Vitamin D in Postmenopausal Women at High Risk for Breast Cancer

NCT ID: NCT00859651

Last Updated: 2017-09-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-06-30
• Study Completion Date: 2015-04-30

Brief Summary

This is a phase II study which will enroll 20 postmenopausal women who are at high risk for breast cancer development. The goal is to determine whether a one-year intervention of high-dose vitamin D at 2 different doses (20,000 IU weekly or 30,000 IU weekly) will increase circulating blood levels of vitamin D and to obtain preliminary data on the biologic effects of vitamin D for breast cancer prevention.

Detailed Description

Participants will receive oral vitamin D3, cholecalciferol 20,000 IU or 30,000 IU weekly. Before beginning the intervention, the participants will have a general physical exam including a clinical breast exam and anthropometric measures, a morning blood draw (for analysis of 25(OH)D, 1,25(OH)D, parathyroid hormone (PTH), insulin-like growth factor (IGF)-I, insulin-like growth factor-binding protein 3 (IGFBP-3), estradiol, estrone, testosterone, and sex hormone-binding globulin (SHBG) at baseline, 6 months, and 12 months) and a bilateral mammogram (at baseline and 12 months). Participants will also complete a baseline questionnaire, collecting data on demographic information and breast cancer risk factors. In addition, we will be collecting data on vitamin D sources from diet and sunlight exposure using a validated questionnaire administered at baseline and 12 months.

For follow-up visits, the participant will be seen at the study site at months 3, 6, 9, and 12. During these visits, drug will be dispensed, adherence ascertained, and adverse events will also be assessed. In addition, blood (serum calcium, albumin, creatinine) and urine (urine calcium, creatinine) will be collected to monitor for toxicity. A 24-hour urine collection will be conducted at baseline and 12 months to assess for hypercalciuria. After the 1 year intervention, all participants will have a complete physical exam including clinical breast exam, a bilateral mammogram, blood draw, and complete a follow-up questionnaire.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

20,000 IU weekly

Postmenopausal women who are at increased risk for breast cancer development receiving vitamin D3, oral cholecalciferol 20,000 IU weekly, for one year.

Cholecalciferol 20,000 IU (2 active capsules + 1 matching placebo capsule)

Group Type: ACTIVE_COMPARATOR

Cholecalciferol

Intervention Type: DRUG

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.

Placebo capsule

Intervention Type: DRUG

Matching placebo capsules

30,000 IU weekly

Postmenopausal women who are at increased risk for breast cancer development receiving vitamin D3, oral cholecalciferol 30,000 IU weekly, for one year.

Cholecalciferol 30,000 IU (3 active capsules)

Group Type: ACTIVE_COMPARATOR

Cholecalciferol

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Placebo capsule

Matching placebo capsules

Intervention Type: DRUG

Other Intervention Names

Vitamin D3; Placebo

Eligibility 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 1.67% 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.
• Postmenopausal defined as > 6 months since the last menstrual period, prior bilateral oophorectomy, or serum follicle-stimulating hormone (FSH)/luteinizing hormone (LH) values consistent with institutional normal values for the postmenopausal state.
• 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.
• Normal breast exam and mammogram (Breast Imaging Reporting and Data System (BIRADS) score of 1 or 2) or abnormal breast imaging with a benign breast biopsy without evidence of cancer. Normal baseline breast magnetic resonance imaging (MRI) (BIRADS score of 1, 2, or 3).
• Prior tamoxifen or raloxifene use is allowed provided treatment is discontinued at least 28 days prior to enrollment.
• At least one breast available for imaging. No bilateral breast implants.
• Willingness to not take vitamin D supplements during the one year intervention, but up to 1000mg of calcium supplementation is allowed.
• Normal serum calcium.
• Adequate renal and hepatic function: serum creatinine, bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase < 2.0 x the institutional upper limit of normal (IULN).
• Performance status of 0 or 1.

Exclusion Criteria

• Other prior malignancy. The following is allowed: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the participant is currently in complete remission, or any other cancer (including breast cancer) for which the participant has been disease-free for 5 years.
• History of kidney stones.
• Hypersensitivity reactions to vitamin D.
• On estrogen replacement therapy.
• Significant medical or psychiatric condition that would preclude study completion.

• Minimum Eligible Age: 21 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Avon Foundation

OTHER

Sponsor Role: collaborator

Columbia University

OTHER

Sponsor Role: lead

Responsible Party

Katherine D. Crew

Associate Professor of Medicine and Associate Professor of Epidemiology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Katherine D Crew, MD, MS

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

Columbia University

New York, New York, United States

Countries

United States

Other Identifiers

AAAD3638

Identifier Type: -

Identifier Source: org_study_id