Cholecalciferol and Calcium Carbonate in Treating Patients With Colon Cancer That Has Been Removed by Surgery
RATIONALE: The use of cholecalciferol and calcium carbonate may keep colon cancer from coming back in patients with colon cancer that has been removed by surgery.
PURPOSE: This randomized clinical trial is studying two different doses of cholecalciferol to compare how well they work when given together with calcium carbonate in treating patients with colon cancer that has been removed by surgery.
Dietary Supplement: calcium carbonate
Dietary Supplement: cholecalciferol
Other: immunohistochemistry staining method
Other: laboratory biomarker analysis
Other: pharmacological study
|Study Design:||Allocation: Randomized
Primary Purpose: Treatment
|Official Title:||A Pilot Study of Low and High Dose Vitamin Cholecalciferol (D3) With Pharmacokinetic and Pharmacodynamic Correlates in Patients With Resected Colon Cancer|
- Change in proliferative labeling index of normal rectal mucosa as measured by Ki67 IHC staining [ Designated as safety issue: No ]
- Changes in serum levels of 25-OH-D3, 1,25-OH-D3, 24,25-OH-D3, calcium, and parathyroid hormone [ Designated as safety issue: No ]
- Safety of high-dose cholecalciferol supplementation as measured over 2 years [ Time Frame: over 2 years ] [ Designated as safety issue: Yes ]
- Effects of cholecalciferol on biological markers of proliferation (i.e., cyclin D1, protein kinase C, vitamin D receptor, p21, and p27) as measured by IHC at baseline and after 6 months of study treatment [ Designated as safety issue: No ]
|Study Start Date:||September 2006|
|Study Completion Date:||September 2009|
|Primary Completion Date:||July 2008 (Final data collection date for primary outcome measure)|
- Compare the antiproliferative effects of 2 different doses of cholecalciferol (i.e., vitamin D3) in combination with calcium carbonate on the proliferative labeling index in patients with resected colon cancer.
- Compare the effects of these doses on serum levels of 25-OH-D3, 1,25-OH-D3, 24,25-OH-D3, calcium, and parathyroid hormone in these patients.
- Determine the safety of high-dose cholecalciferol in these patients over 2 years.
- Compare the effects of these doses on several biological markers (i.e., cyclin D1, protein kinase C, vitamin D receptor, p21, and p27) in the rectal mucosa of these patients.
OUTLINE: This is a randomized, pilot study. Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive oral low-dose cholecalciferol once daily and oral calcium carbonate twice daily.
- Arm II: Patients receive oral high-dose cholecalciferol once daily and calcium carbonate as in arm I.
Treatment in both arms continues for up to 2 years in the absence of disease progression or unacceptable toxicity. All patients undergo sigmoidoscopy or colonoscopy with 4 quadrant mucosal biopsies at baseline and after 6 months of study treatment. After their 6-month mucosal biopsy, patients in arm I switch to high-dose cholecalciferol as in arm II.
Patients undergo blood, urine, and tissue collection periodically during study for pharmacokinetic, pharmacodynamic, and/or histopathological analysis. Serum is collected monthly for 3 months and then once every 3 months to assess changes in serum levels of vitamin D and vitamin D metabolites (i.e., 1,25-OH-D3; 25-OH-D3; 24,25-OH-D3), as well as changes in calcium and parathyroid hormone, BUN, creatinine, electrolytes, and phosphorus levels. Urine is collected once every 3 months to assess changes in urine calcium and creatinine levels for hypercalciuria. Tissue biopsies of normal endorectal mucosa collected at baseline and after 6 months of study treatment are evaluated by IHC for proliferative index, vitamin D receptor staining, p21, p27, cyclin D1, and protein kinase C.
PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00470353
|United States, New York|
|Roswell Park Cancer Institute|
|Buffalo, New York, United States, 14263-0001|
|Principal Investigator:||Marwan Fakih, MD||Roswell Park Cancer Institute|