Primary breast cancer MedDRA version: 17.1 Level: PT Classification code 10057654 Term: Breast cancer female System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Xtadi
Product Name: Enzalutamide
Product Code: MDV3100
Pharmaceutical Form: Capsule, soft
INN or Proposed INN: Enzalutamide
CAS Number: 915087-33-1
Current Sponsor code: Enzalutamide
Other
Sponsors
Queen Mary University London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent prior to admission to this study 2. Female, aged =18 years 3. ECOG performance status 0- 2 4. Histologically confirmed invasive primary breast cancer 5. Palpable breast tumour of any size, or tumour with an ultrasound or MRI size of at least 1.0 cm 6. Haematologic and biochemical indices within the ranges shown below at the screening visit a) ANC = 1500 cells/µl b) Platelet count = 100000/µl c) Serum creatinine concentration =65 years) yes F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1. Inflammatory breast cancer 2. Treatment with any of the following medications within 4 weeks before the baseline diagnostic biopsy is taken: a) Oestrogens, including hormone replacement therapy; b) Androgens (testosterone, dihydroepiandrosterone, etc.); c) Any approved or investigational agent that blocks androgen synthesis or targets the AR (e.g., abiraterone acetate, ARN-509, bicalutamide, enzalutamide, ODM-201, TAK-448, TAK-683, TAK-700) 3. Previous systemic or local treatment for the new primary breast cancer currently under investigation (including surgery, radiotherapy, cytotoxic and endocrine treatments); prior treatment for previous breast cancer or other neoplasms is allowed as long as it was completed at least 1 year prior to inclusion into this trial. 4. History of seizure or any condition that may predispose to seizure; history of loss of consciousness or transient ischemic attack within 12 months before day 1. 5. Significant cardiovascular disease, such as a) History of myocardial infarction, acute coronary syndromes or coronary angioplasty/stenting/bypass grafting within the past 6 months. b) Congestive heart failure New York Heart Association (NYHA) Class III or IV or history of congestive heart failure NYHA class III or IV, unless an echocardiogram or multigated acquisition scan performed within 3 months before day 1 reveals a left ventricular ejection fraction = 45%; c) History of clinically significant ventricular arrhythmias (eg, ventricular tachycardia, ventricular fibrillation, torsade de pointes); 6. Hypersensitivity to the active pharmaceutical ingredient or any of the excipients of the IMPs, including Labrasol, butylated hydroxyanisole, and butylated Hydroxytoluene 7. Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the investigator’s opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an IMP, may affect the interpretation of the results, render the patient at high risk from treatment complications or interferes with obtaining informed consent. 8. Psychological, familial, sociological or geographical conditions that do not permit compliance with the study protocol. 9. Concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug =30 days prior to study entry depending on the half-life of the investigational drug and/or guidance issued by the ARB IMP manufacturer. Please contact the ARB Coordinating team for further information.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Determine the ability of enzalutamide, when taken alone or in combination with exemestane, to affect the growth of cancer cells in patients with newly diagnosed breast cancer. ;Secondary Objective: - Determine the effect of enzalutamide, when taken alone or in combination with exemestane, on tumour cell death. - Establish the safety and tolerability of enzalutamide, when taken alone or in combination with exemestane, in this patient population. - Evaluate changes in circulating hormone levels after enzalutamide administration;Primary end point(s): ER positive cohort: The difference in geometric mean change (post treatment - pre treatment) in Ki67 expression between the two treatment arms. AR positive, triple negative breast cancer cohort: Individual anti-proliferative response (RRdKi67), defined as a =50% fall in Ki67 expression over the course of the study treatment. ;Timepoint(s) of evaluation of this end point: The primary endpoint will be evaluated on breast cancer tumour samples collected prior to the start of study treatment and on completion of study treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Secondary Ki67 analyses: - Geometric mean change in Ki67 expression at the end of study treatment (Mean ?Ki67) (TNBC-cohort). - Geometric mean Ki67 expression at the end of study treatment (Mean Ki67post). - Individual end-of treatment anti-proliferative response (RRKi67-Post), defined as the natural logarithm of percentage positive Ki67 of less than 1 at the end of study treatment - Individual anti-proliferative response (RR?Ki67), defined as a =50% fall in Ki67 expression over the course of the study treatment (ER+ve cohort. 2. Changes in Caspase-3 IHC assessment between pre- and post-treatment tumour samples: - Geometric mean change in Caspase-3 between end-of-treatment and pre-treatment tumour samples (Mean ?Caspase-3). - Individual apoptotic response (RR?Caspase-3), defined as a =50% increase in Caspase-3 over the course of the study treatment. 3. Safety: - Incidence of serious adverse events (SAEs) - Incidence of grade 3 and 4 adverse events (AEs) (CTCAE, version 4.03) - Incidence of all AEs of all grades - Clinically significant changes in vital signs and clinical laboratory results during and following study drug administration 4. Plasma levels of estrone, estrodiol, androstenedione, dihydroepiandrosterone, DHT, total/free testosterone, and sex-hormone binding globulin in blood samples taken prior to and after treatment. ;Timepoint(s) of evaluation of this end point: 1. Secondary Ki67 analysis will be carried out on breast cancer tumour samples collected prior to the start of study treatment and on completion of study treatment. 2. Changes in Caspase-3 will be investigated on breast cancer tumour samples collected prior to the start of study treatment and on completion of study treatment. 3. Safety will be evaluated based on adverse events reported on the pre-treatment, post-treatment and safety visits. 4. Circulating hormone levels will be measured on blood samples collected prior to the start of study treatment and on | — |
Countries
Germany, Spain, United Kingdom, United States
Contacts
Public ContactSuzanne Day
Astellas Pharma Europe Ltd
Outcome results
None listed