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NCT01097278

S0812 High Dose Cholecalciferol in Premenopausal Women at High-Risk for Breast Cancer

Last Updated: 2017-11-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

Total Enrollment

208 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-11-01

Study Completion Date

2017-09-30

Brief Summary

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RATIONALE: Cholecalciferol may prevent breast cancer in premenopausal women.

PURPOSE: This randomized phase II trial is studying how well cholecalciferol works in preventing breast cancer in premenopausal women.

Detailed Description

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OBJECTIVES:

* To assess whether mammographic density is reduced in premenopausal women at high risk of breast cancer taking high-dose vitamin D3 (oral cholecalciferol 20,000 IU weekly) vs placebo for 1 year.
* To assess whether proliferation as measured by Ki-67 staining of breast epithelial cells is reduced in women receiving these treatments.
* To explore the difference in the expression of other biomarkers (including cleaved caspase-3 \[apoptosis marker\], ER, vitamin D receptor \[VDR\], and 1α-hydroxylase) in breast tissue obtained from these women.
* To assess whether parathyroid hormone, IGF-1, IGFBP-3, 25(OH)D, and 1,25(OH)D serum levels are altered in these women at baseline and at 6 and 12 months.
* To explore whether a change in mammographic density correlates with polymorphisms in the VDR gene.
* To assess other sources of vitamin D (sunlight exposure, diet) in these women using a validated questionnaire administered at baseline and at 12 and 24 months.
* To collect and bank serum, plasma, and breast tissue from these women before and after a 1-year intervention with vitamin D for future biomarker analysis.
* To assess the toxicity of high-dose cholecalciferol compared to placebo in this setting.

OUTLINE: This is a multicenter study. Participants are stratified according to baseline serum 25(OH)D level (\< 20 ng/mL vs 20-32 ng/mL or \< 50 nmol/L vs 50-80 nmol/L), baseline mammographic density (11-50% vs \> 50%), and designated biopsy site (yes vs no). Participants are randomized to 1 of 2 treatment arms.

* Arm I: Participants receive oral cholecalciferol once weekly and oral vitamin D once daily. Treatment repeats for 12 months in the absence of evidence of cancer or unacceptable toxicity.
* Arm II: Participants receive oral placebo once weekly and oral vitamin D once daily. Treatment repeats for 12 months in the absence of evidence of cancer or unacceptable toxicity.

Blood samples are collected at baseline and periodically thereafter for biomarkers and 25(OH)D level. Participants undergo a mammogram at baseline and at 12 months. Participants may also undergo random core-needle breast biopsy at baseline and at 12 months.

Participants complete a questionnaire at baseline and at 12 and 24 months.

After completion of study therapy, participants are followed up at 1 and 12 months.

Conditions

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brca1 Mutation Carrier brca2 Mutation Carrier Breast Cancer

Keywords

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breast cancer ductal breast carcinoma in situ lobular breast carcinoma in situ BRCA1 mutation carrier BRCA2 mutation carrier

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Randomized Phase 2 study

Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Arm I

Participants receive oral cholecalciferol once weekly and oral vitamin D once daily. Treatment repeats for 12 months in the absence of evidence of cancer or unacceptable toxicity.

Group Type EXPERIMENTAL

cholecalciferol

Intervention Type DIETARY_SUPPLEMENT

Given orally

Arm II

Participants receive oral placebo once weekly and oral vitamin D once daily. Treatment repeats for 12 months in the absence of evidence of cancer or unacceptable toxicity.

Group Type ACTIVE_COMPARATOR

cholecalciferol

Intervention Type DIETARY_SUPPLEMENT

Given orally

placebo

Intervention Type OTHER

Given orally

Interventions

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cholecalciferol

Given orally

Intervention Type DIETARY_SUPPLEMENT

placebo

Given orally

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Modified Gail Model/CARE model\*\* risk at 5 years ≥ 1.67% or lifetime risk ≥ 20% by Claus, BRCAPro, Tyrer-Cuzick or IBIS models OR
* Mammographic density ≥ 50% (heterogenously dense) NOTE: \*\*Risk models are to be used only if there is no known previous diagnosis of resected DCIS or LCIS and there is no known deleterious mutation in BRCA1, BRCA2, PTEN, or TP53.
* At least one breast available for imaging and biopsy (a previously irradiated breast \[i.e., for resected DCIS\] is not evaluable for breast imaging or biopsy)
* Baseline mammogram (performed within 10 days after starting their last menstrual period on a digital mammography machine) that shows either normal or benign findings

* Baseline mammographic density \> 10% based upon the classification system (2 = 11-50%, "scattered fibroglandular densities"; 3 = 51-75%, "heterogeneously dense"; 4 = \>75, "extremely dense". Women with a baseline mammographic density of ≤ 10% (1 = ≤ 10% breasts are almost entirely fat)will not be eligible.

PATIENT CHARACTERISTICS:

* Premenopausal, defined as ≥ 1 of the following criteria:

* Less than 6 months since the last menstrual period, no prior bilateral oophorectomy, and no use of hormone-replacement therapy
* Has undergone a prior hysterectomy but no prior bilateral oophorectomy AND follicle-stimulating hormone values measured within the past 28 days are consistent with the normal values for the premenopausal state
* Zubrod performance status 0-1
* Serum creatinine ≤ upper limit of normal (ULN)
* Serum calcium or corrected calcium ≤ ULN
* Spot urine calcium:creatinine ratio \< 0.37 mg/dL
* INR ≤ 1.5 times ULN+
* PT and PTT ≤ ULN\*
* Baseline serum 25(OH)D level ≤ 32 ng/mL (or 80 nmol/L)
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No other prior malignancy except for the following:

* Adequately treated basal cell or squamous cell skin cancer
* In situ cervical cancer
* Adequately treated stage I or II (including resected Stage I, T1b-c N0-N1mi through Stage II breast cancer) from which the participant is currently in complete remission
* Any other cancer (including contralateral breast) for which the participant has been disease-free for ≥ 5 years
* No history of kidney stones
* No medical conditions requiring calcium or vitamin D supplementation (i.e., osteoporosis)
* No known hypersensitivity to vitamin D
* No known allergy to soy NOTE: +For patients undergoing breast biopsy.

PRIOR CONCURRENT THERAPY:

* Prior breast reduction surgery allowed

* No bilateral breast implants
* More than 1 month since prior surgery or radiotherapy to the breast for resected DCIS
* At least 28 days since prior tamoxifen
* Prior anticoagulant therapy allowed provided it is discontinued ≥ 7 days before breast biopsy
* No concurrent calcium or additional vitamin D supplements

* Concurrent multivitamins allowed provided that the dose of vitamin D in the multivitamin does not exceed 400 IU daily
* No concurrent participation in any other clinical trial for the treatment or prevention of cancer unless the participant is no longer receiving the intervention and is in the follow-up phase only (participants must not join such a trial while participating in this study)

Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Katherine D. Crew, MD, MS

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

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Northeast Alabama Regional Medical Center

Anniston, Alabama, United States

Site Status

Providence Hospital

Mobile, Alabama, United States

Site Status

Alaska Breast Care and Surgery LLC

Anchorage, Alaska, United States

Site Status

Alaska Regional Hospital

Anchorage, Alaska, United States

Site Status

Alaska Women's Cancer Care

Anchorage, Alaska, United States

Site Status

Anchorage Oncology Centre

Anchorage, Alaska, United States

Site Status

Katmai Oncology Group

Anchorage, Alaska, United States

Site Status

Providence Alaska Medical Center

Anchorage, Alaska, United States

Site Status

Fairbanks Memorial Hospital

Fairbanks, Alaska, United States

Site Status

University of Arizona Cancer Center-North Campus

Tucson, Arizona, United States

Site Status

The University of Arizona Medical Center-University Campus

Tucson, Arizona, United States

Site Status

Highlands Oncology Group-Rogers

Rogers, Arkansas, United States

Site Status

East Bay Radiation Oncology Center

Castro Valley, California, United States

Site Status

Valley Medical Oncology Consultants-Castro Valley

Castro Valley, California, United States

Site Status

John Muir Medical Center-Concord Campus

Concord, California, United States

Site Status

UC Irvine Health Cancer Center-Newport

Costa Mesa, California, United States

Site Status

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Site Status

Epic Care-Dublin

Dublin, California, United States

Site Status

Bay Area Breast Surgeons Inc

Emeryville, California, United States

Site Status

Epic Care Partners in Cancer Care

Emeryville, California, United States

Site Status

Valley Medical Oncology Consultants-Fremont

Fremont, California, United States

Site Status

Los Angeles County-USC Medical Center

Los Angeles, California, United States

Site Status

USC / Norris Comprehensive Cancer Center

Los Angeles, California, United States

Site Status

Contra Costa Regional Medical Center

Martinez, California, United States

Site Status

El Camino Hospital

Mountain View, California, United States

Site Status

Highland General Hospital

Oakland, California, United States

Site Status

Alta Bates Summit Medical Center - Summit Campus

Oakland, California, United States

Site Status

Bay Area Tumor Institute

Oakland, California, United States

Site Status

Hematology and Oncology Associates-Oakland

Oakland, California, United States

Site Status

Tom K Lee Inc

Oakland, California, United States

Site Status

UC Irvine Health/Chao Family Comprehensive Cancer Center

Orange, California, United States

Site Status

Huntington Memorial Hospital

Pasadena, California, United States

Site Status

East Bay Medical Oncology Hematology Medical Associates Inc-Pleasant Hill

Pleasant Hill, California, United States

Site Status

Valley Medical Oncology Consultants

Pleasanton, California, United States

Site Status

Doctors Medical Center- JC Robinson Regional Cancer Center

San Pablo, California, United States

Site Status

Breastlink Medical Group Inc

Santa Ana, California, United States

Site Status

John Muir Medical Center-Walnut Creek

Walnut Creek, California, United States

Site Status

Presbyterian Intercommunity Hospital

Whittier, California, United States

Site Status

The Medical Center of Aurora

Aurora, Colorado, United States

Site Status

Boulder Community Hospital

Boulder, Colorado, United States

Site Status

Rocky Mountain Cancer Centers-Boulder

Boulder, Colorado, United States

Site Status

Penrose-Saint Francis Healthcare

Colorado Springs, Colorado, United States

Site Status