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

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ClinicalTrials.gov Identifier: NCT02408770
Recruitment Status : Active, not recruiting
First Posted : April 3, 2015
Last Update Posted : July 16, 2021
Sponsor:
Collaborator:
University of Manchester
Information provided by (Responsible Party):
Manchester University NHS Foundation Trust

Tracking Information
First Submitted Date  ICMJE March 31, 2015
First Posted Date  ICMJE April 3, 2015
Last Update Posted Date July 16, 2021
Actual Study Start Date  ICMJE March 29, 2016
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 31, 2015)
change in the proliferation of normal breast epithelium, assessed by Ki67 [ Time Frame: 3 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 26, 2015)
  • percentage of luminal basal and mixed colonies by adherent and FACS analyses [ Time Frame: 3 months ]
  • Change in MRI background parenchymal enhancement assessed by BiRADs scoring [ Time Frame: 3 months ]
  • proportion of participants with specific side effects from ulipristal acetate [ Time Frame: monthly to 4 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: March 31, 2015)
  • clonogenicity, gene expression, protein expression [ Time Frame: 3 months ]
  • MRI [ Time Frame: 3 months ]
  • side effects [ Time Frame: monthly to 4 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Breast Cancer - Anti-Progestin Prevention Study 1
Official Title  ICMJE A Pilot Prevention Study of the Effects of the Anti-progestin Ulipristal Acetate (UA) on Surrogate Markers of Breast Cancer Risk
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE Breast Cancer
Intervention  ICMJE Drug: ulipristal acetate
selective progesterone receptor modulator
Other Name: Esmya
Study Arms  ICMJE Experimental: treatment
ulipristal acetate 5mg daily for 3 months
Intervention: Drug: ulipristal acetate
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: March 31, 2015)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2021
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 25 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02408770
Other Study ID Numbers  ICMJE UHSM0315
2016BS001 ( Other Identifier: Manchester University NHS Foundation Trust )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Manchester University NHS Foundation Trust
Study Sponsor  ICMJE Manchester University NHS Foundation Trust
Collaborators  ICMJE University of Manchester
Investigators  ICMJE
Principal Investigator: Sacha J Howell, MD PhD University of Manchester
PRS Account Manchester University NHS Foundation Trust
Verification Date July 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP