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    The EU Clinical Trials Register currently displays   35503   clinical trials with a EudraCT protocol, of which   5838   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2014-002001-37
    Sponsor's Protocol Code Number:009684QM
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2015-01-27
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedUK - MHRA
    A.2EudraCT number2014-002001-37
    A.3Full title of the trial
    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.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A window of opportunity study of enzalutamide (alone or in combination with exemestane) in patients with newly diagnosed breast cancer who are awaiting surgery for their cancer.
    A.3.2Name or abbreviated title of the trial where available
    ARB v1.0
    A.4.1Sponsor's protocol code number009684QM
    A.5.4Other Identifiers
    Name:Not applicableNumber:Not applicable
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorQueen Mary University London
    B.1.3.4CountryUnited Kingdom
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing support
    B.4.2Country
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAstellas Pharma Europe Ltd
    B.5.2Functional name of contact pointSuzanne Day
    B.5.3 Address:
    B.5.3.1Street Address2000 Hillswood Drive,
    B.5.3.2Town/ cityChertsey
    B.5.3.3Post codeKT16 0RS
    B.5.3.4CountryUnited Kingdom
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Xtadi
    D.2.1.1.2Name of the Marketing Authorisation holderAstellas Pharma Europe B.V.
    D.2.1.2Country which granted the Marketing AuthorisationNetherlands
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameEnzalutamide
    D.3.2Product code MDV3100
    D.3.4Pharmaceutical form Capsule, soft
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNEnzalutamide
    D.3.9.1CAS number 915087-33-1
    D.3.9.2Current sponsor codeEnzalutamide
    D.3.9.3Other descriptive nameMDV3100, MDV-3100, MDV 3100
    D.3.9.4EV Substance CodeAS1
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number160
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Aromasin
    D.2.1.1.2Name of the Marketing Authorisation holderPfizer Limited
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameExemestane
    D.3.2Product code Not applicable
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNExemestane
    D.3.9.1CAS number 107868-30-4
    D.3.9.2Current sponsor codeExemestane
    D.3.9.3Other descriptive nameN/A
    D.3.9.4EV Substance CodeAS4
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNExemestane
    D.3.9.1CAS number 107868-30-4
    D.3.9.2Current sponsor code107868-30-4
    D.3.9.3Other descriptive nameN/A
    D.3.9.4EV Substance CodeAS5
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Primary breast cancer
    E.1.1.1Medical condition in easily understood language
    Newly diagnosed breast cancer
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 17.1
    E.1.2Level PT
    E.1.2Classification code 10057654
    E.1.2Term Breast cancer female
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    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.
    E.2.2Secondary objectives of the trial
    - 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
    E.2.3Trial contains a sub-study No
    E.3Principal 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 < 1.5 x ULN
    d) Bilirubin level < 1.5 x ULN
    e) Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) <3 x ULN

    Inclusion Criteria unique to the ER+ve cohort
    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:
    a) Age ≥55 years and 1 year or more of amenorrhea
    b) Age <55 years and 1 year or more of amenorrhea with LH and/or FSH levels in the postmenopausal range
    c) Age <55 with prior hysterectomy but intact ovaries with LH and/or FSH levels in the postmenopausal range
    d) Status after bilateral oophorectomy (≥ 28 days prior to first study treatment)

    Inclusion Criteria unique to the AR+ve, TNBC cohort
    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
    a) ER with <1% of cells positive on IHC or an IHC score (Allred) of ≤2
    b) PR with <1% of tumour cells positive on IHC or an Allred score of ≤2
    c) 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.
    E.4Principal 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.
    E.5 End points
    E.5.1Primary 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 (RRδKi67), defined as a ≥50% fall in Ki67 expression over the course of the study treatment.
    E.5.1.1Timepoint(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.
    E.5.2Secondary end point(s)
    1. Secondary Ki67 analyses:
    - Geometric mean change in Ki67 expression at the end of study treatment (Mean ΔKi67) (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 (RRΔKi67), 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 ΔCaspase-3).
    - Individual apoptotic response (RRΔCaspase-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.
    E.5.2.1Timepoint(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 completion of study treatment.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Information not present in EudraCT
    E.8.2.2Placebo Information not present in EudraCT
    E.8.2.3Other Information not present in EudraCT
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned10
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA41
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The end of the trial is defined as 12 months after the last patient visit takes place in both cohorts.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days31
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months1
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1Number of subjects for this age range: 0
    F.1.1.1In Utero No
    F.1.1.1.1Number of subjects for this age range: 0
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.2.1Number of subjects for this age range: 0
    F.1.1.3Newborns (0-27 days) No
    F.1.1.3.1Number of subjects for this age range: 0
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.4.1Number of subjects for this age range: 0
    F.1.1.5Children (2-11years) No
    F.1.1.5.1Number of subjects for this age range: 0
    F.1.1.6Adolescents (12-17 years) No
    F.1.1.6.1Number of subjects for this age range: 0
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 0
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 0
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male No
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state10
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 235
    F.4.2.2In the whole clinical trial 235
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    None, this is a window of opportunity trial. On completion of the study participating patients will either be considered for definitive surgery or primary medical treatment, e.g. neoadjuvant chemotherapy, at the discretion of the treating physician.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2015-02-23
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-03-03
    P. End of Trial
    P.End of Trial StatusOngoing
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