DNA Changes That Affect Vitamin D Metabolism in Patients With Colorectal Cancer Receiving Vitamin D Supplements

March 31, 2017 updated by: Roswell Park Cancer Institute

Identification of 24-Hydroxylase Polymorphisms and Splicing Variants That Modulate Vitamin D Oxidative Metabolism and Serum Pharmacokinetics in Patients With Colorectal Cancer on Cholecalciferol Therapy

RATIONALE: Studying samples of blood from patients with cancer in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer.

PURPOSE: This clinical trial is studying changes in DNA that affect vitamin D metabolism in patients with colorectal cancer receiving vitamin D supplements.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • To identify CYP24 single nucleotide polymorphisms (SNPs) using peripheral blood mononuclear cell genomic DNA from patients with colorectal cancer receiving cholecalciferol supplementation.
  • To evaluate the effects of these CYP24 SNPs on baseline serum vitamin D_3 metabolites (25-D_3, 24,25-D_3, and 1,25-D_3), and parathyroid hormone levels (PTH).
  • To evaluate the effects of these CYP24 SNPs on serum vitamin D_3 metabolites and PTH levels during cholecalciferol treatment.
  • To examine CYP24 splicing, protein expression, and enzyme activity at baseline and during cholecalciferol treatment.
  • To determine the relationship, if any, between serum cholecalciferol pharmacokinetic parameters and CYP24 SNPs, splicing variants, and enzyme activity.

OUTLINE: Patients receive oral cholecalciferol 2000 IU once daily for 1 year. Patients without response to vitamin D supplementation (serum 25-D_3 level < 32 ng/mL) by 6 months will have their cholecalciferol dose increased to 4000 IU once daily.

Blood is collected at baseline and on days 14, 30, 60, 90, 180, 270, and 360. Peripheral blood mononuclear cells for CYP24 genotyping, protein expression, enzyme activity, and splicing variants are analyzed by polymerase chain reaction (PCR), western blot, high performance liquid chromatography, and reverse transcriptase PCR, respectively. Serum is analyzed for vitamin D_3 metabolite levels (by radioimmunoassay), calcium (to monitor for hypercalcemia), and parathyroid hormone assays (to measure vitamin D effect).

Study Type

Interventional

Enrollment (Actual)

50

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Prior or current documented diagnosis of colorectal cancer

    • All stages
  • 25OH-D3 level < 50 ng/mL

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Life expectancy > 6 months
  • Serum creatinine < 2.0 mg/dL
  • Serum bilirubin < 2.0 mg/dL
  • No prior or current hypercalcemia (defined as albumin corrected serum calcium < 10.2 mg/dL)
  • No known contraindication for vitamin D supplementation
  • No genitourinary stones within the past 5 years
  • No severe comorbid conditions such as uncompensated heart failure or active infection

PRIOR CONCURRENT THERAPY:

  • No supplemental vitamin D beyond what is provided through the study

  • At least 2 months since prior vitamin D supplementation exceeding 800 International Units (IU)

    • Nondietary vitamin D supplements should not have exceeded 800 IU/day within the past 2 months

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Oral Cholecalciferol
Patients receive oral cholecalciferol 2000 IU once daily for 1 year
Dietary supplement: cholecalciferol
Oral
Genetic: polymerase chain reaction
companion study
Genetic: polymorphism analysis
companion study
Genetic: protein expression analysis
companion study
Genetic: reverse transcriptase-polymerase chain reaction
companion study
Genetic: western blotting
companion study
Other: high performance liquid chromatography
companion study
Other: laboratory biomarker analysis
companion study
Other: pharmacological study
companion study
Procedure: adjuvant therapy
Additional therapy
Procedure: immunoscintigraphy
additional testing

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Identification of CYP24 single nucleotide polymorphisms (SNPs)
Time Frame: Baseline, days 14, 30, 60, 90, 180, 270, 360
Baseline, days 14, 30, 60, 90, 180, 270, 360
Effect of CYP24 SNPs on baseline serum vitamin D3 metabolites (25-D3, 24,25-D3, and 1,25-D3), and parathyroid hormone levels (PTH)
Time Frame: At baseline
At baseline
Effect of CYP24 SNPs on serum vitamin D3 metabolites and PTH levels during cholecalciferol treatment
Time Frame: Baseline, days 14, 30, 60, 90, 180, 270, 360
Baseline, days 14, 30, 60, 90, 180, 270, 360
CYP24 splicing, protein expression, and enzyme activity at baseline and during cholecalciferol treatment
Time Frame: Baseline, days 14, 30, 60, 90, 180, 270, 360
Baseline, days 14, 30, 60, 90, 180, 270, 360
Relationship between serum cholecalciferol pharmacokinetic parameters and CYP24 SNPs, splicing variants, and enzyme activity
Time Frame: Baseline, days 14, 30, 60, 90, 180, 270, 360
Baseline, days 14, 30, 60, 90, 180, 270, 360

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Roswell Park Cancer Institute

Investigators

  • Principal Investigator: Marwan Fakih, MD, Roswell Park Cancer Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2007

Primary Completion (Actual)

April 1, 2009

Study Completion (Actual)

July 1, 2010

Study Registration Dates

First Submitted

October 25, 2007

First Submitted That Met QC Criteria

October 25, 2007

First Posted (Estimate)

October 30, 2007

Study Record Updates

Last Update Posted (Actual)

April 4, 2017

Last Update Submitted That Met QC Criteria

March 31, 2017

Last Verified

March 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • I 99207
  • RPCI-I-99207

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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