BRCA1/2 and Effect of Mifepristone on the Breast

NCT01898312 | Completed Phase 2

• 1 other identifier: 2012-003703-35
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

Ovarian steroids, as well as their synthetic counterparts gestagens and estrogens have a role in breast cell proliferation and the development of breast cancer. Here, the effect of a progesterone receptor modulator, mifepristone, on cell proliferation in human breast tissue in vivo will be studied in women with BRCA-1 or -2 mutations. Our preliminary results implicate a possible protective effect of mifepristone in breast epithelium. The ability of mifepristone to block breast epithelial cell proliferation may prevent tumorigenesis and may also prove beneficial when used for contraceptive purposes and on other indications. The proposed project concerns a Randomized Controlled Trial on mifepristone versus placebo treatment of women with BRCA-1or -2 mutations with a high risk/incidence of breast cancer and ovarian cancer.

Conditions

Women With Mutations in the Breast Cancer Susceptibility Genes BRCA1,2

Outcome Measures

Primary Outcomes (1)

• epithelial cell proliferation in breast tissue

  Changes from baseline after 12 weeks of mifepristone treatment in epithelial cell proliferation by measuring expression of genes specifically in the pathways involving apoptotic and cell proliferation by microarray study, including PTEN, Bcl-2 and Ki-67 along with steroid receptors.

  3 months

Secondary Outcomes (5)

• Vital signs and safety lab analysis

  3 months

• Side effects and Adverse Events

  3 months

• Endometrial effects

  3 months

• Ovarian effects

  3 months

• Breast symptom evaluation

  3months

Study Arms (2)

Mifepristone

EXPERIMENTAL

treatment with oral mifepristone 50 mg every second day for 12 weeks in 30 women with BRCA 1 or 2 mutation

Drug: Mifepristone

TrioBe

PLACEBO COMPARATOR

treatment with a quarter of a tablet of TrioBe every second day for 12 weeks

Drug: Mifepristone

Interventions

Mifepristone DRUG

Randomised controlled trial of Mifepristone and placebo comparator Triobe

Mifepristone; TrioBe

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pre-menopausal women, \>/= 18 years of age
• with good general health and
• regular menstrual cycles (25-35 days) who are willing and
• able to participate after giving informed consent.
• women having BRCA1/2 mutation and have decided to undergo risk reducing mastectomy

You may not qualify if:

• Any hormonal treatment used within 2 months prior to study start and
• Any contraindication to mifepristone

Sponsors & Collaborators

• Karolinska Institutet: lead

Study Sites (1)

Department of Woman and Child Health Karolinska University Hospital

Stockholm, 17176, Sweden

Location

Related Publications (5)

• Engman M, Skoog L, Soderqvist G, Gemzell-Danielsson K. The effect of mifepristone on breast cell proliferation in premenopausal women evaluated through fine needle aspiration cytology. Hum Reprod. 2008 Sep;23(9):2072-9. doi: 10.1093/humrep/den228. Epub 2008 Jun 24.

  PMID: 18579510 BACKGROUND

• Isern AE, Loman N, Malina J, Olsson H, Ringberg A. Histopathological findings and follow-up after prophylactic mastectomy and immediate breast reconstruction in 100 women from families with hereditary breast cancer. Eur J Surg Oncol. 2008 Oct;34(10):1148-54. doi: 10.1016/j.ejso.2008.03.002. Epub 2008 Apr 23.

  PMID: 18434071 BACKGROUND

• Kauff ND, Brogi E, Scheuer L, Pathak DR, Borgen PI, Hudis CA, Offit K, Robson ME. Epithelial lesions in prophylactic mastectomy specimens from women with BRCA mutations. Cancer. 2003 Apr 1;97(7):1601-8. doi: 10.1002/cncr.11225.

  PMID: 12655515 BACKGROUND

• Poole AJ, Li Y, Kim Y, Lin SC, Lee WH, Lee EY. Prevention of Brca1-mediated mammary tumorigenesis in mice by a progesterone antagonist. Science. 2006 Dec 1;314(5804):1467-70. doi: 10.1126/science.1130471.

  PMID: 17138902 BACKGROUND

• Bartlett TE, Evans I, Jones A, Barrett JE, Haran S, Reisel D, Papaikonomou K, Jones L, Herzog C, Pashayan N, Simoes BM, Clarke RB, Evans DG, Ghezelayagh TS, Ponandai-Srinivasan S, Boggavarapu NR, Lalitkumar PG, Howell SJ, Risques RA, Radestad AF, Dubeau L, Gemzell-Danielsson K, Widschwendter M. Antiprogestins reduce epigenetic field cancerization in breast tissue of young healthy women. Genome Med. 2022 Jun 15;14(1):64. doi: 10.1186/s13073-022-01063-5.

  PMID: 35701800 DERIVED

MeSH Terms

Interventions

Mifepristone

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Kristina Gemzell Danielsson, Professor

  Dept of Womens and Childrens Health Karolinska Institutet

  PRINCIPAL INVESTIGATOR

• Angelique Flöter Rådestad, MD PhD

  Dept of Womens and Childrens Health, Karolinska Institutet

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD Ph.D

Study Record Dates

• First Submitted: July 5, 2013
• First Posted: July 12, 2013
• Study Start: September 1, 2013
• Primary Completion: December 31, 2021
• Study Completion: January 1, 2022
• Last Updated: January 19, 2022

Record last verified: 2022-01

Locations

SE (1)