Colorectal Cancer
Conditions
Keywords
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
Brief summary
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.
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).
Interventions
DIETARY_SUPPLEMENTcholecalciferol
Oral
GENETICpolymerase chain reaction
companion study
GENETICpolymorphism analysis
companion study
GENETICprotein expression analysis
companion study
GENETICreverse transcriptase-polymerase chain reaction
companion study
GENETICwestern blotting
companion study
OTHERhigh performance liquid chromatography
companion study
OTHERlaboratory biomarker analysis
companion study
OTHERpharmacological study
companion study
PROCEDUREadjuvant therapy
Additional therapy
PROCEDUREimmunoscintigraphy
additional testing
Sponsors
Roswell Park Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Identification of CYP24 single nucleotide polymorphisms (SNPs) | 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) | At baseline |
| Effect of CYP24 SNPs on serum vitamin D3 metabolites and PTH levels during cholecalciferol treatment | Baseline, days 14, 30, 60, 90, 180, 270, 360 |
| CYP24 splicing, protein expression, and enzyme activity at baseline and during cholecalciferol treatment | Baseline, days 14, 30, 60, 90, 180, 270, 360 |
| Relationship between serum cholecalciferol pharmacokinetic parameters and CYP24 SNPs, splicing variants, and enzyme activity | Baseline, days 14, 30, 60, 90, 180, 270, 360 |
Countries
United States
Outcome results
None listed