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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02408770
Recruitment Status : Active, not recruiting
First Posted : April 3, 2015
Last Update Posted : January 31, 2023
Sponsor:
Collaborator:
University of Manchester
Information provided by (Responsible Party):
Manchester University NHS Foundation Trust

Study Description
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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.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: ulipristal acetate Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: A Pilot Prevention Study of the Effects of the Anti-progestin Ulipristal Acetate (UA) on Surrogate Markers of Breast Cancer Risk
Actual Study Start Date : March 29, 2016
Estimated Primary Completion Date : March 31, 2023
Estimated Study Completion Date : March 31, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arms and Interventions
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Arm Intervention/treatment
Experimental: treatment
ulipristal acetate 5mg daily for 3 months
 Drug: ulipristal acetate
selective progesterone receptor modulator
Other Name: Esmya


Outcome Measures
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Primary Outcome Measures :
  1. change in the proliferation of normal breast epithelium, assessed by Ki67 [ Time Frame: 3 months ]

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

Eligibility Criteria
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Ages Eligible for Study:   25 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02408770


Locations
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United Kingdom
University Hospitals of South Manchester
Manchester, United Kingdom, M204BX
Sponsors and Collaborators
Manchester University NHS Foundation Trust
University of Manchester
Investigators
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Principal Investigator: Sacha J Howell, MD PhD University of Manchester
More Information
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Responsible Party: Manchester University NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT02408770    
Other Study ID Numbers: UHSM0315
2016BS001 ( Other Identifier: Manchester University NHS Foundation Trust )
First Posted: April 3, 2015    Key Record Dates
Last Update Posted: January 31, 2023
Last Verified: January 2023
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Ulipristal acetate
 Contraceptive Agents, Hormonal
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs
Contraceptive Agents, Female