Know Cancer

forgot password

A Pilot Study of Low and High Dose Vitamin Cholecalciferol (D3) With Pharmacokinetic and Pharmacodynamic Correlates in Patients With Resected Colon Cancer

18 Years
Not Enrolling
Colorectal Cancer

Thank you

Trial Information

A Pilot Study of Low and High Dose Vitamin Cholecalciferol (D3) With Pharmacokinetic and Pharmacodynamic Correlates in Patients With Resected Colon Cancer



- 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.


- 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

OUTLINE: This is a randomized, pilot study. Patients are randomized to 1 of 2 treatment

- 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


- History of colon cancer

- Underwent resection and has been in clinical remission for ≥ 1 year

- No inflammatory bowel disease

- No familial adenomatous polyposis


- 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


- 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

- No other concurrent supplemental calcium or vitamin D

Type of Study:


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:


Principal Investigator

Marwan Fakih, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Roswell Park Cancer Institute


United States: Federal Government

Study ID:

I 78706



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



Roswell Park Cancer Institute Buffalo, New York  14263