Breast Cancer - anti-progestin prevention study 1

Recruitment & Eligibility

Status: Completed

Sex: All

Target Recruitment: 30

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

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

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
1. The changes in expression of individual genes and key pathways induced by UA therapy at baseline and after 3 months of therapy<br>2. The change in tissue stiffness and collagen organisation induced by UA therapy at baseline and after 3 months of therapy<br>3. The changes in key stem cell and PgR target proteins induced by UA therapy at baseline and after 3 months of therapy<br>4. The proportion and type of clonogenic cells in the breast following treatment with UA at baseline and after 3 months of therapy<br>5. MRI imaging biomarkers of anti-progestin (UA) activity at baseline and after 3 months of therapy<br>6. The side effect profile of UA in this patient population at baseline and then monthly to 4 months

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