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

This study has been withdrawn prior to enrollment.
(Slow Accrual)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01403103
First received: July 25, 2011
Last updated: January 16, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
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
Dietary Supplement: cholecalciferol
Procedure: biopsy
Genetic: protein expression analysis
Other: enzyme-linked immunosorbent assay
Other: laboratory biomarker analysis
Genetic: reverse transcriptase-polymerase chain reaction
Phase 0

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

Resource links provided by NLM:


Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:
  • Comparison of the expression of 15-PGDH mRNA and protein levels in tumor tissue [ Time Frame: 7-14 days after treatment ] [ Designated as safety issue: No ]
    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 [ Time Frame: 7-14 days after treatment ] [ Designated as safety issue: No ]
    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:
  • Comparison of the expression of COX-1 and COX-2 mRNA in tumor tissues [ Time Frame: 7-14 days after treatment ] [ Designated as safety issue: No ]
  • Comparison of levels of PGE2 in tumor tissue [ Time Frame: 7-14 days after treatment ] [ Designated as safety issue: No ]
  • Comparison of the expression of COX-1 and COX-2 mRNA in normal colorectal mucosa [ Time Frame: 7-14 days after treatment ] [ Designated as safety issue: No ]
  • Comparison of levels of PGE2 in normal colorectal mucosa [ Time Frame: 7-14 days after treatment ] [ Designated as safety issue: No ]
  • Number of patients with grade 3 related toxicities of a single 100,000 IU dose of 25-OH-vitamin D3 [ Time Frame: 18-25 days after treatment ] [ Designated as safety issue: Yes ]

Enrollment: 0
Study Start Date: April 2012
Study Completion Date: January 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Dietary Supplement: cholecalciferol
Given PO
Other Names:
  • Calciol
  • Vitamin D3
Procedure: biopsy
Correlative studies
Other Name: biopsies
Genetic: protein expression analysis
Correlative studies
Other: enzyme-linked immunosorbent assay
Correlative studies
Other Name: ELISA
Other: laboratory biomarker analysis
Correlative studies
Genetic: reverse transcriptase-polymerase chain reaction
Correlative studies
Other Name: RT-PCR

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01403103

Sponsors and Collaborators
Case Comprehensive Cancer Center
Investigators
Principal Investigator: Smitha Krishnamurthi, MD Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
Principal Investigator: Matthew Kalady, MD Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01403103     History of Changes
Other Study ID Numbers: CASE2210, NCI-2011-01280
Study First Received: July 25, 2011
Last Updated: January 16, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Colorectal Neoplasms
Adenocarcinoma
Rectal Neoplasms
Adenocarcinoma, Mucinous
Cystadenocarcinoma
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Cystic, Mucinous, and Serous
Vitamins
Vitamin D
Ergocalciferols
Cholecalciferol
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on October 16, 2014