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Clinical Trials (PDQ®)

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

Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IIBiomarker/Laboratory analysis, PreventionActive18 to 50NCI, OtherS0812
U10CA037429, NCI-2011-02032, SWOG-S0812, NCT01097278

Trial Description

Summary

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.

Further Study Information

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.

Eligibility Criteria

DISEASE CHARACTERISTICS:

  • At an elevated risk of breast cancer by at least one of the following criteria:
  • Diagnosis of ADH, ALH, lobular carcinoma in situ (LCIS) or resected ductal carcinoma in situ (DCIS) or small invasive breast cancers (pTmi or pT1a N0) if no pior RT, tamoxifen, or systemic breast cancer treatment within 28 days prior to registration OR diagnosis of resected Stage I (T1b-c N0-N1mi) through Stage II breast cancer for which the participant has been disease-free for at least 5 years and has completed all adjuvant treatment OR
  • A known* deleterious mutation in BRCA1, BRCA2, PTEN, or TP53 NOTE: *The participant must be a documented carrier to meet this criterion. If there is a known mutation in a hereditary breast cancer susceptibility gene in a participant's family member, the participant herself must have undergone genetic testing as per NCCN clinical guidelines to be eligible per this criterion.
  • 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)

Trial Contact Information

Trial Lead Organizations/Sponsors

Southwest Oncology Group

National Cancer Institute

Katherine D. Crew, MD, MSPrincipal Investigator

Patricia O'KanePh: 2106148808 Ext.1011
  Email: pokane@swog.org

Trial Sites

U.S.A.
Alabama
  Mobile
 Providence Cancer Center at Providence Hospital
 Thaddeus A Beeker Ph: 877-904-4367
California
  Dublin
 Epic Care-Dublin
 James H. Feusner Ph: 510-450-7600
  Pleasant Hill
 East Bay Medical Oncology Hematology Associates - Pleasant Hill
 James H. Feusner Ph: 510-450-7600
Illinois
  Decatur
 CCOP - Central Illinois
 Katherine D Crew
  Galesburg
 Medical and Surgical Specialists, LLC
 Nguyet A Le-Lindqwister Ph: 800-793-2262
New Mexico
  Albuquerque
 Presbyterian Cancer Treatment Center at Presbyterian Kaseman Hospital
 Melanie E. Royce Ph: 505-727-8000
North Carolina
  Winston-Salem
 CCOP - Southeast Cancer Control Consortium
 Katherine D Crew Ph: 212-305-1732
  Email: kd59@columbia.edu
South Carolina
  Anderson
 AnMed Cancer Center
 James Dewitt Bearden Ph: 800-486-5941

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01097278
ClinicalTrials.gov processed this data on November 12, 2014

Note: Information about this trial is from the ClinicalTrials.gov database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the ClinicalTrials.gov record to standardize the names of study sponsors, sites, and contacts. Cancer.gov only lists sites that are recruiting patients for active trials, whereas ClinicalTrials.gov lists all sites for all trials. Questions and comments regarding the presented information should be directed to ClinicalTrials.gov.

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