Cholecalciferol(25-[OH]-Vitamin D) in Treating Patients With Colorectal Cancer

January 16, 2014 updated by: Case Comprehensive Cancer Center

Evaluation of the Effect of 25-OH-Vitamin D3 Therapy on 15-Prostaglandin Dehydrogenase Expression in Primary Tumor and Normal Colorectal Mucosa in Patients With Colorectal Cancer

This pilot clinical trial studies cholecalciferol in treating patients with colorectal cancer. The use of cholecalciferol may slow disease progression in patients with colorectal cancer.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. To compare the expression of 15-hydroxyprostaglandin dehydrogenase (PGDH) messenger ribonucleic acid (mRNA) and protein levels in tumor tissue at baseline and after treatment with 25-hydroxy (OH)-vitamin D3 (cholecalciferol).

II. To compare the expression of 15-PGDH mRNA and protein levels in normal colorectal mucosa at baseline and following treatment with 25-OH-vitamin D3.

SECONDARY OBJECTIVES:

I. To compare the expression of cyclooxygenase (COX)-1 and COX-2 mRNA in tumor tissues at baseline and after treatment with 25-OH-vitamin D3.

II. To compare levels of prostaglandin E2 (PGE2) in tumor tissue at baseline and after treatment with 25-OH-vitamin D3.

III. To compare the expression of COX-1 and COX-2 mRNA in normal colorectal mucosa at baseline and after treatment with 25-OH-vitamin D3.

IV. To compare levels of PGE2 in normal colorectal mucosa at baseline and after treatment with 25-OH-vitamin D3.

V. To evaluate the tolerability of a single 100,000 international unit (IU) dose of 25-OH-vitamin D3.

OUTLINE:

Patients receive cholecalciferol orally (PO) 7 days prior to scheduled surgery or endorectal ultrasound. Patients are only followed through surgery or endorectal ultrasound. In case of a vitamin-D-related toxicity, the patient will be followed for resolution of the toxicity, up to 6 months.

Study Type

Interventional

Phase

  • Early Phase 1

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

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients with a suspected diagnosis of adenocarcinoma of the rectum or sigmoid colon (e.g. based on appearance of mass or histology) referred to colorectal surgery who are expected to undergo routine proctosigmoidoscopy or flexible sigmoidoscopy in the surgeon's office as well as resection and/or endorectal ultrasound (EUS) as part of their routine care
  • The tumor must be accessible for biopsy and suitable for multiple biopsies
  • Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
  • Able to understand and willing to sign written informed consent document

Exclusion Criteria:

  • Prior anti-cancer therapy for this cancer such as chemotherapy, biologic therapy, immune therapy or radiation therapy
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Unable to swallow capsules
  • Underlying condition that will interfere with absorption of orally ingested vitamin D, e.g., untreated fat malabsorption
  • History of allergic reaction to cholecalciferol or other vitamin D preparations
  • EXCLUSION CRITERIA FOR DOSING VITAMIN D:
  • Elevated ionized calcium
  • Primary hyperparathyroidism
  • Renal failure with estimated glomerular filtration rate < 20 mL/min/1.73m^2 as calculated using the Modification of Diet in Renal Disease (MDRD) study equation for the isotope dilution mass spectrometry (IDMS) - traceable creatinine methods reported by University Hospital Case Medical Center (UHCMC) laboratory (due to less active formation of 1,25 hydroxyvitamin D due to less hydroxylase)
  • Serum 25-OH-vitamin D > 40 ng/ml

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (chemoprevention)
Patients receive cholecalciferol orally (PO) 7 days prior to scheduled surgery or endorectal ultrasound. Patients with sigmoid colon cancer or clinical stage I rectal cancer would proceed with surgical resection without preceding chemoradiation and will have a portion of normal colorectal mucosa and tumor tissue obtained for research purposes.
Other: laboratory biomarker analysis
Correlative studies
Procedure: biopsy
Correlative studies
Other Names:
  • biopsies
Other: enzyme-linked immunosorbent assay
Correlative studies
Other Names:
  • ELISA
Genetic: reverse transcriptase-polymerase chain reaction
Correlative studies
Other Names:
  • RT-PCR
Dietary supplement: cholecalciferol
Given PO
Other Names:
  • Vitamin D3
  • Calciol
Genetic: protein expression analysis
Correlative studies

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Comparison of the expression of 15-PGDH mRNA and protein levels in tumor tissue
Time Frame: 7-14 days after treatment
An increase in 15-PGDH expression will be defined as at least a 100% increase in mRNA by real-time reverse transcriptase (RT)-polymerase chain reaction (PCR) compared to baseline. Expression of 15-PGDH protein via ELISA in normal and tumor tissue at baseline and following treatment with vitamin D, as well as the absolute and fold changes will be summarized with descriptive statistics (e.g., mean, median, standard deviation, and interquartile range) and using box plots. In addition, 95% confidence intervals for the mean absolute and fold-changes in 15-PGDH levels will be calculated.
7-14 days after treatment
Comparison of the expression of 15-PGDH mRNA and protein levels in normal colorectal mucosa
Time Frame: 7-14 days after treatment
An increase in 15-PGDH expression will be defined as at least a 100% increase in mRNA by real-time reverse transcriptase (RT)-polymerase chain reaction (PCR) compared to baseline. Expression of 15-PGDH protein via ELISA in normal and tumor tissue at baseline and following treatment with vitamin D, as well as the absolute and fold changes will be summarized with descriptive statistics (e.g., mean, median, standard deviation, and interquartile range) and using box plots. In addition, 95% confidence intervals for the mean absolute and fold-changes in 15-PGDH levels will be calculated.
7-14 days after treatment

Secondary Outcome Measures

Outcome Measure
Time Frame
Comparison of the expression of COX-1 and COX-2 mRNA in tumor tissues
Time Frame: 7-14 days after treatment
7-14 days after treatment
Comparison of levels of PGE2 in tumor tissue
Time Frame: 7-14 days after treatment
7-14 days after treatment
Comparison of the expression of COX-1 and COX-2 mRNA in normal colorectal mucosa
Time Frame: 7-14 days after treatment
7-14 days after treatment
Comparison of levels of PGE2 in normal colorectal mucosa
Time Frame: 7-14 days after treatment
7-14 days after treatment
Number of patients with grade 3 related toxicities of a single 100,000 IU dose of 25-OH-vitamin D3
Time Frame: 18-25 days after treatment
18-25 days after treatment

Collaborators and Investigators

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

Sponsor

Case Comprehensive Cancer Center

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Matthew Kalady, MD, Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

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

April 1, 2012

Primary Completion (Actual)

January 1, 2014

Study Completion (Actual)

January 1, 2014

Study Registration Dates

First Submitted

July 25, 2011

First Submitted That Met QC Criteria

July 25, 2011

First Posted (Estimate)

July 27, 2011

Study Record Updates

Last Update Posted (Estimate)

January 17, 2014

Last Update Submitted That Met QC Criteria

January 16, 2014

Last Verified

January 1, 2014

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CASE2210
  • NCI-2011-01280 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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