Prevention Strategy for Pre-Menopausal Women at High Risk for Development of Breast Cancer

This study is currently recruiting participants.
Verified December 2013 by University of Kansas
Sponsor:
Collaborator:
Lignan Research, Inc.
Information provided by (Responsible Party):
Carol Fabian, MD, University of Kansas Medical Center Research Institute
ClinicalTrials.gov Identifier:
NCT01276704
First received: January 6, 2011
Last updated: December 23, 2013
Last verified: December 2013
  Purpose

The investigators would like to see if women at increased risk for breast cancer are likely to tolerate SDG daily for 12 months without significant side effects or changes in their menstrual cycles. The investigators would also like to determine if Brevail® can reduce breast cancer pre-menopausal women.


Condition Intervention Phase
Breast Cancer
Drug: Placebo
Drug: secoisolariciresinol
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: Flaxseed Lignan as a Prevention Strategy for Pre-Menopausal Women at High Risk for Development of Breast Cancer

Resource links provided by NLM:


Further study details as provided by University of Kansas:

Primary Outcome Measures:
  • The primary objective is to determine if women randomized to 12 months of SDG exhibit greater change in the proportion of breast epithelial cells expressing benign breast tissue than do women randomized to placebo. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    The primary objective is to determine if women randomized to 12 months of SDG exhibit greater change in the proportion of breast epithelial cells expressing the proliferation marker Ki- 67/MIB-1 in hyperplastic benign breast tissue than do women randomized to placebo.


Secondary Outcome Measures:
  • to determine if 12 months of SDG is associated with favorable modulation of other risk biomarkers [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • to determine if Ki-67 and modulation of other risk biomarkers is correlated with related to change in blood or urine lignans [ Time Frame: 6 months and 12 months ] [ Designated as safety issue: No ]
  • to determine impact or potential impact on quality of life [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    to determine impact or potential impact on quality of life as measured by the BPQ breast pain questionnaire (a modified McGill Pain questionnaire), The Breast Cancer Prevention Trial (BCPT) Symptom Checklist a menstrual diary for cyclicity and cycle length and antimullerian hormone (AMH), a measure of follicular reserve


Estimated Enrollment: 242
Study Start Date: November 2010
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: natural flaxseed lignan, secoisolariciresinol Drug: secoisolariciresinol
1 capsule daily of secoisolariciresinol diglycoside (SDG)50mg
Other Name: natural flaxseed lignan
Placebo Comparator: Placebo Drug: Placebo
The placebo contains same filler materials as commercially available Brevail® but without active SDG.

  Eligibility

Ages Eligible for Study:   21 Years to 49 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

PARTICIPANT SELECTION

  • Risk Level Required for RPFNA Screening for Eligibility

    • Given the low probability of side effects and the desire to be able to generalize results to a moderate as well as high risk population, the target cohort is pre-menopausal women who have a relative risk for breast cancer which is 2-fold or greater than that of the average woman in their age group by virtue of any one of the following conditions:
  • A 1st or 2nd degree relative with breast cancer diagnosed under the age of 60
  • A prior biopsy indicating proliferative breast disease, atypical hyperplasia, or LCIS
  • Multiple prior breast biopsies regardless of histology
  • 50% or higher estimated mammographic density on visual inspection
  • Prior or current RPFNA evidence of atypia
  • Known carrier of a BRCA1 or 2 mutation.

    • Age, Life-Style and Medical Eligibility Criteria for Tissue Screening

Candidates for tissue screening for this study are pre-menopausal women who meet the risk criteria above and all of the following demographic and medical criteria:

  • Age 21 to 49 (limiting the maximum age to 49 will reduce the possibility of reduction in Ki-67 due to entry into menopause transition during the study).
  • Stable hormonal status for the previous 6 months (has not stopped or started oral contraceptives, or experienced lactation or pregnancy) and willing to maintain same status while on study.
  • BMI < 40 kg/m2.
  • Has had at least 4 menstrual cycles in past year
  • If regularly undergoing screening mammography, must have been performed within 9 months prior to baseline RPFNA, and interpreted as not suspicious for breast cancer
  • Breast exam interpreted as normal (not suspicious for cancer).

    • Exclusion Criteria for Screening RPFNA and Study Participation

Candidates are ineligible for tissue screening if they meet any of the following conditions:

  • Consumption of systemic antibiotics during the 3 weeks prior to baseline RPFNA. Systemic antibiotics reduce intestinal bacteria and thus the ability to convert SECO to ENL [104].
  • Consumption of supplements containing SDG (flaxseed or sesame seed) during the 3 weeks prior to baseline RPFNA. ( Consumption of foods containing flaxseed or sesame seed are OK.)
  • Use of any selective estrogen receptor modulator or aromatase inhibitor (tamoxifen, raloxifene, arzoxifene, acolbifine, anastrozole, exemestane, letrozole) within the previous 6 months.
  • Currently enrolled on an interventional investigational study.
  • Bilateral breast implants.
  • Invasive breast cancer or other invasive cancer diagnosis within five years.
  • Metastatic malignancy of any kind.excluding Hodgkin's or non-Hodgkin's lymphoma.
  • Current anticoagulant use.
  • Consumption of coumadin, fish oil, or other anticoagulants during the 3 weeks prior to baseline RPFNA.
  • Any other condition or intercurrent illness that in the opinion of the investigator makes the subject a poor candidate for RPFNA or the trial.

    • Inclusion Criteria for Study Entry
  • RPFNA performed in the follicular portion (day 1-10) of the menstrual cycle. Note that day 1 is defined as the first day of bleeding.
  • RPFNA specimen exhibits hyperplasia +/- atypia (Masood score of ≥13) with ≥500 cells on the cytology slide.
  • Ki-67 ≥2% positivity (≥500 cells).
  • Willing to continue without oral contraceptives throughout the duration of the study participation (12 months). Non-oral contraceptives are permissible. If heterosexually active, must be agreeable to use some non-hormonal form of contraception during the trial or husband or partner must have had a vasectomy. (Safety of SDG during pregnancy has not been documented).
  • Have reasonable organ function as documented by metabolic chemistry profile.
  • Willing to undergo a history and physical at baseline and 12 months and be contacted periodically by the trial coordinator during the 12 month study period.
  • Willing to have blood drawn at baseline and twelve months.
  • Able to understand and willing to provide informed consent for the RPFNA's and study participation.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01276704

Contacts
Contact: Bruce F Kimler, Ph.D. 913-588-4523 bkimler@kumc.edu

Locations
United States, Arkansas
University of Arkansas for Medical Sciences Recruiting
Little Rock, Arkansas, United States, 72205
Contact: Laura Adkins, MAP, CCRP    501-526-6990 ext 8268    LLAdkins@uams.edu   
Principal Investigator: Suzanne Klimberg, MD         
United States, Illinois
Northwestern University Medical Center Recruiting
Chicago, Illinois, United States, 60611
Contact: Pranjal Gholkar    312-472-4763    p-gholkar@northwestern.edu   
Contact: Subhashin Allu    312-472-4759    s-allu@northwestern.edu   
Principal Investigator: Seema A Khan, MD         
United States, Kansas
University of Kansas Medical Center Recruiting
Kansas City, Kansas, United States, 66160
Contact: Jessica Box    913-588-3622    jbox@kumc.edu   
Principal Investigator: Carol Fabian, MD         
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Alexandra Paulo    617-582-7107    alexandra_paulo@dfci.harvard.edu   
Principal Investigator: Judy E Garber, MD         
United States, Oklahoma
University of Oklahoma Health Sciences Center Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: Nancy Cleaver, RN    405-271-8770    nancy-cleaver@ouhsc.edu   
Principal Investigator: William C Dooley, MD         
United States, Washington
University of Washington Recruiting
Seattle, Washington, United States, 98109-1023
Contact: Donielle O'Connor    206-288-2234    doconnor@seattlecca.org   
Principal Investigator: Larissa A Korde, MD MPH         
Sponsors and Collaborators
Carol Fabian, MD
Lignan Research, Inc.
Investigators
Principal Investigator: Carol Fabian, MD University of Kansas
  More Information

No publications provided

Responsible Party: Carol Fabian, MD, Professor, Director Breast Cancer Prevention Unit, University of Kansas Medical Center Research Institute
ClinicalTrials.gov Identifier: NCT01276704     History of Changes
Other Study ID Numbers: 12377
Study First Received: January 6, 2011
Last Updated: December 23, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Secoisolariciresinol
Phytoestrogens
Estrogens, Non-Steroidal
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 22, 2014