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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


N/A
18 Years
N/A
Not Enrolling
Both
Colorectal Cancer

Thank you

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