Breast Cancer - anti-progestin prevention study 1

ISRCTN	ISRCTN15575894
DOI	https://doi.org/10.1186/ISRCTN15575894
ClinicalTrials.gov number	NCT02408770
Secondary identifying numbers	19209

Submission date: 01/07/2015
Registration date: 01/07/2015
Last edited: 23/10/2018

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-study-of-ulipristal-acetate-to-prevent-breast-cancer-bc-apps1

Contact information

Ms Faiza Idries
Public

Nightingale & Genesis Prevention Centre
Wythenshawe Hospital
Southmoor Road
Wythenshawe
Manchester
M23 9LT
United Kingdom

Phone	0161 291 4408
Email	faiza.idries@mft.nhs.uk

Study information

Study design	Non-randomised; Interventional; Design type: Prevention
Primary study design	Interventional
Secondary study design	Non randomised study
Study setting(s)	Hospital
Study type	Prevention
Participant information sheet	Not available in web format, please use contact details to request a participant information sheet
Scientific title	A pilot prevention study of the effects of the anti-progestin Ulipristal acetate (UA) on surrogate markers of breast cancer risk
Study objectives	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(s)	UK National Research Ethics Service: North West – Greater Manchester South Committee, provisional approval 18/06/2015, ref: 15/NW/0478
Health condition(s) or problem(s) studied	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
Pharmaceutical study type(s)
Phase	Phase II
Drug / device / biological / vaccine name(s)	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 study start date	01/01/2014
Completion date	30/06/2019

Eligibility

Participant type(s)	Healthy volunteer
Age group	Adult
Sex	Both
Target number of participants	Planned Sample Size: 30; UK Sample Size: 30
Key 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
Key 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
Date of first enrolment	01/09/2015
Date of final enrolment	31/08/2016

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

University Hospital of South Manchester

Genesis Prevention Centre
Wythenshawe Hospital
Southmoor Road
Manchester
M23 9LT
United Kingdom

Sponsor information

University Hospital of South Manchester
Hospital/treatment centre

Wythenshawe Hospital, Southmoor Road , Wythenshawe
Manchester
M23 9LT
England
United Kingdom

"ROR"	https://ror.org/00he80998

Funders

Funder type

Charity

Breast Cancer Campaign
Private sector organisation / Other non-profit organizations

Location: United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Stored in repository
Publication and dissemination plan	To be confirmed at a later date
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
HRA research summary			28/06/2023	No	No

Editorial Notes

23/10/2018: The main contact was updated from Donna Watterson to Faiza Idries
22/10/2018: The overall trial end date has been changed from 30/09/2017 to 30/06/2019
02/06/2016: Cancer Help UK lay summary link added.