Clinical trial NCT01403103: Cholecalciferol(25-[OH]-Vitamin D) in Treating Patients With Colorectal Cancer
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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: EARLY_PHASE1
Conditions: 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
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2011-07-27
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Comparison of the expression of 15-PGDH mRNA and protein levels in tumor tissue
timeFrame: 7-14 days after treatment
measure: Comparison of the expression of 15-PGDH mRNA and protein levels in normal colorectal mucosa
timeFrame: 7-14 days after treatment
Secondary outcomes:
measure: Comparison of the expression of COX-1 and COX-2 mRNA in tumor tissues
timeFrame: 7-14 days after treatment
measure: Comparison of levels of PGE2 in tumor tissue
timeFrame: 7-14 days after treatment
measure: Comparison of the expression of COX-1 and COX-2 mRNA in normal colorectal mucosa
timeFrame: 7-14 days after treatment
measure: Comparison of levels of PGE2 in normal colorectal mucosa
timeFrame: 7-14 days after treatment
measure: Number of patients with grade 3 related toxicities of a single 100,000 IU dose of 25-OH-vitamin D3
timeFrame: 18-25 days after treatment
Other outcomes:
Locations:
Study officials:
affiliation: Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
name: Smitha Krishnamurthi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
name: Matthew Kalady, MD
role: PRINCIPAL_INVESTIGATOR
References: