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

Early Phase 1

Withdrawn

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

• Registration Number: NCT01403103
• Lead Sponsor: Case Comprehensive Cancer Center

Brief Summary

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.

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 Timeline

• Study First Submitted: 2011-07-25
• Study First Submitted QC: 2011-07-25
• Study First Posted: 2011-07-27
• Study Start: 2012-04
• Status Verified: 2014-01
• Primary Completion: 2014-01
• Study Completion: 2014-01
• Last Update Submitted: 2014-01-16
• Last Update Posted: 2014-01-17

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (chemoprevention)	cholecalciferol	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.
Treatment (chemoprevention)	biopsy	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.
Treatment (chemoprevention)	protein expression analysis	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.
Treatment (chemoprevention)	enzyme-linked immunosorbent assay	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.
Treatment (chemoprevention)	laboratory biomarker analysis	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.
Treatment (chemoprevention)	reverse transcriptase-polymerase chain reaction	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.

Primary Outcome Measures

Name	Time	Method
Comparison of the expression of 15-PGDH mRNA and protein levels in tumor tissue	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.
Comparison of the expression of 15-PGDH mRNA and protein levels in normal colorectal mucosa	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.

Secondary Outcome Measures

Name	Time	Method
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
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 levels of PGE2 in normal colorectal mucosa	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