Primary Breast Cancer ER+vePhase 2ARBNCT02676986
Short-term Preoperative Treatment With Enzalutamide, Alone or in Combination With Exemestane in Primary Breast Cancer
A Phase 2 study testing Enzalutamide and Exemestane in people with Primary Breast Cancer ER+ve and Primary Breast Cancer AR+ve TNBN, run by Queen Mary University of London at 41 sites in 5 countries.
Trial summary
Open-label, international, multicentre window of opportunity phase II trial to evaluate the effects of short-term preoperative therapy with enzalutamide (alone or in combination with exemestane) in women with newly diagnosed invasive primary breast cancer. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Primary Breast Cancer ER+ve, Primary Breast Cancer AR+ve TNBN
- What is being tested?
- Enzalutamide and Exemestane
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 221 participants
- Where
- 41 sitesin 5 countries
- Study dates
- 10 Aug 2015to 31 Dec 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ER+ve tumours defined as ≥1% of tumour cells positive for ER on IHC staining or an IHC score (Allred) of ≥3
- Postmenopausal defined as:
- Age 55 years and 1 year or more of amenorrhea
- Age 55 years and 1 year or more of amenorrhea with LH and/or FSH levels in the postmenopausal range
- Age 55 with prior hysterectomy but intact ovaries with LH and/or FSH levels in the postmenopausal range
- Status after bilateral oophorectomy ( 28 days prior to first study treatment)
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- AR positive tumours defined as any nuclear AR staining by IHC (enrolment may be based on local pathology findings; subsequent review of AR expression by central pathology laboratory will be carried out)
- Triple-negative tumours, i.e. tumour cells are negative for
- ER with <1% of cells positive on IHC or an IHC score (Allred) of ≤2
- PR with <1% of tumour cells positive on IHC or an Allred score of ≤2
- HER2 with 0, 1+ or 2+ intensity on IHC and no evidence of amplification of the HER2 gene on ISH
- Negative serum or urine pregnancy test for women of childbearing potential within 2 weeks prior to the first dose of study treatment, preferably as close to the first dose as possible. Patients of childbearing potential must agree to use adequate contraception (for example, intrauterine device [IUD], birth control pills unless clinically contraindicated, or barrier device) beginning 2 weeks before the first dose of investigational medicinal product (IMP) and for 30 days after the final dose of IMP.
Who cannot join
- Inflammatory breast cancer
- Treatment with any of the following medications within 4 weeks before the baseline diagnostic biopsy is taken:
- Oestrogens, including hormone replacement therapy;
- Androgens (testosterone, dihydroepiandrosterone, etc.);
- 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)
- 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.
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- 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.
- Significant cardiovascular disease, such as
- History of myocardial infarction, acute coronary syndromes or coronary angioplasty/stenting/bypass grafting within the past 6 months.
- 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%;
- History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsade de pointes);
- Hypersensitivity to the active pharmaceutical ingredient or any of the excipients of the IMPs, including Labrasol, butylated hydroxyanisole, and butylated Hydroxytoluene
- 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.
- Psychological, familial, sociological or geographical conditions that do not permit compliance with the study protocol.
- Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational drug within 4 weeks prior to study entry.
Trial locations and contacts
41 sites in 5 countries.
41 sites in 5 countries
Germany28 sites
Evangelisches Krankenhaus Bergisch Gladbachg GmbH Frauenklinik
Bergisch Gladbach, 51465
Charité Campus Mitte
Berlin, 10117
Brustzentrum City St. Gertraudenkrankenhaus
Berlin, 10713
Evangelisches Waldkrankenhaus Spandau
Berlin, 13589
Johanniter Krankenhaus Bonn
Bonn, 53113
Onkologische Schwerpunktpraxis Bremen
Bremen, 28209
Klinikum Chemnitz GmbH
Chemnitz, 09116
Brustzentrum Uniklinik Köln
Cologne, 50931
St. Elisabeth Krankenhaus Köln
Cologne, 50935
Brustzentrum Holweide
Cologne, 51067
Kliniken-Essen-Mitte, Senology
Essen, 45136
Agaplesion Markus Krankenhaus
Frankfurt, 60431
Evangelische Kliniken Gelsenkirchen
Gelsenkirchen, 45879
Hannover Diakovere Henriettenstift
Hannover, 30559
Klinikum Kassel
Kassel, 34125
Klinikum Kempten
Kempten, 87439
UKSH -Campus Kiel
Kiel, 24105
DRK Kliniken Berlin Köpenick
Köpenick, 12559
UKSH Lübeck
Lübeck, 23538
UKSH Lüneburg, Städtisches Krankenhaus
Lüneburg, 21339
Johannes wesling Klinikum (Minden Hospital)
Minden, 32429
Brustzentrum Niederrhein / ÜBAG Prof. Nitz Mönchengladbach
Mönchengladbach, 41061
Onkologisches Zentrum am Rotkreuzklinikum München
München, 80637
Helios-Kliniken Schwerin
Schwerin, 19049
Johanniter Frauenklinik Stendal
Stendal, 39576
Praxisnetzwerk Trosidorf
Troisdorf, D-53840
GRN Klinik Weinheim
Weinheim, 69469
Marienhospital Witten
Witten, 58452
United Kingdom10 sites
Ninewells Hospital and Medical School NHS Tayside
Dundee, DD1 9SY
Royal Devon and Exeter NHS Foundation Trust
Exeter, EX2 5DW
Barts Health NHS Trust
London, EC1M 6BQ
Guy's and St Thomas' NHS Foundation Trust
London, SE19RT
University Hospital of South Manchester
Manchester, M239QZ
North Manchester Hospital, Pennine Acute Hospitals NHS Trust
Manchester, M8 5RB
Churchill Hospital Oxford University Hospitals NHS Trust
Oxford, OX37LI
University Hospital of North Tees
Stockton-on-Tees, TS19 8PE
Royal Surrey County Hospital NHS Foundation Trust
Surrey, GU2 7XX
Royal Cornwall Hospitals NHS Trust
Truro, Cornwall, TR13LJ
About this study
Official title: Phase II Window of Opportunity Study of Short-term Preoperative Treatment With Enzalutamide (Alone or in Combination With Exemestane) in Patients With Primary Breast Cancer
Open-label, international, multicentre window of opportunity phase II trial to evaluate the effects of short-term preoperative therapy with enzalutamide (alone or in combination with exemestane) in women with newly diagnosed invasive primary breast cancer. The study has two cohorts:
- ER+ve breast cancer
- AR+ve, Triple-negative (i.e. ER-negative, PR-negative and HER2-negative) breast cancer
Read more
Study treatment is planned for a minimum of 15 days and a maximum of 29 days unless there is evidence of unacceptable toxicity or the patient requests to be withdrawn from the trial. Thereafter, patients will either be considered for definitive surgery or primary medical treatment (e.g. neoadjuvant chemotherapy) at the discretion of the treating physician.
The effects of enzalutamide (alone or in combination with exemestane) will be assessed on tumour tissue specimens taken at baseline and on the last day of study treatment.
- Being tested
- Enzalutamide, Exemestane
- Keywords
- Primary Breast Cancer, ER, AR, TNBC
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EnzalutamideDrug
Anti-androgen
ExemestaneDrug
Hormonal therapy (Licenced)
| Study group | Role | What they receive |
|---|---|---|
| Cohort I (ER positive cohort) | Active comparator | Approximately 180 patients with ER positive breast cancer will be randomised 2:1 in favour of enzalutamide to receive enzalutamide plus exemestane or exemestane alone. Receives: Drug: Enzalutamide; Drug: Exemestane |
| Cohort II (AR positive, TNBC cohort) | Active comparator | 55 patients with AR positive, TNBC will receive single agent treatment with enzalutamide. Receives: Drug: Enzalutamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine the difference in geometric mean change in Ki67 expression between the two treatment groups of patients in the ER+ Cohort
The geometric mean change will be determined by the change in Ki67 expression in tumour biopsy samples collected at the End of Treatment to those collected at Pre-Treatment
Measured: 24 months
Determine the individual anti-proliferative response (RRΔKi67) for patients in the AR+ TNBC cohort
The anti-proliferative response is defined as a ≥50% fall in Ki67 expression over the course of the study treatment
Measured: 24 months
Secondary outcomes (8)
Determine the geometric mean change in Ki67 expression at the end of study treatment (Mean ΔKi67) for patients in the AR+ TNBC cohort
Measured: 24 months
Determine the geometric mean Ki67 expression at the end of study treatment (Mean Ki67post) for patients in the ER+ cohort
Measured: 24 months
Determine the individual end-of treatment anti-proliferative response (RRKi67-Post) for all patients.
The RRKi67-Post is defined as the natural logarithm of percentage positive Ki67 of less than 1 at the end of study treatment. For patients in the TNBC cohort, the analysis will be limited to patients with pre-treatment Ln (%Ki67) ≥ 1.
Measured: 24 months
Determine the individual anti-proliferative response (RRΔKi67) for patients in the ER+ cohort.
The RRΔKi67 is defined as a ≥50% fall in Ki67 expression over the course of the study treatment
Measured: 24 months
Determine the geometric mean change in Caspase-3 between end of study treatment and pre-treatment tumour samples (Mean ΔCaspase-3).
Measured: 24 months
Determine the individual apoptotic response (RRΔCaspase-3).
RRΔCaspase-3 is defined as a ≥50% increase in Caspase-3 over the course of the study treatment
Measured: 24 months
Establish the safety and tolerability of enzalutamide alone and in combination with exemestane in this population through review of all AEs and SAEs assessed by CTCAE v4.03
Safety and tolerability will be assessed through reviewing:
- 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
Measured: 24 months
Measure the plasma levels of circulating hormones in blood samples collected prior to and at the end of study treatment.
Plasma levels of androstenedione, DHT, estradiol, estrone, estrone sulfate, follicle stimulating hormone, luteinizing hormone, progesterone, sex hormone binding globulin, and total/free testosterone will be measured.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2016 (estimated)
- Study start10 Aug 2015
- Primary completion31 Dec 2016
- Study completion31 Dec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Primary Breast Cancer ER+veStudies of the same condition, open and under way.
- More trials run by Queen Mary University of LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 221 participants (actual)
Sponsor and investigators
- Lead sponsor
- Queen Mary University of London
- Sponsor type
- University, hospital or other
- Collaborators
- Astellas Pharma Inc
- Responsible party
- Sponsor
- Investigators
- Peter Schmid, Principal investigator, Queen Mary University of London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02676986
- Sponsor's protocol ID
- 009684QM
- Other IDs
- 2014-002001-37, 2014
- Acronym
- ARB
- Status last verified
- Jul 2024
- First submitted
- 1 Feb 2016
- Last updated
- 5 Jul 2024
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Window of Opportunity Study of Short-term Preoperative Treatment With Enzalutamide (Alone or in Combination With Exemestane) in Patients With Primary Breast Cancer
- ClinicalTrials.gov ID
- NCT02676986
- Acronym / sponsor ID
- ARB / 009684QM
- Keywords
- Primary Breast Cancer, ER, AR, TNBC
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 221 participants (actual)
- Lead sponsor
- Queen Mary University of LondonUniversity, hospital or other
- Collaborators
- Astellas Pharma Inc
- Study start
- 10 Aug 2015 (actual)
- Primary completion
- 31 Dec 2016 (actual)
- Study completion
- 31 Dec 2016 (actual)
- First posted
- 9 Feb 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Open-label, international, multicentre window of opportunity phase II trial to evaluate the effects of short-term preoperative therapy with enzalutamide (alone or in combination with exemestane) in women with newly diagnosed invasive primary breast cancer. The study has two cohorts:
- ER+ve breast cancer
- AR+ve, Triple-negative (i.e. ER-negative, PR-negative and HER2-negative) breast cancer
Study treatment is planned for a minimum of 15 days and a maximum of 29 days unless there is evidence of unacceptable toxicity or the patient requests to be withdrawn from the trial. Thereafter, patients will either be considered for definitive surgery or primary medical treatment (e.g. neoadjuvant chemotherapy) at the discretion of the treating physician.
The effects of enzalutamide (alone or in combination with exemestane) will be assessed on tumour tissue specimens taken at baseline and on the last day of study treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort I (ER positive cohort) | Active comparator | Drug: Enzalutamide, Drug: ExemestaneApproximately 180 patients with ER positive breast cancer will be randomised 2:1 in favour of enzalutamide to receive enzalutamide plus exemestane or exemestane alone. |
| Cohort II (AR positive, TNBC cohort) | Active comparator | Drug: Enzalutamide55 patients with AR positive, TNBC will receive single agent treatment with enzalutamide. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- ER+ve tumours defined as ≥1% of tumour cells positive for ER on IHC staining or an IHC score (Allred) of ≥3
- Postmenopausal defined as:
- AR positive tumours defined as any nuclear AR staining by IHC (enrolment may be based on local pathology findings; subsequent review of AR expression by central pathology laboratory will be carried out)
- Triple-negative tumours, i.e. tumour cells are negative for
- Negative serum or urine pregnancy test for women of childbearing potential within 2 weeks prior to the first dose of study treatment, preferably as close to the first dose as possible. Patients of childbearing potential must agree to use adequate contraception (for example, intrauterine device [IUD], birth control pills unless clinically contraindicated, or barrier device) beginning 2 weeks before the first dose of investigational medicinal product (IMP) and for 30 days after the final dose of IMP.
Key exclusion criteria (15 listed)
- Inflammatory breast cancer
- Treatment with any of the following medications within 4 weeks before the baseline diagnostic biopsy is taken:
- 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.
- 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.
- Significant cardiovascular disease, such as
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EnzalutamideAnti-androgen | Drug | Cohort I (ER positive cohort), Cohort II (AR positive, TNBC cohort) |
| ExemestaneHormonal therapy (Licenced) | Drug | Cohort I (ER positive cohort) |
Primary outcome
Determine the difference in geometric mean change in Ki67 expression between the two treatment groups of patients in the ER+ Cohort
Time frame: 24 months
The geometric mean change will be determined by the change in Ki67 expression in tumour biopsy samples collected at the End of Treatment to those collected at Pre-Treatment
Determine the individual anti-proliferative response (RRΔKi67) for patients in the AR+ TNBC cohort
Time frame: 24 months
The anti-proliferative response is defined as a ≥50% fall in Ki67 expression over the course of the study treatment
8 secondary outcomes
Determine the geometric mean change in Ki67 expression at the end of study treatment (Mean ΔKi67) for patients in the AR+ TNBC cohort
Time frame: 24 months
Determine the geometric mean Ki67 expression at the end of study treatment (Mean Ki67post) for patients in the ER+ cohort
Time frame: 24 months
Determine the individual end-of treatment anti-proliferative response (RRKi67-Post) for all patients.
Time frame: 24 months
Determine the individual anti-proliferative response (RRΔKi67) for patients in the ER+ cohort.
Time frame: 24 months
Determine the geometric mean change in Caspase-3 between end of study treatment and pre-treatment tumour samples (Mean ΔCaspase-3).
Time frame: 24 months
Determine the individual apoptotic response (RRΔCaspase-3).
Time frame: 24 months
Establish the safety and tolerability of enzalutamide alone and in combination with exemestane in this population through review of all AEs and SAEs assessed by CTCAE v4.03
Time frame: 24 months
Measure the plasma levels of circulating hormones in blood samples collected prior to and at the end of study treatment.
Time frame: 24 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jul 2024.
- Clinical Study ReportLink provided by the sponsor.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter Schmid principal investigator
Queen Mary University of London
41 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Enzalutamide and Exemestane in people with Primary Breast Cancer ER+ve and Primary Breast Cancer AR+ve TNBN, run by Queen Mary University of London at 41 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 41 sites in Germany, United Kingdom, United States, Ireland, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determine the difference in geometric mean change in Ki67 expression between the two treatment groups of patients in the ER+ Cohort (time frame: 24 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jul 2024.