Plain English Summary
Trial website
Additional identifiers
EudraCT number
ClinicalTrials.gov number
NCT02408770
Protocol/serial number
19209
Study information
Scientific title
A pilot prevention study of the effects of the anti-progestin Ulipristal acetate (UA) on surrogate markers of breast cancer risk
Acronym
Study hypothesis
1.4 million women worldwide are diagnosed with invasive breast cancer (BC) each year and over a third die from their disease. Uptake and adherence to licensed chemo-preventative agents, tamoxifen and raloxifene, is low due in part to their adverse toxicity profiles. There is an urgent need for effective, well tolerated and safe breast cancer chemo-preventative agents. Endogenous progesterone induces proliferation of the normal mammary stem/progenitor cell population and exogenous progesterone is well known to increases the risk of postmenopausal breast cancer. Taken together these data suggest antagonism of PgR signaling may be a fruitful approach in the prevention of BC. Ulipristal acetate (UA) is a well-tolerated anti-progestin already licensed for the treatment of benign uterine fibroids. This project will, for the first time, determine the effects of the PgR antagonist UA on the normal breast in women at increased risk of BC and correlate molecular with imaging (MRI) effects.
Ethics approval
UK National Research Ethics Service: North West – Greater Manchester South Committee, provisional approval 18/06/2015, ref: 15/NW/0478
Study design
Non-randomised; Interventional; Design type: Prevention
Primary study design
Interventional
Secondary study design
Non randomised study
Trial setting
Hospitals
Trial type
Prevention
Patient information sheet
Not available in web format, please use contact details to request a participant information sheet
Condition
Malignant neoplasm of breast
Intervention
1. Treatment: Ulipristal acetate 5mg daily for 12 weeks
2. Vacuum assisted breast biopsies before and on treatment
3. Imaging, MRI and USS elastography before and on treatment
Intervention type
Drug
Phase
Phase II
Drug names
Ulipristal acetate
Primary outcome measure
The change in the proliferation of normal breast epithelium, assessed by Ki67, from baseline to 3 months on treatment with ulipristal acetate
Secondary outcome measures
1. The changes in expression of individual genes and key pathways induced by UA therapy at baseline and after 3 months of therapy
2. The change in tissue stiffness and collagen organisation induced by UA therapy at baseline and after 3 months of therapy
3. The changes in key stem cell and PgR target proteins induced by UA therapy at baseline and after 3 months of therapy
4. The proportion and type of clonogenic cells in the breast following treatment with UA at baseline and after 3 months of therapy
5. MRI imaging biomarkers of anti-progestin (UA) activity at baseline and after 3 months of therapy
6. The side effect profile of UA in this patient population at baseline and then monthly to 4 months
Overall trial start date
01/01/2014
Overall trial end date
30/09/2017
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Premenopausal females aged between 25 and 45 years
2. Regular menses defined as date of onset of last menstrual period +/ 3 days of expected
3. 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 4050 years
4. Ovulatory menstrual cycles defined as serum progesterone =15nmol 7 days prior to expected onset of menses
5. eGFR = 40mls/min/1.73m2 in view of requirement for gadolinium contrast MRI scans
6. Willing and able to provide informed consent to undergo all trial procedures
Participant type
Healthy volunteer
Age group
Adult
Gender
Both
Target number of participants
Planned Sample Size: 30; UK Sample Size: 30
Participant exclusion criteria
1. Personal history of breast, uterine, cervical or ovarian cancer
2. Breast feeding within the last 3 months
3. Pregnant or planning for pregnancy in the next 6 months. Pregnancy must be excluded with serum ßhCG <5nmol during screening.
4. Known hypersensitivity to radiological contrast media or to ulipristal acetate or any of its excipients (microcrystalline cellulose, mannitol, croscarmellose sodium, talc, magnesium stearate)
5. Current treatment with:
5.1. Antiestrogens (e.g. tamoxifen or raloxifene), GnRH analogue therapy (e.g. goserelin or buserelin) or hormonal contraceptives including androgens such as cyproterone acetate. Such treatments must have been stopped for at least6 months and regular menstrual cycles resumed
5.2. Corticosteroids at any dose, these must have been stopped for at least 1 month with low likelihood that retreatment will be required
5.3. Antiplatelet or anticoagulant therapy – must have been stopped for at least 7 days and clotting be at satisfactory levels
5.4. Moderate or potent inhibitors of CYP3A4
5.5. Potent inducers of CYP3A4
6. APTT and PT outside the normal institutional ranges. Hb <100g/l and platelet count <150x109/l
7. Serum creatinine, bilirubin, ALT, ALP or LDH >1,5xULN
8. Contraindications to MRI, such as intracranial aneurysm clips, implanted electrical devices and intraocular metallic foreign bodies
9. Comorbidity that would put the patient at increased risk such as recognised bleeding diathesis, moderate to severe hepatic impairment, moderate or severe renal impairment (eGFR <40 ml/min/1.73m2), severe asthma not adequately controlled with corticosteroids (note steroid usage precludes trial entry)
10. Prior breast enhancement/augmentation surgery
11. Genital bleeding of unknown aetiology
Recruitment start date
01/09/2015
Recruitment end date
31/08/2016
Locations
Countries of recruitment
United Kingdom
Trial participating centre
University Hospital of South Manchester
Genesis Prevention Centre
Wythenshawe Hospital
Southmoor Road
Manchester
M23 9LT
United Kingdom
Funders
Funder type
Charity
Funder name
Breast Cancer Campaign
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
other non-profit
Location
United Kingdom
Results and Publications
Publication and dissemination plan
To be confirmed at a later date
Intention to publish date
Participant level data
Stored in repository
Basic results (scientific)
Publication list