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

August 2, 2023 updated by: Roswell Park Cancer Institute

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

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)

Phase

Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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 Time Frame: 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

This is where you will find people and organizations involved with this study.

Sponsor

Roswell Park Cancer Institute

Collaborators

National Cancer Institute (NCI)

Investigators

Principal Investigator: Marwan Fakih, MD, Roswell Park Cancer Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

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