Cholecalciferol Supplement in Treating Patients With Localized Prostate Cancer Undergoing Observation

• Sponsor: Roswell Park Cancer Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT00887432
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 132
• Location: 1
• Arms: 2
• Actual Duration (Months): 134
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

This randomized clinical trial studies how well cholecalciferol supplement works in treating patients with localized prostate cancer undergoing observation. Cholecalciferol may help prostate cancer cells become more like normal cells, and to grow and spread more slowly.

Condition or Disease	Intervention/Treatment	Phase
Prostate Adenocarcinoma	Dietary Supplement: Cholecalciferol; Other: Laboratory Biomarker Analysis; Other: Patient Observation; Drug: Placebo Administration; Other: Quality-of-Life Assessment; Other: Questionnaire Administration	N/A

Detailed Description

PRIMARY OBJECTIVES:

1. To determine the prostate-specific antigen (PSA) response with oral high dose vitamin D3 supplementation (cholecalciferol) in patients with localized, histologically proven adenocarcinoma of the prostate who have not received any treatment for prostate cancer ever and have chosen expectant management.

SECONDARY OBJECTIVES:

1. To examine the pattern of response of PSA dynamics as well as the absolute change in PSA following vitamin D3 supplementation.

2. Assess the toxicity of vitamin D3 supplementation in men with prostate cancer.

TERTIARY OBJECTIVES:

1. Track occurrence of infections, deep venous thrombosis, vascular events and falls in the study population.

2. To evaluate relationship between cytochrome P450 family 24 (CYP24), 27B1, single-nucleotide polymorphism (SNPs) and serum 25(hydroxy [OH]) vitamin D response to oral D3 supplementation.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive cholecalciferol orally (PO) once daily (QD) for 9 months in the absence of disease progression or unacceptable toxicity. After a wash-out period of 3 months, patients cross-over to Arm II.

ARM II: Patients receive placebo PO QD for 9 months in the absence of disease progression or unacceptable toxicity. After a wash-out period of 3 months, patients cross-over to Arm I.

After completion of study treatment, patients are followed up for 30 days.

Study Design

• Study Type: Interventional
• Actual Enrollment: 132 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Randomized Placebo-Controlled, Double-Blind Study of Cholecalciferol Replacement in Patients on Expectant Management for Localized Prostate Cancer
• Actual Study Start Date: Apr 8, 2009
• Actual Primary Completion Date: Jun 8, 2020
• Actual Study Completion Date: Jun 8, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I (cholecalciferol and placebo) Patients receive cholecalciferol PO QD for 9 months in the absence of disease progression or unacceptable toxicity. After a wash-out period of 3 months, patients cross-over to Arm II.	Dietary Supplement: Cholecalciferol; Given PO; Other Names: 9,10-Secocholesta-5,7,10(19)-trien-3-ol Calciol Delsterol Vitamin D3 ; Other: Laboratory Biomarker Analysis; Correlative studies; Other: Patient Observation; Other Names: Active Surveillance deferred therapy expectant management Observation Watchful Waiting ; Drug: Placebo Administration; Given PO; Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment ; Other: Questionnaire Administration; Ancillary studies
Experimental: Arm II (placebo and cholecalciferol) Patients receive placebo PO QD for 9 months in the absence of disease progression or unacceptable toxicity. After a wash-out period of 3 months, patients cross-over to Arm I.	Dietary Supplement: Cholecalciferol; Given PO; Other Names: 9,10-Secocholesta-5,7,10(19)-trien-3-ol Calciol Delsterol Vitamin D3 ; Other: Laboratory Biomarker Analysis; Correlative studies; Other: Patient Observation; Other Names: Active Surveillance deferred therapy expectant management Observation Watchful Waiting ; Drug: Placebo Administration; Given PO; Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment ; Other: Questionnaire Administration; Ancillary studies

Outcome Measures

Primary Outcome Measures

1. PSA Response [9 month period: pre-Vitamin D/pre-placebo to 9 months after start of vitamin D/ placebo, up to 30 days after completion of study treatment]

   Difference in the mean change in PSA on vitamin D (9 month period: pre-Vitamin D to 9 months after start of vitamin D) versus on placebo (9 month period: pre-Placebo to 9 months after starting placebo). Compared using a paired t-test.

Secondary Outcome Measures

1. Slope of PSA Concentration Over Time [9 month period: pre-Vitamin D/pre-placebo to 9 months after start of vitamin D/ placebo, up to 30 days after completion of study treatment -Up to 30 days after completion of study treatment]

   The PSA levels were modeled as a function of treatment, time, their interaction, sequence, and a random subject effect using a linear mixed model. From this model, the subject specific PSA slope was obtained for each subject under each condition (vitamin D versus placebo). The PSA slopes were then compared between treatment conditions using linear mixed model to account for treatment arm and repeated measures.

2. Toxicity as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 [Up to 30 days after completion of study treatment (up to 22 months from start of study).]

   Summarizing the maximum observed treatment related adverse event. Summarize by arm and grade using frequencies and relative frequencies..

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Any patient with clinically localized, histologically proven adenocarcinoma of prostate who has not received any treatment for prostate cancer ever and has chosen active surveillance; treatment for prostate cancer is defined as prostatectomy, androgen deprivation, brachytherapy or a full course of external beam irradiation

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Willingness to comply with study guidelines

• Willingness and ability to consent

• 25(OH) D3 level less than 40 ng/ml within 3 months of initiation of study; most recent 25 hydroxy D level within last 3 month would be used

Exclusion Criteria:

• History of malabsorption syndrome e.g., pancreatic insufficiency, celiac disease, tropical sprue

• Creatinine > 2.0 mg/dL

• Corrected serum calcium level of > 10.5 mg/dL (serum corrected calcium = serum calcium

• 0.8[4-serum albumin])

• Most recent PSA value more than 18 months ago

• Prior or current therapy for prostate cancer

• Documented history of nephrolithiasis within the past 5 years

• Patients receiving finasteride (Proscar) or dutasteride (Avodart) or men who have received either agent within 90 days of entry are ineligible

• Patients cannot take any additional vitamin D supplementation during study treatment; patients taking > 2000 IU per day prior to treatment will be ineligible

Contacts and Locations

Locations

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

Sponsors and Collaborators

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

Investigators

• Principal Investigator: James Mohler, Roswell Park Cancer Institute

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 26, 2018

More Information

Publications

None provided.

• Responsible Party: Roswell Park Cancer Institute
• ClinicalTrials.gov Identifier: NCT00887432
• Other Study ID Numbers: I 128308; NCI-2009-01530; I 128308; P30CA016056
• First Posted: Apr 24, 2009
• Last Update Posted: Oct 26, 2021
• Last Verified: Oct 1, 2021

• Additional relevant MeSH terms: Adenocarcinoma; Vitamin D; Cholecalciferol

Study Results

Participant Flow

Arm/Group Title	Cholecalciferol to Placebo	Placebo to Cholecalciferol
Arm/Group Description	Patients receive cholecalciferol PO QD for 9 months in the absence of disease progression or unacceptable toxicity. After a wash-out period of 3 months, patients cross-over to placebo PO QD for 9 months. Cholecalciferol: Given PO Laboratory Biomarker Analysis: Correlative studies Patient Observation Placebo Administration: Given PO Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies	Patients receive placebo PO QD for 9 months in the absence of disease progression or unacceptable toxicity. After a wash-out period of 3 months, patients cross-over to Cholecalciferol PO QD for 9 months. Cholecalciferol: Given PO Laboratory Biomarker Analysis: Correlative studies Patient Observation Placebo Administration: Given PO Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies
Period Title: Overall Study
STARTED	58	74
COMPLETED	43	60
NOT COMPLETED	15	14

Baseline Characteristics

Arm/Group Title	Arm I (Cholecalciferol and Placebo)	Arm II (Placebo and Cholecalciferol)	Total
Arm/Group Description	Patients receive cholecalciferol PO QD for 9 months in the absence of disease progression or unacceptable toxicity. After a wash-out period of 3 months, patients cross-over to placebo PO QD for 9 months. Cholecalciferol: Given PO Laboratory Biomarker Analysis: Correlative studies Patient Observation Placebo Administration: Given PO Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies	Patients receive placebo PO QD for 9 months in the absence of disease progression or unacceptable toxicity. After a wash-out period of 3 months, patients cross-over to cholecalciferol PO QD for 9 months. Cholecalciferol: Given PO Laboratory Biomarker Analysis: Correlative studies Patient Observation Placebo Administration: Given PO Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies	Total of all reporting groups
Overall Participants	58	74	132
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	33 56.9%	35 47.3%	68 51.5%
>=65 years	25 43.1%	39 52.7%	64 48.5%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.5 (7.0)	64.9 (6.5)	64.3 (6.8)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	58 100%	74 100%	132 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 1.7%	0 0%	1 0.8%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	5 8.6%	5 6.8%	10 7.6%
White	50 86.2%	69 93.2%	119 90.2%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	2 3.4%	0 0%	2 1.5%
Region of Enrollment (Count of Participants)
United States	58 100%	74 100%	132 100%
Serum 25(OH)D3 (ng/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ng/mL]	25.1 (10.7)	30.4 (9.0)	27.9 (10.0)
Prostate Specific Antigen (PSA) (ng/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ng/mL]	5.2 (2.9)	4.8 (2.6)	5.0 (2.7)

Outcome Measures

1. Primary Outcome

Title	PSA Response
Description	Difference in the mean change in PSA on vitamin D (9 month period: pre-Vitamin D to 9 months after start of vitamin D) versus on placebo (9 month period: pre-Placebo to 9 months after starting placebo). Compared using a paired t-test.
Time Frame	9 month period: pre-Vitamin D/pre-placebo to 9 months after start of vitamin D/ placebo, up to 30 days after completion of study treatment

Outcome Measure Data

Analysis Population Description

Patients who completed both periods.

Arm/Group Title	Cholecalciferol	Placebo
Arm/Group Description	Patients receive cholecalciferol PO QD for 9 months in the absence of disease progression or unacceptable toxicity. Cholecalciferol: Given PO Laboratory Biomarker Analysis: Correlative studies Patient Observation Placebo Administration: Given PO Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies	Patients receive placebo PO QD for 9 months in the absence of disease progression or unacceptable toxicity. Cholecalciferol: Given PO Laboratory Biomarker Analysis: Correlative studies Patient Observation Placebo Administration: Given PO Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies
Measure Participants	87	87
Mean (Standard Deviation) [ng/mL]	0.55 (2.13)	0.31 (1.86)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cholecalciferol, Placebo
	Comments	Evaluated the change in PSA under the vitamin D and placebo conditions using the combined data (n=87).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.431
	Comments	Significance level of 0.05.
	Method	t-test, 2 sided
	Comments	Paired t-test, df=86
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.24
	Confidence Interval	(2-Sided) 95%; -0.36 to 0.84
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Slope of PSA Concentration Over Time
Description	The PSA levels were modeled as a function of treatment, time, their interaction, sequence, and a random subject effect using a linear mixed model. From this model, the subject specific PSA slope was obtained for each subject under each condition (vitamin D versus placebo). The PSA slopes were then compared between treatment conditions using linear mixed model to account for treatment arm and repeated measures.
Time Frame	9 month period: pre-Vitamin D/pre-placebo to 9 months after start of vitamin D/ placebo, up to 30 days after completion of study treatment -Up to 30 days after completion of study treatment

Outcome Measure Data

Analysis Population Description

Including evaluable patients, those patients with data available under both the vitamin D and placebo conditions.

Arm/Group Title	Cholecalciferol	Placebo
Arm/Group Description	Patients receive cholecalciferol PO QD for 9 months in the absence of disease progression or unacceptable toxicity. Cholecalciferol: Given PO Laboratory Biomarker Analysis: Correlative studies Patient Observation Placebo Administration: Given PO Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies	Patients receive placebo PO QD for 9 months in the absence of disease progression or unacceptable toxicity. Cholecalciferol: Given PO Laboratory Biomarker Analysis: Correlative studies Patient Observation Placebo Administration: Given PO Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies
Measure Participants	119	120
Least Squares Mean (Standard Error) [(ng/mL) / day]	0.000434 (0.000089)	0.000245 (0.000090)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cholecalciferol, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments	Comparing the mean PSA slopes between conditions (on vitamin D versus on placebo).
Statistical Test of Hypothesis	p-Value	0.112
	Comments	Significance level of 0.05.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.00019
	Confidence Interval	(2-Sided) 95%; -0.00042 to 0.000045
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Toxicity as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0
Description	Summarizing the maximum observed treatment related adverse event. Summarize by arm and grade using frequencies and relative frequencies..
Time Frame	Up to 30 days after completion of study treatment (up to 22 months from start of study).

Outcome Measure Data

Analysis Population Description

All patients receiving any treatment

Arm/Group Title	Cholecalciferol	Placebo
Arm/Group Description	Patients receive cholecalciferol PO QD for 9 months in the absence of disease progression or unacceptable toxicity. Cholecalciferol: Given PO Laboratory Biomarker Analysis: Correlative studies Patient Observation Placebo Administration: Given PO Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies	Patients receive placebo PO QD for 9 months in the absence of disease progression or unacceptable toxicity. Cholecalciferol: Given PO Laboratory Biomarker Analysis: Correlative studies Patient Observation Placebo Administration: Given PO Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies
Measure Participants	119	120
No AE	117 201.7%	118 159.5%
Grade 1	1 1.7%	2 2.7%
Grade 2	0 0%	0 0%
Grade 3	1 1.7%	0 0%
Grade 4	0 0%	0 0%
Grade 5	0 0%	0 0%

Adverse Events

Time Frame	Within 30 days of treatment completion (up to 22 months from start of study).
Arm/Group Title	Cholecalciferol		Placebo
Arm/Group Description	Patients receive cholecalciferol PO QD for 9 months in the absence of disease progression or unacceptable toxicity. Cholecalciferol: Given PO Laboratory Biomarker Analysis: Correlative studies Patient Observation Placebo Administration: Given PO Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies		Patients receive placebo PO QD for 9 months in the absence of disease progression or unacceptable toxicity. Cholecalciferol: Given PO Laboratory Biomarker Analysis: Correlative studies Patient Observation Placebo Administration: Given PO Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies
All Cause Mortality
	Cholecalciferol		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/119 (0%)		0/120 (0%)
Serious Adverse Events
	Cholecalciferol		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/119 (0%)		0/120 (0%)
Other (Not Including Serious) Adverse Events
	Cholecalciferol		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/119 (1.7%)		2/120 (1.7%)
Metabolism and nutrition disorders
Hypophosphataemia	1/119 (0.8%)	1	0/120 (0%)	0
Musculoskeletal and connective tissue disorders
Myalgia	0/119 (0%)	0	2/120 (1.7%)	2
Renal and urinary disorders
Nephrolithiasis	1/119 (0.8%)	1	0/120 (0%)	0

Limitations/Caveats

[Not Specified]

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.