Cholecalciferol and Calcium Carbonate in Treating Patients With Colon Cancer That Has Been Removed by Surgery

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
OBJECTIVES: Primary 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. Secondary 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.

Official Title
-----------------
A Pilot Study of Low and High Dose Vitamin Cholecalciferol (D3) With Pharmacokinetic and Pharmacodynamic Correlates in Patients With Resected Colon Cancer

Conditions
-----------------
Colorectal Cancer

Intervention / Treatment
-----------------
* Dietary Supplement: calcium carbonate
* Dietary Supplement: cholecalciferol
* Other: immunohistochemistry staining method
* Other: laboratory biomarker analysis
* Other: pharmacological study
* Procedure: biopsy


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: History of colon cancer Underwent resection and has been in clinical remission for ≥ 1 year No inflammatory bowel disease No familial adenomatous polyposis PATIENT CHARACTERISTICS: ECOG performance status 0-2 Life expectancy > 1 year No genitourinary stones within the past 5 years No severe comorbid conditions, such as uncompensated heart failure or active uncontrolled infection No history of hypercalcemia No active colostomy No contraindications to sigmoidoscopy or mucosal biopsies PRIOR CONCURRENT THERAPY: No prior rectal surgery or abdominoperineal resection At least 1 month since prior vitamin D or calcium supplementation Prior vitamin D supplemental intake ≤ 800 IU per day At least 1 year since prior chemotherapy No prior radiotherapy to the pelvis No concurrent active anticoagulation Patients who stop anticoagulation therapy at the time of mucosal biopsy are eligible No other concurrent supplemental calcium or vitamin D

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized


Arms and Interventions

| Intervention/Treatment |
| --- |
|Dietary Supplement: calcium carbonate|nan|
|Dietary Supplement: cholecalciferol|nan|
|Other: immunohistochemistry staining method|nan|
|Other: laboratory biomarker analysis|nan|
|Other: pharmacological study|nan|
|Procedure: biopsy|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in proliferative labeling index of normal rectal mucosa as measured by Ki67 IHC staining |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in serum levels of 25-OH-D3, 1,25-OH-D3, 24,25-OH-D3, calcium, and parathyroid hormone |  |  | 
| Safety of high-dose cholecalciferol supplementation as measured over 2 years |  | over 2 years | 
| 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 |  |  | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
recurrent colon cancer, stage I colon cancer, stage II colon cancer, stage III colon cancer