Completed

NCT Number: NCT01898312

BRCA1/2 and Effect of Mifepristone on the Breast

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.

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Key information

Conditions

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

Age range

18 year and older

Sex eligibility

Female

Study type

Interventional

Phase

Phase 2

Primary location

Department of Woman and Child Health Karolinska University Hospital

Stockholm, 17176, Sweden

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

includes:

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

Treatment and study plan

Mifepristone

Drug

Randomised controlled trial of Mifepristone and placebo comparator Triobe

Primary outcomes

epithelial cell proliferation in breast tissue

Time frame: 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 outcomes

Vital signs and safety lab analysis

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 3 months

Women with BRCA-1/-2 mutations are followed according to the existing clinical routine with regard to ovarian cancer screening.
Breast symptom evaluation

Time frame: 3months

Breast symptom evaluation will be registered at baseline and during the study by a breast symptom score.

Sponsors and collaborators

Lead sponsor

Karolinska Institutet

Other

Registry information

Official study title

The Effect of a Progesterone Receptor Modulator on Breast Tissue in Women With BRCA-1 and -2 Mutations - a Placebo Controlled RCT.

Important dates

Study start: 2013
Primary completion: 2021
Study completion: 2022
First posted: Jul 12, 2013
Registry last updated: Jan 19, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.