Breast Cancer, ER positive, early MedDRA version: 14.1 Level: LLT Classification code 10070577 Term: Oestrogen receptor positive breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Imperial College London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Written informed consent to participate in the trial 2) 18 years of age or older 3) Histologically confirmed ER +ve breast cancer (Allred =3) 4) Any HER2 status 5) Tumour measuring =20mm in longest diameter on ultrasound (US) examination 6)Postmenopausal women as defined by any one of the following criteria: a. Amenorrhoea >12 months at the time of diagnosis and an intact uterus OR, b. prior bilateral oophorectomy OR, c. FSH levels within the postmenopausal range (as per local practice) in women aged =65 years) yes F.1.3.1 Number of subjects for this age range 12
Exclusion criteria
Exclusion criteria: 1) Locally advanced/inoperable breast cancer 2) Clinical evidence of metastatic disease 3) Diffuse or inflammatory tumours 4) Any history of invasive malignancy within 5 years of starting study treatment (other than adequately treated basal cell carcinoma or squamous cell carcinoma of the skin and cervical carcinoma in situ) 5) Evidence of bleeding diathesis and PTT and PT = 1.5 x upper limit of normal 6) Concomitant use (defined as use within 4 weeks prior to entry) of HRT or any other oestrogen-containing medication or supplement (including vaginal oestrogens and phytoestrogens) 7) Previous use of oestrogen implants at ANY time. 8) Concomitant use of: a) Rifampicin and other CYP2C and 3A inducers such as rifabutin, rifapentine, carbamazepine, phenobarbital, phenytoin and St. John’s Wort b) Systemic carbonic anhydrase inhibitors 9) Any of the following cardiac criteria: a) Mean resting corrected QT interval (QTcf) >450 ms obtained from 3 electrocardiograms (ECGs) b) Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g. complete left bundle branch block, third degree heart block c) Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age or any concomitant medication known to prolong the QT interval 10) Uncontrolled abnormalities of serum potassium, sodium, calcium or magnesium levels 11) Evidence of uncontrolled active infection 12) Evidence of significant medical condition or laboratory finding which, in the opinion of the investigator, makes it undesirable for the patient to participate in the trial 13) Subjects unable to lie flat or fit into the scanner 14) Patients on occupational monitoring for radiation exposure
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: This study will use 3’-deoxy-3’-[18F]Fluorothymidine Positron Emission Tomography (FLT-PET) to assess the ability of a novel endocrine treatment for breast cancer, Irosustat, to slow down cancer cell growth.;Secondary Objective: 1) To assess what Irosustat does to the body by measuring blood hormone levels and how much it inhibits its target enzyme activity. 2) To assess safety and tolerability of Irosustat.;Primary end point(s): Changes in FLT uptake as assessed by PET following 2 weeks of treatment with Irosustat.;Timepoint(s) of evaluation of this end point: FLT-PET scans will be performed on day 1 and day 14. Every effort must be made to observe the 14 day time point. However, delays of up to 3 days will be acceptable. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) To characterize the pharmacodynamic profile of Irosustat by measuring peripheral blood steroid hormone levels and assessing the effect of Irosustat on STS inhibition in PBMCs. 2) To evaluate safety and tolerability of Irosustat by collecting toxicities according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v 4.03: June 14, 2010).;Timepoint(s) of evaluation of this end point: While receiving study treatment patients will attend study visits for clinical evaluation and blood sampling at day 1, day 7, day 14 and at 30 days following the last dose of Irosustat. In addition, patients who have consented to the collection of an optional post treatment tumour sample will attend an additional visit as soon as possible following day 14. | — |
Countries
United Kingdom
Contacts
Public ContactDr Ioannis Xynos
Imperial College London
Outcome results
None listed