DNA Changes That Affect Vitamin D Metabolism in Patients With Colorectal Cancer Receiving Vitamin D Supplements
This study has been completed.
Sponsor:
Roswell Park Cancer Institute
Information provided by (Responsible Party):
Roswell Park Cancer Institute
ClinicalTrials.gov Identifier:
NCT00550563
First received: October 25, 2007
Last updated: September 23, 2011
Last verified: September 2011
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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: | June 2008 (Final data collection date for primary outcome measure) |
Intervention Details:
Detailed Description:
-
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
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: | September 23, 2011 |
| 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 May 16, 2013