Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs No phase specified Biomarker/Laboratory analysis, Treatment Active 18 and over NCI RPCI-I-78706 NCT00470353

Objectives

Primary

1. 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

1. 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.
2. Determine the safety of high-dose cholecalciferol in these patients over 2 years.
3. 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.

Entry 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

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

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

Expected Enrollment

A total of 20 patients will be accrued for this study.

Outcomes

Change in proliferative labeling index of normal rectal mucosa as measured by Ki67 IHC staining

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
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

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.

Trial Contact Information

Trial Lead Organizations

Roswell Park Cancer Institute

Marwan Fakih, MD, Principal investigator		Ph: 716-845-3362; 800-685-6825 Email: marwan.fakih@roswellpark.org

U.S.A.
New York
	Buffalo
	Roswell Park Cancer Institute
		Marwan Fakih, MD	Ph:  716-845-8189
			Email: marwan.fakih@roswellpark.org

Registry Information
Official Title		A Pilot Study of Low and High Dose Vitamin Cholecalciferol (D3) with Pharmacokinetic and Pharmacodynamic Correlates in Patients with Resected Colon Cancer
Trial Start Date		2006-09-26
Trial Completion Date		2009-09-03 (estimated)
Registered in ClinicalTrials.gov		NCT00470353
Date Submitted to PDQ		2007-04-06
Information Last Verified		2008-04-20
NCI Grant/Contract Number		CA16056