BRCA1/2 and Effect of Mifepristone on the Breast

Phase 2

Completed

• Conditions: Women With Mutations in the Breast Cancer Susceptibility Genes BRCA1,2
• Interventions: Drug: Mifepristone

• Registration Number: NCT01898312
• Lead Sponsor: Karolinska Institutet

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.

Detailed Description

Objectives • Research objective To study the safety and effect of treatment with mifepristone, a progesterone receptor modulator, on epithelial cell proliferation in human breast tissue in women with BRCA-1 or -2 mutations prior to protective mastectomy.

Project description

• Hypothesis/ Theory Mifepristone treatment exerts an antiproliferative, protective effect on breast tissue in women with BRCA-1 or -2 mutations

Study Design Randomized, double blind, placebo controlled trial. Women will be recruited among patients with BRCA-1 or -2 mutations scheduled for prophylactic mastectomy. Included women will be randomized to a 3-month treatment with mifepristone, 50 mg (Mifegyne, Exelgyn, Paris, France) or placebo taken orally every second day. Breast biopsies will be obtained in the luteal phase prior to start of treatment and again during surgery.

Study Timeline

• Study First Submitted: 2013-07-05
• Study First Submitted QC: 2013-07-10
• Study First Posted: 2013-07-12
• Study Start: 2013-09
• Primary Completion: 2021-12-31
• Status Verified: 2022-01
• Study Completion: 2022-01
• Last Update Submitted: 2022-01-15
• Last Update Posted: 2022-01-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 45

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Mifepristone	Mifepristone	treatment with oral mifepristone 50 mg every second day for 12 weeks in 30 women with BRCA 1 or 2 mutation
TrioBe	Mifepristone	treatment with a quarter of a tablet of TrioBe every second day for 12 weeks

Primary Outcome Measures

Name	Time	Method
epithelial cell proliferation in breast tissue	3 months	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.

Secondary Outcome Measures

Name	Time	Method
Breast symptom evaluation	3months	Breast symptom evaluation will be registered at baseline and during the study by a breast symptom score.
Vital signs and safety lab analysis	3 months	Safety data includes vital signs, general- and gynecological-, incl breast - examinations, safety lab (hematology (blood status+CRP), kidney function (Na, K, krea) liver function (ASAT, ALAT, ALP, GT, bilirubin) , thyroid function (TSH,T3,T4), hormonal values FSH ,LH , PRL, SHBG, testosterone, E2 (sensitive) progesterone, urine dipstick and pregnancy test (prior to start). Endometrial histology will be investigated in biopsies obtained at baseline and at surgery. Women with BRCA-1/-2 mutations are followed according to the existing clinical routine with regard to ovarian cancer screening.
Side effects and Adverse Events	3 months	Side effects of mifepristone are mild and the only significant side effect reported in previous clinical trials with the same regimen has been mild flushes. All side effects and SAE/AE as well as any concomitant medication will be recoded by the participating patients in a dairy.
Endometrial effects	3 months	Bleeding patterns and endometrial morphologywill be studied. Endometrial histology and progesterone receptor modulator associated changes will be investigated in biopsies obtained at baseline and at surgery. Bleeding pattern will be registered during the study period by the participating women.
Ovarian effects	3 months	Women with BRCA-1/-2 mutations are followed according to the existing clinical routine with regard to ovarian cancer screening.

Trial Locations

Locations (1)

Department of Woman and Child Health Karolinska University Hospital; 🇸🇪 Stockholm, Sweden