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

Tracking Information
First Submitted Date ICMJE	March 31, 2010
First Posted Date ICMJE	April 1, 2010
Last Update Posted Date	November 24, 2017
Actual Study Start Date ICMJE	November 1, 2011
Actual Primary Completion Date	August 2017 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: April 16, 2013)	Change in mammographic density at 12 months compared to baseline [ Time Frame: 12 months ]
Original Primary Outcome Measures ICMJE; (submitted: March 31, 2010)	Change in mammographic density at 12 months compared to baseline
Change History	Complete list of historical versions of study NCT01097278 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: April 16, 2013)	Ki-67 as assessed in tissue obtained in breast biopsies at baseline and at 12 months [ Time Frame: 12 months ]
Original Secondary Outcome Measures ICMJE; (submitted: March 31, 2010)	Ki-67 as assessed in tissue obtained in breast biopsies at baseline and at 12 months
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	S0812 High Dose Cholecalciferol in Premenopausal Women at High-Risk for Breast Cancer
Official Title ICMJE	Phase IIB Randomized Controlled Biomarker Modulation Study of Vitamin D in Premenopausal Women at High Risk for Breast Cancer
Brief 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.
Detailed Description	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.
Study Type ICMJE	Interventional
Study Phase	Not Applicable
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Intervention Model Description: Randomized Phase 2 study Masking: Double (Participant, Investigator); Primary Purpose: Prevention
Condition ICMJE	brca1 Mutation Carrier; brca2 Mutation Carrier; Breast Cancer
Intervention ICMJE	Dietary Supplement: cholecalciferol Given orally; Other: placebo Given orally
Study Arms	Experimental: 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. Intervention: Dietary Supplement: cholecalciferol; Active Comparator: 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. Interventions: Dietary Supplement: cholecalciferol Other: placebo
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: November 21, 2017)	208
Original Estimated Enrollment ICMJE; (submitted: March 31, 2010)	200
Actual Study Completion Date	September 2017
Actual Primary Completion Date	August 2017 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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)
Sex/Gender	Sexes Eligible for Study: Female
Ages	18 Years to 50 Years (Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01097278
Other Study ID Numbers ICMJE	S0812; S0812 ( Other Identifier: SWOG ); U10CA037429 ( U.S. NIH Grant/Contract ); NCI-2011-02032 ( Other Identifier: NCI )
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Southwest Oncology Group
Study Sponsor ICMJE	Southwest Oncology Group
Collaborators ICMJE	National Cancer Institute (NCI)
Investigators ICMJE	Principal Investigator: Katherine D. Crew, MD, MS Columbia University
PRS Account	Southwest Oncology Group
Verification Date	November 2017
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP