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

Primary Purpose

Mucinous Adenocarcinoma of the Colon, Mucinous Adenocarcinoma of the Rectum, Signet Ring Adenocarcinoma of the Colon

Status
Withdrawn
Phase
Early Phase 1
Locations
Study Type
Interventional
Intervention
cholecalciferol
biopsy
protein expression analysis
enzyme-linked immunosorbent assay
laboratory biomarker analysis
reverse transcriptase-polymerase chain reaction
Sponsored by
Case Comprehensive Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Mucinous Adenocarcinoma of the Colon

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Treatment (chemoprevention)

    Arm Description

    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.

    Outcomes

    Primary Outcome Measures

    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.
    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.

    Secondary Outcome Measures

    Comparison of the expression of COX-1 and COX-2 mRNA in tumor tissues
    Comparison of levels of PGE2 in tumor tissue
    Comparison of the expression of COX-1 and COX-2 mRNA in normal colorectal mucosa
    Comparison of levels of PGE2 in normal colorectal mucosa
    Number of patients with grade 3 related toxicities of a single 100,000 IU dose of 25-OH-vitamin D3

    Full Information

    First Posted
    July 25, 2011
    Last Updated
    January 16, 2014
    Sponsor
    Case Comprehensive Cancer Center
    Collaborators
    National Cancer Institute (NCI)
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01403103
    Brief Title
    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

    2. Study Status

    Record Verification Date
    January 2014
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    Slow Accrual
    Study Start Date
    April 2012 (undefined)
    Primary Completion Date
    January 2014 (Actual)
    Study Completion Date
    January 2014 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Case Comprehensive Cancer Center
    Collaborators
    National Cancer Institute (NCI)

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    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

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Early Phase 1
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Treatment (chemoprevention)
    Arm Type
    Experimental
    Arm Description
    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.
    Intervention Type
    Dietary Supplement
    Intervention Name(s)
    cholecalciferol
    Other Intervention Name(s)
    Calciol, Vitamin D3
    Intervention Description
    Given PO
    Intervention Type
    Procedure
    Intervention Name(s)
    biopsy
    Other Intervention Name(s)
    biopsies
    Intervention Description
    Correlative studies
    Intervention Type
    Genetic
    Intervention Name(s)
    protein expression analysis
    Intervention Description
    Correlative studies
    Intervention Type
    Other
    Intervention Name(s)
    enzyme-linked immunosorbent assay
    Other Intervention Name(s)
    ELISA
    Intervention Description
    Correlative studies
    Intervention Type
    Other
    Intervention Name(s)
    laboratory biomarker analysis
    Intervention Description
    Correlative studies
    Intervention Type
    Genetic
    Intervention Name(s)
    reverse transcriptase-polymerase chain reaction
    Other Intervention Name(s)
    RT-PCR
    Intervention Description
    Correlative studies
    Primary Outcome Measure Information:
    Title
    Comparison of the expression of 15-PGDH mRNA and protein levels in tumor tissue
    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.
    Time Frame
    7-14 days after treatment
    Title
    Comparison of the expression of 15-PGDH mRNA and protein levels in normal colorectal mucosa
    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.
    Time Frame
    7-14 days after treatment
    Secondary Outcome Measure Information:
    Title
    Comparison of the expression of COX-1 and COX-2 mRNA in tumor tissues
    Time Frame
    7-14 days after treatment
    Title
    Comparison of levels of PGE2 in tumor tissue
    Time Frame
    7-14 days after treatment
    Title
    Comparison of the expression of COX-1 and COX-2 mRNA in normal colorectal mucosa
    Time Frame
    7-14 days after treatment
    Title
    Comparison of levels of PGE2 in normal colorectal mucosa
    Time Frame
    7-14 days after treatment
    Title
    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

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Smitha Krishnamurthi, MD
    Organizational Affiliation
    Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
    Official's Role
    Principal Investigator
    First Name & Middle Initial & Last Name & Degree
    Matthew Kalady, MD
    Organizational Affiliation
    Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Learn more about this trial

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

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