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

Mucinous Adenocarcinoma of the Rectum Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01403103
• Other study ID #: CASE2210
• Secondary ID: NCI-2011-01280
• Status: Withdrawn
• Phase: Phase 0
• First received: July 25, 2011
• Last updated: January 16, 2014
• Start date: April 2012
• Est. completion date: January 2014

Study information

• Verified date: January 2014
• Source: Case Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: January 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma, Mucinous
• Colorectal Neoplasms
• Cystadenocarcinoma
• Mucinous Adenocarcinoma of the Colon
• Mucinous Adenocarcinoma of the Rectum
• Rectal Neoplasms
• Signet Ring Adenocarcinoma of the Colon
• Signet Ring Adenocarcinoma of the Rectum
• Stage I Colon Cancer
• Stage I Rectal Cancer

Intervention

Dietary Supplement:
• cholecalciferol
Given PO

Procedure:
• biopsy
Correlative studies

Genetic:
• protein expression analysis
Correlative studies

Other:
• enzyme-linked immunosorbent assay
Correlative studies
• laboratory biomarker analysis
Correlative studies

Genetic:
• reverse transcriptase-polymerase chain reaction
Correlative studies

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Case Comprehensive Cancer Center	National Cancer Institute (NCI)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Secondary	Comparison of the expression of COX-1 and COX-2 mRNA in tumor tissues		7-14 days after treatment	No
Secondary	Comparison of levels of PGE2 in tumor tissue		7-14 days after treatment	No
Secondary	Comparison of the expression of COX-1 and COX-2 mRNA in normal colorectal mucosa		7-14 days after treatment	No
Secondary	Comparison of levels of PGE2 in normal colorectal mucosa		7-14 days after treatment	No
Secondary	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	Yes