A Pilot Study of Low and High Dose Vitamin Cholecalciferol (D3) With Pharmacokinetic and Pharmacodynamic Correlates in Patients With Resected Colon Cancer
18 Years
N/A
Both
Colorectal Cancer
Trial Information
A Pilot Study of Low and High Dose Vitamin Cholecalciferol (D3) With Pharmacokinetic and Pharmacodynamic Correlates in Patients With Resected Colon Cancer
OBJECTIVES:
Primary
- Compare the antiproliferative effects of 2 different doses of cholecalciferol (i.e.,
vitamin D3) in combination with calcium carbonate on the proliferative labeling index
in patients with resected colon cancer.
Secondary
- Compare the effects of these doses on serum levels of 25-OH-D3, 1,25-OH-D3,
24,25-OH-D3, calcium, and parathyroid hormone in these patients.
- Determine the safety of high-dose cholecalciferol in these patients over 2 years.
- Compare the effects of these doses on several biological markers (i.e., cyclin D1,
protein kinase C, vitamin D receptor, p21, and p27) in the rectal mucosa of these
patients.
OUTLINE: This is a randomized, pilot study. Patients are randomized to 1 of 2 treatment
arms.
- Arm I: Patients receive oral low-dose cholecalciferol once daily and oral calcium
carbonate twice daily.
- Arm II: Patients receive oral high-dose cholecalciferol once daily and calcium
carbonate as in arm I.
Treatment in both arms continues for up to 2 years in the absence of disease progression or
unacceptable toxicity. All patients undergo sigmoidoscopy or colonoscopy with 4 quadrant
mucosal biopsies at baseline and after 6 months of study treatment. After their 6-month
mucosal biopsy, patients in arm I switch to high-dose cholecalciferol as in arm II.
Patients undergo blood, urine, and tissue collection periodically during study for
pharmacokinetic, pharmacodynamic, and/or histopathological analysis. Serum is collected
monthly for 3 months and then once every 3 months to assess changes in serum levels of
vitamin D and vitamin D metabolites (i.e., 1,25-OH-D3; 25-OH-D3; 24,25-OH-D3), as well as
changes in calcium and parathyroid hormone, BUN, creatinine, electrolytes, and phosphorus
levels. Urine is collected once every 3 months to assess changes in urine calcium and
creatinine levels for hypercalciuria. Tissue biopsies of normal endorectal mucosa collected
at baseline and after 6 months of study treatment are evaluated by IHC for proliferative
index, vitamin D receptor staining, p21, p27, cyclin D1, and protein kinase C.
PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- History of colon cancer
- Underwent resection and has been in clinical remission for ≥ 1 year
- No inflammatory bowel disease
- No familial adenomatous polyposis
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- Life expectancy > 1 year
- No genitourinary stones within the past 5 years
- No severe comorbid conditions, such as uncompensated heart failure or active
uncontrolled infection
- No history of hypercalcemia
- No active colostomy
- No contraindications to sigmoidoscopy or mucosal biopsies
PRIOR CONCURRENT THERAPY:
- No prior rectal surgery or abdominoperineal resection
- At least 1 month since prior vitamin D or calcium supplementation
- Prior vitamin D supplemental intake ≤ 800 IU per day
- At least 1 year since prior chemotherapy
- No prior radiotherapy to the pelvis
- No concurrent active anticoagulation
- Patients who stop anticoagulation therapy at the time of mucosal biopsy are
eligible
- No other concurrent supplemental calcium or vitamin D
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Primary Purpose: Treatment
Outcome Measure:
Change in proliferative labeling index of normal rectal mucosa as measured by Ki67 IHC staining
Safety Issue:
No
Principal Investigator
Marwan Fakih, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Roswell Park Cancer Institute
Authority:
United States: Federal Government
Study ID:
I 78706
NCT ID:
NCT00470353
Start Date:
September 2006
Completion Date:
September 2009
Related Keywords:
- Colorectal Cancer
- recurrent colon cancer
- stage I colon cancer
- stage II colon cancer
- stage III colon cancer
- Colonic Neoplasms
- Colorectal Neoplasms
Name | Location |
|---|---|
| Roswell Park Cancer Institute | Buffalo, New York 14263 |
