Breast Cancer BRCA1 Carriers: a Pilot Study

Sponsor

Indiana University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05062174

Collaborator

Breast Cancer Research Foundation (Other)

Enrollment

Locations

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to examine how a single dose of MIFEPREX® (mifepristone) affects the breast tissue in patients with BRCA1 (a gene that normally acts to restrain the growth of cells in the breast, but if it mutates may lead to breast cancer) mutations undergoing a planned prophylactic mastectomy (having one or both breasts removed).

Condition or Disease	Intervention/Treatment	Phase
BRCA1 Mutation High-grade Serous Ovarian Cancer TNBC - Triple-Negative Breast Cancer	Drug: Mifepristone 200 MG Procedure: Prophylactic mastectomy

Detailed Description

This is a single arm, prospective, observational trial enrolling up to 10 patients within Indiana University Simon Comprehensive Cancer Center. Eligible women will be consented to undergo breast biopsy 2-6 days prior to prophylactic mastectomy and take one dose of mifepristone 2 days prior to prophylactic mastectomy. If the initial biopsy is obtained on Day -2, the mifepristone should be taken AFTER the biopsy. Tissue from the ipsilateral breast will be taken at the time of mastectomy.

Primary Objective To determine the impact of a single 200 mg dose of mifepristone on gene expression and metabolomic alterations in breast tissue of women with BRCA1 mutations who are planning prophylactic mastectomy.

Study Design

Study Type:

Observational

Anticipated Enrollment :

10 participants

Observational Model:

Case-Crossover

Time Perspective:

Prospective

Official Title:

Targeting Progesterone Signaling for Breast Cancer Prevention in BRCA1 Carriers: a Pilot Study

Actual Study Start Date :

Nov 1, 2021

Anticipated Primary Completion Date :

Dec 31, 2023

Anticipated Study Completion Date :

Dec 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
mifepristone + surgery Mifepristone is taken orally as a one-time only dose between 48 and 56 hours before your planned prophylactic mastectomy surgery	Drug: Mifepristone 200 MG Orally, one time dosage of 200 mg Procedure: Prophylactic mastectomy Planned prophylactic mastectomy (having one or both breasts removed).

Arm

Intervention/Treatment

mifepristone + surgery

Mifepristone is taken orally as a one-time only dose between 48 and 56 hours before your planned prophylactic mastectomy surgery

Drug: Mifepristone 200 MG

Orally, one time dosage of 200 mg

Procedure: Prophylactic mastectomy

Planned prophylactic mastectomy (having one or both breasts removed).

Outcome Measures

Primary Outcome Measures

Impact of mifepristone [From baseline (day -2 to day -6) to Breast surgery (day 0)]
To determine the impact of a single 200 mg dose of mifepristone on gene expression and metabolomic alterations in breast tissue of women with BRCA1 mutations.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

≥18 old at the time of informed consent
Known pathogenic germline BRCA1 mutation. The mutation must have been discovered by a CLIA- approved next generation sequencing panel (such as Myriad, Invitae, Ambry, etc) and confirmed by the PI.
Planning to undergo prophylactic risk reducing mastectomy
Premenopausal, defined as:
At least one ovary remains in situ, AND
Estradiol > 20 or last menstrual period within the prior 3 months
Prior hysterectomy is allowed as long as at least one ovary remains in place
Must not be pregnant or nursing

Must have a negative urine pregnancy test for registration and between -6 to day -2 prior to receiving mifepristone

Ability to provide written informed consent and HIPAA authorization
Agrees to pre-treatment core biopsy with donation to the IUSCCC Komen Normal Tissue Bank. Patient will sign a separate informed consent for donation to the IUSCCC Komen Normal Tissue Bank.

Exclusion Criteria:

Patients may not have used progesterone-only contraceptives (i.e. Depo- Provera) within the last 6 months. Combination estrogen/progesterone or estrogen only contraceptives are allowed.
Presence of an intrauterine device
Personal history of breast or ovarian cancer
Active heavy smoker, defined as 10 or more cigarettes per day on any occasion in the past 30 days
Uncontrolled chronic medical condition, including insulin dependent diabetes, NYHA class II, III or IV congestive heart failure, unstable angina, history of myocardial infarction, chronic pulmonary conditions including uncontrolled asthma (symptoms > 2 days/week) or dyspnea requiring oxygen, peripheral vascular disease, symptomatic anemia, uncontrolled psychiatric conditions, chronic kidney disease, or liver disease (cirrhosis, NAFLD, etc.)
Requiring ongoing therapy with strong CYP3A4 inhibitor, steroids, or immunosuppressants (i.e. tacrolimus, cyclosporine, etc.). Please see appendix for full list of excluded co-medications. If questions, please ask the PI.
History of life- threatening allergic reaction to local anesthesia (lidocaine, xylocaine).
Contraindications including but not limited to allergic reactions to mifepristone or other prostaglandins, or inherited porphyrias
For the purposes of invasive breast biopsies, women must not be receiving therapeutic anticoagulation or antiplatelet agents

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	IU Health Joe and Shelly Schwarz Cancer Center	Carmel	Indiana	United States	46032
2	Indiana University Melvin & Bren Simon Cancer Center	Indianapolis	Indiana	United States	46202