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Study of Vitamin D for Premenopausal Women at High Risk for Breast Cancer

This study has been completed.
Sponsor:
Collaborator:
Prevent Cancer Foundation
Information provided by (Responsible Party):
Katherine D. Crew, Columbia University
ClinicalTrials.gov Identifier:
NCT00976339
First received: September 11, 2009
Last updated: June 20, 2016
Last verified: May 2016
  Purpose
This proposal is for a pilot study of 20 premenopausal women at high risk for breast cancer development who will receive high dose vitamin D3, cholecalciferol 20,000 IU (2 capsules) weekly, for 1 year. The primary objective of this study is to determine the feasibility of a 1-year intervention of vitamin D in this study population. Secondary objectives include evaluating the biologic effects of vitamin D.

Condition Intervention
Breast Cancer
Drug: Cholecalciferol

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Pilot Biomarker Modulation Study of Vitamin D in Premenopausal Women at High Risk for Breast Cancer

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • Number of Participants That Successfully Completed the 1-year Intervention [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Enrollment: 20
Study Start Date: September 2007
Study Completion Date: December 2013
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cholecalciferol 20,000 IU
Participants will receive Cholecalciferol 20,000 IU (2 capsules) weekly for one year.
Drug: Cholecalciferol

Cholecalciferol is a vitamin D3. Vitamin D is important for the absorption of calcium from the stomach and for the functioning of calcium in the body. Cholecalciferol is used to treat or prevent many conditions caused by a lack of vitamin D.

Cholecalciferol will be available in gel capsule form at 10,000 IU (0.25 mg cholecalciferol) each.

Other Name: Vitamin D3
Experimental: Cholecalciferol 30,000 IU
Participants will receive Cholecalciferol 30,000 IU (3 capsules) weekly for one year.
Drug: Cholecalciferol

Cholecalciferol is a vitamin D3. Vitamin D is important for the absorption of calcium from the stomach and for the functioning of calcium in the body. Cholecalciferol is used to treat or prevent many conditions caused by a lack of vitamin D.

Cholecalciferol will be available in gel capsule form at 10,000 IU (0.25 mg cholecalciferol) each.

Other Name: Vitamin D3

Detailed Description:

Despite significant advances in the early detection and treatment of breast cancer, it is still the most common cancer among women in the U.S. and up to 25% will die of their disease. Therefore, more attention has focused on primary prevention to reduce breast cancer-related morbidity and mortality. Due to the limited number of significant modifiable risk factors for breast cancer, researchers are exploring the potential of chemoprevention to arrest or reverse cancer development with a drug intervention. Currently, tamoxifen is the only FDA-approved drug for breast cancer risk reduction. However, tamoxifen's adverse effects have limited its usage. It is anticipated that raloxifene will be used more, as it has a more favorable side effect profile. However, tamoxifen and raloxifene do not prevent estrogen receptor (ER)-negative breast tumors, which account for about a third of all breast cancers and are associated with a poorer prognosis. Current priorities in breast cancer chemoprevention are to identify preventive agents which may be effective against ER-negative breast cancers, and have a low risk of side-effects.

Vitamin D is a fat-soluble vitamin which is produced in the body and may come from food sources. Epidemiologic studies suggest that vitamin D may influence breast cancer development, which has resulted in increased interest in the use of vitamin D for the treatment and prevention of breast cancer. Numerous experimental studies have shown that vitamin D compounds have anti-carcinogenic properties against breast cancer. Given the epidemiologic data and the extensive preclinical evidence of the anti-tumor effects of vitamin D, it is therefore reasonable to test the biological effects of high-dose vitamin D in early phase clinical trials. The investigators hypothesize that vitamin D3, cholecalciferol, will modulate biomarkers of breast cancer risk.

  Eligibility

Ages Eligible for Study:   21 Years and older   (Adult, Senior)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Elevated risk of breast cancer defined as having at least one of the following: (1) Predicted 5-year modified Gail model risk of 1.7% or greater, (2) Lobular carcinoma in situ, (3) Known BRCA1 or BRCA2 deleterious mutation carrier, (4) Prior history of ductal carcinoma in situ, if no current tamoxifen use or prior radiation to the contralateral breast.
  • Age 21 years or older.
  • Premenopausal defined as < 6 months since the last menstrual period, no prior bilateral oophorectomy, not on estrogen replacement, and serum FSH values consistent with institutional normal values for the premenopausal state.
  • Normal breast exam and mammogram (BIRADS score of 1 or 2).
  • Baseline mammographic density ≥25% as assessed qualitatively by the mammographer (25-50% = "scattered fibroglandular densities"; >50-75% = "heterogeneously dense breasts"; >75% = "extremely dense breasts").
  • Baseline serum 25-hydroxyvitamin D <32 ng/ml.
  • Prior tamoxifen use is allowed provided treatment is discontinued at least 28 days prior to enrollment.
  • Willingness to allow submission of core needle breast biopsy for pathology review and collection of blood for biomarker analysis and banking.
  • At least one breast available for imaging and biopsy.
  • Willingness to not take calcium or vitamin D supplements during the one year intervention, due to the potential risk of hypercalcemia/hypercalciuria with high dose vitamin D. Premenopausal women who need to take calcium supplementation for any medical condition will be excluded from the study. Dietary restrictions on calcium intake may be imposed if the subject is found to have borderline high serum or urine levels of calcium during the study intervention and a list of dietary sources of calcium will be provided.
  • Normal serum calcium.
  • No history of kidney stones.
  • Adequate renal and hepatic function: serum creatinine, bilirubin, AST, ALT and alkaline phosphatase < 2.0 x the institutional upper limit of normal (IULN).
  • No hypersensitivity reactions to vitamin D.
  • Zubrod performance status of 0 or 1.
  • Not pregnant or nursing.
  • Agree to use effective contraception, hormone-based oral contraceptives allowed but switching birth control methods is discouraged while on-study.
  • No significant medical or psychiatric condition that would preclude study completion.

Exclusion Criteria:

  • Not meeting one or any of inclusion criteria
  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: NCT00976339

Locations
United States, New York
Columbia University Medical Center Herbert Irving Cancer Center
New York, New York, United States, 10032
Sponsors and Collaborators
Katherine D. Crew
Prevent Cancer Foundation
Investigators
Principal Investigator: Katherine Crew, MD Columbia University
  More Information

Publications:
Hershman, D. L., McMahon, D., Irani, D., Cucchiara, G., Crew, K. D., Raptis, G., and Shane, E. High prevalence of vitamin D deficiency in premenopausal women with early-stage breast cancer. Proc Am Soc Clin Oncol, pp. Abst #8568. Atlanta, 2006.
Chlebowski, R. T., Johnson, K. C., Kooperberg, C., Hubbell, A., Lane, D., O'Sullivan, M., Cummings, S., Rohan, T., Khandekar, J., and Investigators, T. W. s. H. I. The Women's Health Initiative randomized trial of calcium plus vitamin D: effects on breast cancer and arthralgias. Proceedings of the American Society of Clinical Oncology 24, pp. LBA6. Atlanta, 2006.

Responsible Party: Katherine D. Crew, Florence Irving Assistant Professor of Medicine and Assistant Professor of Epidemiology, Columbia University
ClinicalTrials.gov Identifier: NCT00976339     History of Changes
Other Study ID Numbers: AAAC3089 
Study First Received: September 11, 2009
Results First Received: July 27, 2015
Last Updated: June 20, 2016
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
Individual Participant Data  
Plan to Share IPD: Undecided

Keywords provided by Columbia University:
Breast cancer
Vitamin D
Premenopausal

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Vitamins
Vitamin D
Ergocalciferols
Cholecalciferol
Micronutrients
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on September 29, 2016