Clinical Trials /

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

NCT01276704

Description:

The investigators will study the effect of 12 months of SDG (Brevail) vs placebo on women at increased risk for development of breast cancer.

Related Conditions:
  • Breast Fibrocystic Change, Proliferative Type
  • Breast Intraductal Proliferative Lesion
  • Breast Lobular Carcinoma In Situ
  • Hereditary Breast and Ovarian Cancer Syndrome
  • Intraductal Proliferative Lesion of the Breast
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Prevention Strategy for Pre-Menopausal Women at High Risk for Development of Breast Cancer
  • Official Title: Flaxseed Lignan as a Prevention Strategy for Pre-Menopausal Women at High Risk for Development of Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: 12377
  • NCT ID: NCT01276704

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
PlaceboPlacebo
secoisolariciresinolSDGflaxseed lignan, SDG

Purpose

The investigators will study the effect of 12 months of SDG (Brevail) vs placebo on women at increased risk for development of breast cancer.

Detailed Description

      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 cell proliferation in pre-menopausal women.
    

Trial Arms

NameTypeDescriptionInterventions
flaxseed lignan, SDGExperimentalSecoisolariciresinol diglycoside
  • secoisolariciresinol
PlaceboPlacebo ComparatorMatched Placebo
  • Placebo

Eligibility 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.

          -  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, acolbifene, 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.
      
Maximum Eligible Age:49 Years
Minimum Eligible Age:21 Years
Eligible Gender:Female
Healthy Volunteers:Accepts Healthy Volunteers

Primary Outcome Measures

Measure: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
Safety Issue:
Description: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

Measure:to determine if 12 months of SDG is associated with favorable modulation of other risk biomarkers
Time Frame:12 months
Safety Issue:
Description:Other biomarkers will be assessed so as to provide explanation for the observed responses.
Measure: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
Safety Issue:
Description:Biomarker modulation will be correlated to blood lignan levels achieved.
Measure:to determine impact or potential impact on quality of life
Time Frame:12 months
Safety Issue:
Description: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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Carol Fabian, MD

Last Updated

January 17, 2018