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


N/A
18 Years
N/A
Not Enrolling
Both
Colorectal Cancer

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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