Breast Cancer BRCA1 Carriers: a Pilot Study

BRCA1 Mutation Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT05062174
• Other study ID #: CTO-IUSCCC-0758
• Status: Withdrawn
• Start date: November 1, 2021
• Est. completion date: December 31, 2024

Study information

• Verified date: December 2022
• Source: Indiana University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. =18 old at the time of informed consent

2. 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.

3. Planning to undergo prophylactic risk reducing mastectomy

4. Premenopausal, defined as:

1. At least one ovary remains in situ, AND

2. Estradiol > 20 or last menstrual period within the prior 3 months

3. Prior hysterectomy is allowed as long as at least one ovary remains in place

5. Must not be pregnant or nursing

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

6. Ability to provide written informed consent and HIPAA authorization

7. 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:

1. 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.

2. Presence of an intrauterine device

3. Personal history of breast or ovarian cancer

4. Active heavy smoker, defined as 10 or more cigarettes per day on any occasion in the past 30 days

5. 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.)

6. 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.

7. History of life- threatening allergic reaction to local anesthesia (lidocaine, xylocaine).

8. Contraindications including but not limited to allergic reactions to mifepristone or other prostaglandins, or inherited porphyrias

9. For the purposes of invasive breast biopsies, women must not be receiving therapeutic anticoagulation or antiplatelet agents

Related Conditions & MeSH terms

• BRCA1 Mutation
• Breast Neoplasms
• High-grade Serous Ovarian Cancer
• TNBC - Triple-Negative Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

Drug:
• Mifepristone 200 MG
Orally, one time dosage of 200 mg

Procedure:
• Prophylactic mastectomy
Planned prophylactic mastectomy (having one or both breasts removed).

Locations

Country	Name	City	State
United States	IU Health Joe and Shelly Schwarz Cancer Center	Carmel	Indiana
United States	Indiana University Melvin & Bren Simon Cancer Center	Indianapolis	Indiana

Sponsors (2)

Lead Sponsor	Collaborator
Indiana University	Breast Cancer Research Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Impact of mifepristone	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.	From baseline (day -2 to day -6) to Breast surgery (day 0)