Breast Cancer - Anti-Progestin Prevention Study 1

NCT ID: NCT02408770

Last Updated: 2023-05-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-22
• Study Completion Date: 2023-01-25

Brief Summary

The primary objective of this study is to determine the effects of the antiprogestin ulipristal acetate (UA) on the epithelial and stromal compartments of the normal breast in women at increased risk of breast cancer (BC) and to relate these effects to quantitative changes on multiparametric magnetic resonance imaging (MRI). The goal is to define predictive imaging biomarkers for subsequent testing in randomised prevention trials of antiprogestins.

Detailed Description

Breast cancer (BC) is the commonest cancer, affecting 1.4 million women per year of whom a third die from the disease. There is an urgent need for new approaches to BC prevention. Progesterone is a hormone that is produced naturally from a woman's ovaries during each menstrual cycle and is often used in hormone replacement therapy (HRT) after the menopause. When used in HRT progesterone increases the risk of BC and BC death. In experiments in mice and rats progesterone has been shown to increase the growth of the normal mammary gland (the rodent breast). When human breast tissue is grown in the laboratory it also grows in response to progesterone. In particular progesterone has been shown to increase the growth of particular cells called stem cells which survive for a long time in the breast. It is thought that the exposure of these stem cells to progesterone over many years is the reason that women whose periods start early and finish late or those who do not have a pregnancy to interrupt their menstrual cycles and those that take HRT all have an increased risk of BC.

In this project the investigators will use a drug that blocks the effects of progesterone called ulipristal acetate (UA, EsmyaTM) that is currently licenced in the treatment of fibroids of the uterus. When used to treat fibroids UA is very well tolerated with no increase in side effects compared to a placebo tablet. 30 women at increased risk of BC will be recruited and have magnetic resonance imaging (MRI) scan and mammogram followed by a biopsy of one breast. After 3 months of UA treatment the MRI will be repeated along with a biopsy from the other breast. The effects of UA on many different cell types in the biopsies, including the stem cells and also the tissues like collagen that support them will be examined in detail. The effects of UA treatment on gene and protein expression in the breast tissue will also be examined. The goal is to identify which women will be sensitive or resistant to UA as a BC prevention treatment. In addition changes in the MRI scans with UA treatment will be examined using several different analysis techniques to try and identify who will likely benefit from UA treatment in the future without the need for biopsies.

Conditions

Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

treatment

ulipristal acetate 5mg daily for 3 months

Group Type: EXPERIMENTAL

ulipristal acetate

Intervention Type: DRUG

selective progesterone receptor modulator

Interventions

ulipristal acetate

selective progesterone receptor modulator

Intervention Type: DRUG

Other Intervention Names

Esmya

Eligibility Criteria

Inclusion Criteria

• Premenopausal females aged between 25 and 45 years
• Regular menses
• Known BRCA1 or BRCA2 mutation or moderate to high risk of developing BC defined as >17% lifetime risk from age 20 or >3% risk between 40-50 years
• Ovulatory menstrual cycles
• eGFR ≥ 40mls/min/1.73m2

Exclusion Criteria

• Personal history of breast, uterine, cervical or ovarian cancer
• Breast feeding within the last 3 months
• Pregnant or planning for pregnancy in the next 6 months.
• Known hypersensitivity to radiological contrast media or to ulipristal acetate or its excipients
• Current treatment with:

Anti-estrogens, GnRH analogues or hormonal contraceptives, corticosteroids or antiplatelet/anticoagulant therapy or moderate or potent inhibitors or inducers of CYP3A4

• APTT and PT outside the normal institutional ranges. Hb <100g/l and platelet count <150x109/l. Serum creatinine, bilirubin, ALT, ALP or LDH >1,5xULN.
• Contraindications to MRI
• Prior breast enhancement/augmentation surgery
• Genital bleeding of unknown aetiology

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

University of Manchester

OTHER

Sponsor Role: collaborator

Manchester University NHS Foundation Trust

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sacha J Howell, MD PhD

Role: PRINCIPAL_INVESTIGATOR

University of Manchester

Locations

University Hospitals of South Manchester

Manchester, , United Kingdom

Countries

United Kingdom

Other Identifiers

2016BS001

Identifier Type: OTHER

Identifier Source: secondary_id

UHSM0315

Identifier Type: -

Identifier Source: org_study_id