Breast Cancer - Anti-Progestin Prevention Study 1 (BC-APPS1)

May 2, 2023 updated by: Manchester University NHS Foundation Trust

A Pilot Prevention Study of the Effects of the Anti-progestin Ulipristal Acetate (UA) on Surrogate Markers of Breast Cancer Risk

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

24

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • Manchester, United Kingdom, M204BX
        • University Hospitals of South Manchester

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

25 years to 45 years (Adult)

Accepts Healthy Volunteers

Yes

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: treatment
ulipristal acetate 5mg daily for 3 months
Drug: ulipristal acetate
selective progesterone receptor modulator
Other Names:
  • Esmya

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
change in the proliferation of normal breast epithelium, assessed by Ki67
Time Frame: 3 months
3 months

Secondary Outcome Measures

Outcome Measure
Time Frame
percentage of luminal basal and mixed colonies by adherent and FACS analyses
Time Frame: 3 months
3 months
Change in MRI background parenchymal enhancement assessed by BiRADs scoring
Time Frame: 3 months
3 months
proportion of participants with specific side effects from ulipristal acetate
Time Frame: monthly to 4 months
monthly to 4 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Manchester University NHS Foundation Trust

Collaborators

University of Manchester

Investigators

  • Principal Investigator: Sacha J Howell, MD PhD, University of Manchester

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 22, 2016

Primary Completion (Actual)

March 18, 2019

Study Completion (Actual)

January 25, 2023

Study Registration Dates

First Submitted

March 31, 2015

First Submitted That Met QC Criteria

March 31, 2015

First Posted (Estimate)

April 3, 2015

Study Record Updates

Last Update Posted (Estimate)

May 4, 2023

Last Update Submitted That Met QC Criteria

May 2, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UHSM0315
  • 2016BS001 (Other Identifier: Manchester University NHS Foundation Trust)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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