0/4 (0%)	0
Constipation	0/10 (0%)	0	1/7 (14.3%)	1	0/4 (0%)	0	0/4 (0%)	0
Nausea	0/10 (0%)	0	1/7 (14.3%)	1	0/4 (0%)	0	0/4 (0%)	0
General disorders
Chest pain	1/10 (10%)	1	1/7 (14.3%)	1	0/4 (0%)	0	0/4 (0%)	0
Pain	1/10 (10%)	1	0/7 (0%)	0	0/4 (0%)	0	0/4 (0%)	0
Metabolism and nutrition disorders
Hypercalcaemia	0/10 (0%)	0	0/7 (0%)	0	0/4 (0%)	0	1/4 (25%)	1
Hyperglycaemia	1/10 (10%)	1	0/7 (0%)	0	0/4 (0%)	0	0/4 (0%)	0
Hyperkalaemia	1/10 (10%)	1	0/7 (0%)	0	0/4 (0%)	0	0/4 (0%)	0
Hypernatraemia	1/10 (10%)	1	0/7 (0%)	0	1/4 (25%)	1	0/4 (0%)	0
Hyperphosphataemia	0/10 (0%)	0	0/7 (0%)	0	1/4 (25%)	1	0/4 (0%)	0
Hypoglycaemia	0/10 (0%)	0	0/7 (0%)	0	1/4 (25%)	1	0/4 (0%)	0
Hyponatraemia	0/10 (0%)	0	1/7 (14.3%)	1	0/4 (0%)	0	0/4 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	0/10 (0%)	0	0/7 (0%)	0	0/4 (0%)	0	1/4 (25%)	1
Musculoskeletal pain	0/10 (0%)	0	1/7 (14.3%)	1	0/4 (0%)	0	0/4 (0%)	0
Musculoskeletal stiffness	0/10 (0%)	0	0/7 (0%)	0	0/4 (0%)	0	1/4 (25%)	1
Nervous system disorders
Headache	1/10 (10%)	1	0/7 (0%)	0	0/4 (0%)	0	0/4 (0%)	0
Hypoaesthesia	0/10 (0%)	0	1/7 (14.3%)	1	1/4 (25%)	1	0/4 (0%)	0
Psychiatric disorders
Agitation	0/10 (0%)	0	0/7 (0%)	0	1/4 (25%)	1	0/4 (0%)	0
Renal and urinary disorders
Haematuria	0/10 (0%)	0	0/7 (0%)	0	0/4 (0%)	0	1/4 (25%)	1
Urethral pain	1/10 (10%)	1	0/7 (0%)	0	0/4 (0%)	0	0/4 (0%)	0
Urinary hesitation	0/10 (0%)	0	0/7 (0%)	0	0/4 (0%)	0	1/4 (25%)	1
Urinary incontinence	2/10 (20%)	2	0/7 (0%)	0	0/4 (0%)	0	0/4 (0%)	0
Urinary retention	1/10 (10%)	1	0/7 (0%)	0	0/4 (0%)	0	0/4 (0%)	0
Urine flow decreased	0/10 (0%)	0	1/7 (14.3%)	1	0/4 (0%)	0	0/4 (0%)	0
Reproductive system and breast disorders
Erectile dysfunction	1/10 (10%)	1	1/7 (14.3%)	1	0/4 (0%)	0	0/4 (0%)	0
Respiratory, thoracic and mediastinal disorders
Hiccups	1/10 (10%)	1	0/7 (0%)	0	0/4 (0%)	0	0/4 (0%)	0
Skin and subcutaneous tissue disorders
Ecchymosis	0/10 (0%)	0	0/7 (0%)	0	0/4 (0%)	0	1/4 (25%)	1
Rash papular	1/10 (10%)	1	0/7 (0%)	0	0/4 (0%)	0	0/4 (0%)	0
Vascular disorders
Flushing	1/10 (10%)	1	0/7 (0%)	0	0/4 (0%)	0	0/4 (0%)	0
Phlebitis	0/10 (0%)	0	0/7 (0%)	0	1/4 (25%)	1	0/4 (0%)	0

Limitations/Caveats

Study was activated prior to Roswell Park Cancer Institute (RPCI) putting a system in place to centralize data entry and data management. Data entry was done by PI's staff. PI left institute and left incomplete data.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.