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

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• Status: Withdrawn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: Mucinous Adenocarcinoma of the Rectum; Signet Ring Adenocarcinoma of the Rectum; Mucinous Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Colon; Stage I Colon Cancer; Stage I Rectal Cancer
• Intervention / Treatment: Other: laboratory biomarker analysis; Procedure: biopsy; Other: enzyme-linked immunosorbent assay; Genetic: reverse transcriptase-polymerase chain reaction; Dietary supplement: cholecalciferol; Genetic: protein expression analysis

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

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

How is the study designed?

Design Details

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

Number of Arms

1

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	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	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	7-14 days after treatment
Comparison of levels of PGE2 in tumor tissue	7-14 days after treatment
Comparison of the expression of COX-1 and COX-2 mRNA in normal colorectal mucosa	7-14 days after treatment
Comparison of levels of PGE2 in normal colorectal mucosa	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	18-25 days after treatment

Collaborators and Investigators

• 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

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: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Neoplasms, Cystic, Mucinous, and Serous; Adenocarcinoma; Rectal Neoplasms; Cystadenocarcinoma; Adenocarcinoma, Mucinous; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: CASE2210; NCI-2011-01280 (Registry Identifier: CTRP (Clinical Trial Reporting Program))