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)
132
1
2
134
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
  • 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)

    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:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    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).
    Adverse Event Reporting Description
    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.

    Results Point of Contact

    Name/Title Kris Attwood
    Organization Roswell Park Comprehensive Cancer Center
    Phone 716-845-1300
    Email Kris.Attwood@roswellpark.org
    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