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
18 Years
N/A
Both
Colorectal Cancer
Trial Information
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
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).
Inclusion 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
Type of Study:
Interventional
Study Design:
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Supportive Care
Outcome Measure:
Identification of CYP24 single nucleotide polymorphisms (SNPs)
Outcome Time Frame:
Baseline, days 14, 30, 60, 90, 180, 270, 360
Safety Issue:
No
Principal Investigator
Marwan Fakih, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Roswell Park Cancer Institute
Authority:
United States: Food and Drug Administration
Study ID:
I 99207
NCT ID:
NCT00550563
Start Date:
August 2007
Completion Date:
July 2010
Related Keywords:
- Colorectal Cancer
- 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
- Colorectal Neoplasms
Name | Location |
|---|---|
| Roswell Park Cancer Institute | Buffalo, New York 14263 |
