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Phase IIB Randomized Controlled Biomarker Modulation Study of Vitamin D in Premenopausal Women at High Risk for Breast Cancer


Phase 2
18 Years
50 Years
Open (Enrolling)
Female
brca1 Mutation Carrier, brca2 Mutation Carrier, Breast Cancer

Thank you

Trial Information

Phase IIB Randomized Controlled Biomarker Modulation Study of Vitamin D in Premenopausal Women at High Risk for Breast Cancer


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.

Inclusion 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)

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Outcome Measure:

Change in mammographic density at 12 months compared to baseline

Outcome Time Frame:

12 months

Safety Issue:

No

Principal Investigator

Laurence H. Baker, DO, FACOI

Investigator Role:

Principal Investigator

Investigator Affiliation:

Southwest Oncology Group - Group Chair's Office

Authority:

United States: Food and Drug Administration

Study ID:

CDR0000668698

NCT ID:

NCT01097278

Start Date:

November 2011

Completion Date:

July 2015

Related Keywords:

  • brca1 Mutation Carrier
  • brca2 Mutation Carrier
  • Breast Cancer
  • breast cancer
  • ductal breast carcinoma in situ
  • lobular breast carcinoma in situ
  • BRCA1 mutation carrier
  • BRCA2 mutation carrier
  • Breast Neoplasms

Name

Location

Cardinal Bernardin Cancer Center at Loyola University Medical CenterMaywood, Illinois  60153-5500
CCOP - Upstate CarolinaSpartanburg, South Carolina  29303
Tripler Army Medical CenterHonolulu, Hawaii  96859-5000
CCOP - WichitaWichita, Kansas  67214-3882
Hurley Medical CenterFlint, Michigan  48503
CCOP - Michigan Cancer Research ConsortiumAnn Arbor, Michigan  48106
Saint Joseph Mercy Cancer CenterAnn Arbor, Michigan  48106-0995
Oakwood Cancer Center at Oakwood Hospital and Medical CenterDearborn, Michigan  48123-2500
Genesys Hurley Cancer InstituteFlint, Michigan  48503
Van Elslander Cancer Center at St. John Hospital and Medical CenterGrosse Pointe Woods, Michigan  48236
Sparrow Regional Cancer CenterLansing, Michigan  48912-1811
St. John Macomb HospitalWarren, Michigan  48093
CCOP - Bay Area Tumor InstituteOakland, California  94609-3305
CCOP - Cancer Research for the OzarksSpringfield, Missouri  65807
CCOP - Montana Cancer ConsortiumBillings, Montana  59101
CCOP - ColumbusColumbus, Ohio  43206
CCOP - GreenvilleGreenville, South Carolina  29615
CCOP - Columbia River Oncology ProgramPortland, Oregon  97225
Cancer Research Center of HawaiiHonolulu, Hawaii  96813
CCOP - St. Louis-Cape GirardeauSaint Louis, Missouri  63141
City of Hope Comprehensive Cancer CenterDuarte, California  91010
Arizona Cancer Center at University of Arizona Health Sciences CenterTucson, Arizona  85724
Josephine Ford Cancer Center at Henry Ford HospitalDetroit, Michigan  48202
Hulston Cancer Center at Cox Medical Center SouthSpringfield, Missouri  65807
St. John's Regional Health CenterSpringfield, Missouri  65804
Winthrop University HospitalMineola, New York  11501
McDowell Cancer Center at Akron General Medical CenterAkron, Ohio  44307
Central Baptist HospitalLexington, Kentucky  40503
Via Christi Cancer Center at Via Christi Regional Medical CenterWichita, Kansas  67214
Lahey Clinic Medical Center - BurlingtonBurlington, Massachusetts  01805
James P. Wilmot Cancer Center at University of Rochester Medical CenterRochester, New York  14642
Alaska Regional Hospital Cancer CenterAnchorage, Alaska  99508
Good Samaritan Regional Health CenterMt. Vernon, Illinois  62864
William Beaumont Hospital - Royal Oak CampusRoyal Oak, Michigan  48073
David C. Pratt Cancer Center at St. John's MercySt. Louis, Missouri  63141
Hematology-Oncology Centers of the Northern Rockies - BillingsBillings, Montana  59101
St. Peter's HospitalHelena, Montana  59601
Kalispell Regional Medical CenterKalispell, Montana  59901
Glacier Oncology, PLLCKalispell, Montana  59901
Montana Cancer Center at St. Patrick Hospital and Health Sciences CenterMissoula, Montana  59802
Montana Cancer Specialists at Montana Cancer CenterMissoula, Montana  59802
Adena Regional Medical CenterChillicothe, Ohio  54601
Doctors Hospital at Ohio HealthColumbus, Ohio  43228
Riverside Methodist Hospital Cancer CareColumbus, Ohio  43214
Grady Memorial HospitalDelaware, Ohio  43015
Fairfield Medical CenterLancaster, Ohio  43130
Strecker Cancer Center at Marietta Memorial HospitalMarietta, Ohio  45750
Licking Memorial Cancer Care Program at Licking Memorial HospitalNewark, Ohio  43055
Community Hospital of Springfield and Clark CountySpringfield, Ohio  45505
Genesis - Good Samaritan HospitalZanesville, Ohio  43701
Mountain States Tumor Institute at St. Luke's Regional Medical CenterBoise, Idaho  83712-6297
University of New Mexico Cancer CenterAlbuquerque, New Mexico  87131-5636
Herbert Irving Comprehensive Cancer Center at Columbia University Medical CenterNew York, New York  10032
Legacy Emanuel Hospital and Health Center and Children's HospitalPortland, Oregon  97227
M. D. Anderson Cancer Center at University of TexasHouston, Texas  77030-4009
Chao Family Comprehensive Cancer Center at University of California Irvine Medical CenterOrange, California  92868
Huntsman Cancer Institute at University of UtahSalt Lake City, Utah  84112
Decatur Memorial Hospital Cancer Care InstituteDecatur, Illinois  62526
Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical CenterHartford, Connecticut  06105
Mount Carmel Health - West HospitalColumbus, Ohio  43222
Front Range Cancer SpecialistsFort Collins, Colorado  80528
Alta Bates Summit Medical Center - Summit CampusOakland, California  94609
Poudre Valley HospitalFort Collins, Colorado  80524
Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical CenterBoise, Idaho  83706
Cancer Center of Kansas, PA - Dodge CityDodge City, Kansas  67801
Feist-Weiller Cancer Center at Louisiana State University Health SciencesShreveport, Louisiana  71130-3932
Saint Francis Medical CenterCape Girardeau, Missouri  63701
Highland Hospital of RochesterRochester, New York  14620
Legacy Mount Hood Medical CenterGresham, Oregon  97030
Providence Milwaukie HospitalMilwaukie, Oregon  97222
Providence Cancer Center at Providence Portland Medical CenterPortland, Oregon  97213-2967
Providence St. Vincent Medical CenterPortland, Oregon  97225
Legacy Meridian Park HospitalTualatin, Oregon  97062
Bon Secours St. Francis Health SystemGreenville, South Carolina  29601
Southwest Washington Medical Center Cancer CenterVancouver, Washington  98668
Highland General HospitalOakland, California  94602
Regional Cancer Center at Singing River HospitalPascagoula, Mississippi  39581
Cancer Center of Kansas, PA - ChanuteChanute, Kansas  66720
Cancer Center of Kansas - Fort ScottFort Scott, Kansas  66701
Cancer Center of Kansas-IndependenceIndependence, Kansas  67301
Cancer Center of Kansas, PA - KingmanKingman, Kansas  67068
Lawrence Memorial HospitalLawrence, Kansas  66044
Cancer Center of Kansas, PA - LiberalLiberal, Kansas  67905
Cancer Center of Kansas, PA - NewtonNewton, Kansas  67114
Cancer Center of Kansas, PA - ParsonsParsons, Kansas  67357
Cancer Center of Kansas, PA - PrattPratt, Kansas  67124
Cancer Center of Kansas, PA - SalinaSalina, Kansas  67401
Cancer Center of Kansas, PA - WellingtonWellington, Kansas  67152
Cancer Center of Kansas, PA - WichitaWichita, Kansas  67214
Associates in Womens Health, PA - North ReviewWichita, Kansas  67208
Cancer Center of Kansas, PA - Medical Arts TowerWichita, Kansas  67208
Cancer Center of Kansas, PA - WinfieldWinfield, Kansas  67156
Foote Memorial HospitalJackson, Michigan  49201
St. Mary Mercy HospitalLivonia, Michigan  48154
St. Joseph Mercy OaklandPontiac, Michigan  48341-2985
Mercy Regional Cancer Center at Mercy HospitalPort Huron, Michigan  48060
Seton Cancer Institute at Saint Mary's - SaginawSaginaw, Michigan  48601
Billings Clinic - DowntownBillings, Montana  59107-7000
Bozeman Deaconess Cancer CenterBozeman, Montana  59715
Great Falls Clinic - Main FacilityGreat Falls, Montana  59405
Sletten Cancer Institute at Benefis HealthcareGreat Falls, Montana  59405
Grant Medical Center Cancer CareColumbus, Ohio  43215
Knox Community HospitalMount Vernon, Ohio  43050
Mount Carmel St. Ann's Cancer CenterWesterville, Ohio  43081
Legacy Good Samaritan Hospital & Comprehensive Cancer CenterPortland, Oregon  97210
Legacy Salmon Creek Medical CenterVancouver, Washington  98686
Rocky Mountain OncologyCasper, Wyoming  82609
Regional Cancer Center at Memorial Medical CenterSpringfield, Illinois  62781-0001
Methodist HospitalHouston, Texas  77030
Queen's Cancer Institute at Queen's Medical CenterHonolulu, Hawaii  96813
Gibbs Regional Cancer Center at Spartanburg Regional Medical CenterSpartanburg, South Carolina  29303
Cancer Centers of the Carolinas - Grove CommonsGreenville, South Carolina  29605
Cancer Centers of the Carolinas - Faris RoadGreenville, South Carolina  29605
Cancer Centers of the Carolinas - Greer Medical OncologyGreer, South Carolina  29650
Cancer Centers of the Carolinas - SenecaSeneca, South Carolina  29672
Cancer Centers of the Carolinas - SpartanburgSpartanburg, South Carolina  29307
Phelps County Regional Medical CenterRolla, Missouri  65401
Cancer Centers of the Carolinas - EastsideGreenville, South Carolina  29601
Mid-Illinois Hematology-Oncology Associates at Community Cancer CenterNormal, Illinois  61761
Rockwood Clinic Cancer Treatment CenterSpokane, Washington  99204-2967
Doctors Medical Center - San Pablo CampusSan Pablo, California  94806
St. Vincent Healthcare Cancer Care ServicesBillings, Montana  59101
Midwest Hematology Oncology Group, IncorporatedSaint Louis, Missouri  63109
Contra Costa Regional Medical CenterMartinez, California  94553-3156
El Camino Hospital Cancer CenterMountain View, California  94040
Kapiolani Medical Center at Pali MomiAiea, Hawaii  96701
Kapiolani Medical Center for Women and ChildrenHonolulu, Hawaii  96826
Straub Clinic and Hospital, IncorporatedHonolulu, Hawaii  96813
OnCare Hawaii, Incorporated - KuakiniHonolulu, Hawaii  96817
OnCare Hawaii, Incorporated - LusitanaHonolulu, Hawaii  96813
Caritas St. Elizabeth's Medical CenterBrighton, Massachusetts  02135-2997
AnMed Cancer CenterAnderson, South Carolina  29621
Lovelace Medical Center - DowntownAlbuquerque, New Mexico  87102
Regional Medical CenterAnniston, Alabama  36202
Cancer Centers of the Carolinas - EasleyEasley, South Carolina  29640
Self Regional Cancer Center at Self Regional Medical CenterGreenwood, South Carolina  29646
Cancer Centers of the Carolinas - Greer Radiation OncologyGreer, South Carolina  29650
Falck Cancer Center at Arnot Ogden Medical CenterElmira, New York  14905
Castle Medical CenterKailua, Hawaii  96734
Kauai Medical ClinicLihue, Hawaii  96766
Central Dupage Cancer CenterWarrenville, Illinois  60555
Clackamas Radiation Oncology CenterClackamas, Oregon  97015
Providence Newberg Medical CenterNewberg, Oregon  97132
Willamette Falls HospitalOregon City, Oregon  97045
Southern Ohio Medical Center Cancer CenterPortsmouth, Ohio  45662
Arizona Cancer Center at University Medical Center NorthTucson, Arizona  85719
Kuakini Medical CenterHonolulu, Hawaii  96817
Mountain States Tumor Institute - MeridianMeridian, Idaho  83642
Mountain States Tumor Institute at St. Luke'sTwin Falls, Idaho  83301
Central Care Cancer Center at Carrie J. Babb Cancer CenterBolivar, Missouri  65613
Carolina Blood and Cancer CareRock Hill, South Carolina  29732
Mercy Clinic Cancer and Hematology - RollaRolla, Missouri  65401
Oncare Hawaii, Incorporated - Pali MomiAiea, Hawaii  96701
Epic Care - OaklandOakland, California  94612
Delnor Hospital - GenevaGeneva, Illinois  60134