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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Roswell Park Cancer Institute
ClinicalTrials.gov Identifier:
NCT00550563
First received: October 25, 2007
Last updated: July 12, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention
Colorectal Cancer
Dietary Supplement: cholecalciferol
Genetic: polymerase chain reaction
Genetic: polymorphism analysis
Genetic: protein expression analysis
Genetic: reverse transcriptase-polymerase chain reaction
Genetic: western blotting
Other: high performance liquid chromatography
Other: laboratory biomarker analysis
Other: pharmacological study
Procedure: adjuvant therapy
Procedure: immunoscintigraphy

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Supportive Care
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Roswell Park Cancer Institute:

Primary Outcome Measures:
  • Identification of CYP24 single nucleotide polymorphisms (SNPs) [ Time Frame: Baseline, days 14, 30, 60, 90, 180, 270, 360 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • CYP24 splicing, protein expression, and enzyme activity at baseline and during cholecalciferol treatment [ Time Frame: Baseline, days 14, 30, 60, 90, 180, 270, 360 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 50
Study Start Date: August 2007
Study Completion Date: July 2010
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00550563

Locations
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263-0001
Sponsors and Collaborators
Roswell Park Cancer Institute
Investigators
Principal Investigator: Marwan Fakih, MD Roswell Park Cancer Institute
  More Information

Additional Information:
No publications provided

Responsible Party: Roswell Park Cancer Institute
ClinicalTrials.gov Identifier: NCT00550563     History of Changes
Other Study ID Numbers: I 99207, RPCI-I-99207
Study First Received: October 25, 2007
Last Updated: July 12, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Roswell Park Cancer Institute:
recurrent colon cancer
stage I colon cancer
stage II colon cancer
stage III colon cancer
stage IV colon cancer
recurrent rectal cancer
stage I rectal cancer
stage II rectal cancer
stage III rectal cancer
stage IV rectal cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Cholecalciferol
Vitamin D
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on April 21, 2014