Breast Cancer BRCA1 Carriers: a Pilot Study

NCT05062174 | Withdrawn DMC FDA Drug

• 1 other identifier: CTO-IUSCCC-0758
• Study Type: observational
• Target: N/A
• Locations: 1 country
• Sites: 2

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).

Conditions

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

Keywords

progesterone signaling; mifepristone; glucocorticoid receptor; androgen receptor

Outcome Measures

Primary Outcomes (1)

• 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)

Study Arms (1)

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; Procedure: Prophylactic mastectomy

Interventions

Mifepristone 200 MG DRUG

Orally, one time dosage of 200 mg

mifepristone + surgery

Prophylactic mastectomy PROCEDURE

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

mifepristone + surgery

Eligibility Criteria

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

Study Population

10 BRCA-1 mutation carriers who plan to undergo prophylactic mastectomy

You may qualify if:

• ≥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
• a. 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Indiana University: lead
• Breast Cancer Research Foundation: collaborator

Study Sites (2)

IU Health Joe and Shelly Schwarz Cancer Center

Carmel, Indiana, 46032, United States

Location

Indiana University Melvin & Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

random core biopsy of breast tissue from one breast at time of biopsy and pre-planned mastectomy, as well as blood samples

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Bulbo-Spinal Atrophy, X-Linked

Interventions

Mifepristone; Prophylactic Mastectomy

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Muscular Atrophy, Spinal; Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Motor Neuron Disease; Neuromuscular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Mastectomy; Surgical Procedures, Operative; Prophylactic Surgical Procedures

Study Officials

• Tarah Ballinger, MD

  Indiana University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CROSSOVER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor Clinical Medicine

Study Record Dates

• First Submitted: September 21, 2021
• First Posted: September 30, 2021
• Study Start: November 1, 2021
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2024
• Last Updated: December 15, 2022

Record last verified: 2022-12

Locations

US (2)