Short-term Preoperative Treatment With Enzalutamide, Alone or in Combination With Exemestane in Primary Breast Cancer

NCT ID: NCT02676986

Last Updated: 2024-07-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 221 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-08-10
• Study Completion Date: 2016-12-31

Brief 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. 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of 15 days and a maximum of 29 days unless there is evidence of unacceptable toxicity or the patient requests to be withdrawn from the trial.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.

Conditions

Primary Breast Cancer ER+ve; Primary Breast Cancer AR+ve TNBN

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort I (ER positive cohort)

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.

Group Type: ACTIVE_COMPARATOR

Enzalutamide

Intervention Type: DRUG

Anti-androgen

Exemestane

Intervention Type: DRUG

Hormonal therapy (Licenced)

Cohort II (AR positive, TNBC cohort)

55 patients with AR positive, TNBC will receive single agent treatment with enzalutamide.

Group Type: ACTIVE_COMPARATOR

Enzalutamide

Intervention Type: DRUG

Anti-androgen

Interventions

Enzalutamide

Anti-androgen

Intervention Type: DRUG

Exemestane

Hormonal therapy (Licenced)

Intervention Type: DRUG

Eligibility 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

1. ANC 1500 cells/μl

2. Platelet count 100000/μl

3. Serum creatinine concentration < 1.5 x ULN

4. Bilirubin level < 1.5 x ULN

5. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) <3 x ULN

1. ER+ve tumours defined as ≥1% of tumour cells positive for ER on IHC staining or an IHC score (Allred) of ≥3

2. Postmenopausal defined as:

1. Age 55 years and 1 year or more of amenorrhea

2. Age 55 years and 1 year or more of amenorrhea with LH and/or FSH levels in the postmenopausal range

3. Age 55 with prior hysterectomy but intact ovaries with LH and/or FSH levels in the postmenopausal range

4. Status after bilateral oophorectomy ( 28 days prior to first study treatment)

1. 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)

2. Triple-negative tumours, i.e. tumour cells are negative for

1. ER with <1% of cells positive on IHC or an IHC score (Allred) of ≤2

2. PR with <1% of tumour cells positive on IHC or an Allred score of ≤2

3. HER2 with 0, 1+ or 2+ intensity on IHC and no evidence of amplification of the HER2 gene on ISH

3. 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.

Exclusion Criteria

1. Inflammatory breast cancer

2. Treatment with any of the following medications within 4 weeks before the baseline diagnostic biopsy is taken:

1. Oestrogens, including hormone replacement therapy;

2. Androgens (testosterone, dihydroepiandrosterone, etc.);

3. 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

1. History of myocardial infarction, acute coronary syndromes or coronary angioplasty/stenting/bypass grafting within the past 6 months.

2. 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%;

3. History of clinically significant ventricular arrhythmias (e.g., 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. Participation in another clinical trial with any investigational drug within 4 weeks prior to study entry.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Astellas Pharma Inc

INDUSTRY

Sponsor Role: collaborator

Queen Mary University of London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Peter Schmid

Role: PRINCIPAL_INVESTIGATOR

Queen Mary University of London

Locations

MD Anderson Cancer Centre

Houston, Texas, United States

Evangelisches Krankenhaus Bergisch Gladbachg GmbH Frauenklinik

Bergisch Gladbach, , Germany

Charité Campus Mitte

Berlin, , Germany

Brustzentrum City St. Gertraudenkrankenhaus

Berlin, , Germany

Evangelisches Waldkrankenhaus Spandau

Berlin, , Germany

Johanniter Krankenhaus Bonn

Bonn, , Germany

Onkologische Schwerpunktpraxis Bremen

Bremen, , Germany

Klinikum Chemnitz GmbH

Chemnitz, , Germany

Brustzentrum Uniklinik Köln

Cologne, , Germany

St. Elisabeth Krankenhaus Köln

Cologne, , Germany

Brustzentrum Holweide

Cologne, , Germany

Kliniken-Essen-Mitte, Senology

Essen, , Germany

Agaplesion Markus Krankenhaus

Frankfurt, , Germany

Evangelische Kliniken Gelsenkirchen

Gelsenkirchen, , Germany

Hannover Diakovere Henriettenstift

Hannover, , Germany

Klinikum Kassel

Kassel, , Germany

Klinikum Kempten

Kempten, , Germany

UKSH -Campus Kiel

Kiel, , Germany

DRK Kliniken Berlin Köpenick

Köpenick, , Germany

UKSH Lübeck

Lübeck, , Germany

UKSH Lüneburg, Städtisches Krankenhaus

Lüneburg, , Germany

Johannes wesling Klinikum (Minden Hospital)

Minden, , Germany

Brustzentrum Niederrhein / ÜBAG Prof. Nitz Mönchengladbach

Mönchengladbach, , Germany

Onkologisches Zentrum am Rotkreuzklinikum München

München, , Germany

Helios-Kliniken Schwerin

Schwerin, , Germany

Johanniter Frauenklinik Stendal

Stendal, , Germany

Praxisnetzwerk Trosidorf

Troisdorf, , Germany

GRN Klinik Weinheim

Weinheim, , Germany

Marienhospital Witten

Witten, , Germany

Belfast Health and Social Care Trust

Belfast, , Ireland

Vall Hebron Hospital

Barcelona, , Spain

Royal Cornwall Hospitals NHS Trust

Truro, Cornwall, United Kingdom

Ninewells Hospital and Medical School NHS Tayside

Dundee, , United Kingdom

Royal Devon and Exeter NHS Foundation Trust

Exeter, , United Kingdom

Barts Health NHS Trust

London, , United Kingdom

Guy's and St Thomas' NHS Foundation Trust

London, , United Kingdom

University Hospital of South Manchester

Manchester, , United Kingdom

North Manchester Hospital, Pennine Acute Hospitals NHS Trust

Manchester, , United Kingdom

Churchill Hospital Oxford University Hospitals NHS Trust

Oxford, , United Kingdom

University Hospital of North Tees

Stockton-on-Tees, , United Kingdom

Royal Surrey County Hospital NHS Foundation Trust

Surrey, , United Kingdom

Countries

United States; Germany; Ireland; Spain; United Kingdom

Related Links

https://www.clinicaltrialsregister.eu/ctr-search/search?query=2014-002001-37

Clinical Study Report

Other Identifiers

2014-002001-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

009684QM

Identifier Type: -

Identifier Source: org_study_id