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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


Phase 0
18 Years
N/A
Open (Enrolling)
Both
Mucinous Adenocarcinoma of the Colon, Mucinous Adenocarcinoma of the Rectum, Signet Ring Adenocarcinoma of the Colon, Signet Ring Adenocarcinoma of the Rectum, Stage I Colon Cancer, Stage I Rectal Cancer

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Trial Information

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


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.


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

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Comparison of the expression of 15-PGDH mRNA and protein levels in tumor tissue

Outcome Description:

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.

Outcome Time Frame:

7-14 days after treatment

Safety Issue:

No

Principal Investigator

Smitha Krishnamurthi, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Authority:

United States: Federal Government

Study ID:

CASE2210

NCT ID:

NCT01403103

Start Date:

April 2012

Completion Date:

Related Keywords:

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

Name

Location

Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer CenterCleveland, Ohio  44106-5065
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer CenterCleveland, Ohio  44195