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

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

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.

Study Overview

• Status: Terminated
• Conditions: Colorectal Cancer
• Intervention / Treatment: Other: pharmacological study; Other: laboratory biomarker analysis; Procedure: biopsy; Other: immunohistochemistry staining method; Dietary supplement: cholecalciferol; Dietary supplement: calcium carbonate

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.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14263-0001
      • Roswell Park Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Roswell Park Cancer Institute
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Marwan Fakih, MD, Roswell Park Cancer Institute

Study record dates

Study Major Dates

• Study Start: September 1, 2006
• Primary Completion (Actual): July 1, 2008
• Study Completion (Actual): September 1, 2009

Study Registration Dates

• First Submitted: May 3, 2007
• First Submitted That Met QC Criteria: May 3, 2007
• First Posted (Estimated): May 7, 2007

Study Record Updates

• Last Update Posted (Actual): August 4, 2023
• Last Update Submitted That Met QC Criteria: August 2, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: recurrent colon cancer; stage III colon cancer; stage II colon cancer; stage I colon cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Colorectal Neoplasms; Colonic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Antacids; Vitamin D; Cholecalciferol; Calcium; Calcium Carbonate
• Other Study ID Numbers: I 78706; RPCI-I-78706