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    Summary
    EudraCT Number:2013-002588-24
    Sponsor's Protocol Code Number:CLEE011A2201
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2013-08-30
    Trial results View 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 ConcernedNetherlands - Competent Authority
    A.2EudraCT number2013-002588-24
    A.3Full title of the trial
    A randomized pre-surgical pharmacodynamics study to assess the biological activity of LEE011 plus letrozole versus single agent letrozole in primary breast cancer
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A pharmacodynamics pre-surgical study of LEE011 in early breast cancer patients
    A.3.2Name or abbreviated title of the trial where available
    MONALEESA-1
    A.4.1Sponsor's protocol code numberCLEE011A2201
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT01919229
    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 SponsorNovartis Pharma AG
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportNovartis Pharma Services AG
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationNovartis Pharma AG
    B.5.2Functional name of contact pointClinical Trial Information Desk
    B.5.3 Address:
    B.5.3.1Street AddressForum 1, Novartis Campus
    B.5.3.2Town/ cityBasel
    B.5.3.3Post code4056
    B.5.3.4CountrySwitzerland
    B.5.4Telephone number+41613241111
    B.5.5Fax number+41613248001
    B.5.6E-mailclinicaltrial.enquiries@novartis.com
    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 No
    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.3.2Product code LEE011
    D.3.4Pharmaceutical form Capsule
    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.3.9.2Current sponsor codeLEE011A2201
    D.3.9.4EV Substance CodeSUB31644
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number200 to 600
    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 Letrozole
    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 nameletrozole
    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 INNLETROZOLE
    D.3.9.1CAS number 112809-51-5
    D.3.9.2Current sponsor codeFEM 345
    D.3.9.4EV Substance CodeSUB08444MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2.5
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    HR+, HER2- early breast cancer
    E.1.1.1Medical condition in easily understood language
    Early Breast Cancer
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To estimate the difference in anti-proliferative activity of LEE011 600 mg
    QD and LEE011 400 mg QD in combination with letrozole from baseline to time of surgery (day15) as determined by cell cycle
    response rate 2.5 mg QD vs
    single agent letrozole 2.5 mg QD as measured by changes in Ki-67 levels
    E.2.2Secondary objectives of the trial
    1. To evaluate the safety and tolerability of the combination of LEE011 +
    letrozole as measured by frequency and severity of AEs, laboratory
    abnormalities.
    To characterize the ECG effects of LEE011
    at 400 mg and 600 mg QD in combination with letrozole
    2. To assess pharmacodynamics markers related to the activity of LEE011 in
    breast cancer as measured by changes between baseline and posttreatment
    expression of markers such as- but not limited to- pRB and
    CDK1
    3.To assess pharmacokinetics of LEE011 (and any relevant metabolites)
    and letrozole as measured by PK parameters, including but not limited to,
    Cmax, Tmax, AUClast for LEE011 (and any relevant metabolites) and
    letrozole.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Female patient is ≥ 18 years old at the time of informed consent, with newly
    diagnosed resectable breast cancer, who received no prior therapy for
    breast cancer.
    2. Patient is postmenopausal. Postmenopausal status is defined either
    by:
    • Prior bilateral oophorectomy
    • Age ≥60
    • Age <60 and amenorrhea for 12 or more months and FSH and
    estradiol in the postmenopausal range.
    3. Patient has a histologically (and/or cytologically) confirmed diagnosis
    of estrogen-receptor positive and/or progesterone receptor positive
    breast cancer by local laboratory.
    4. Patient has a grade II or grade III invasive breast cancer
    5. Patient has HER2 negative breast cancer defined as a negative in situ
    hybridization test or an IHC status of 0, 1+ or 2+ (if IHC 2+, a negative
    in situ hybridization (respectively FISH/CISH/SISH) test is required) by
    local laboratory testing
    6. Patient has at least one breast lesion with a diameter of ≥1.0 cm by
    ultrasound, mammography, CT-scan, or MRI. If more than one imaging
    modality has been performed, then the most accurate imaging modality
    should be used to record the lesion measurements.7. Patient has an Eastern Cooperative Oncology Group (ECOG)
    performance status 0 or 1
    E.4Principal exclusion criteria
    1. Patient has received any prior therapy for breast cancer.
    2. Patient has a concurrent malignancy or malignancy within 3 years of
    randomization, with the exception of adequately treated, basal cell skin cancer,
    squamous cell carcinoma, non-melanomatous skin cancer or
    curatively resected cervical cancer.
    3. Patient has active cardiac disease or a history of cardiac dysfunction
    including any of the following:
    • History of angina pectoris, symptomatic pericarditis, or myocardial
    infarction within 12 months prior to study entry
    • History of documented congestive heart failure (New York Heart
    Association functional classification III-IV)
    • Documented cardiomyopathy
    • Patient has a Left Ventricular Ejection Fraction (LVEF) < 50% as
    determined by Multiple Gated acquisition (MUGA) scan or
    echocardiogram (ECHO)
    • History of ventricular, supraventricular, nodal arrhythmias, or any
    other cardiac arrhythmias, Long QT Syndrome or conduction
    abnormality in the previous 12 months.
    • Family history of QTc prolongation or of unexplainable sudden
    death at <50 years of age.
    • On screening 12 lead ECG, any of the following cardiac
    parameters: bradycardia (heart rate < 50 at rest), tachycardia
    (heart rate > 90 at rest), PR interval > 220 msec, QRS interval
    >109 msec, or QTcF >450 msec.
    • Systolic blood pressure >160 mmHg or <90 mmHg.
    4. Patient is currently receiving any of the following medications (see
    Appendix 1 for details):
    • That are known strong inducers or inhibitors of CYP3A4.
    • That have a narrow therapeutic window and are predominantly
    metabolized through CYP3A4.
    • That have a known risk to prolong the QT interval or induce
    Torsades de Pointes.
    E.5 End points
    E.5.1Primary end point(s)
    Cell cycle response rate defined as the percentage of patients who
    achieve a reduction in Ki67 expression to natural logarithm of
    percentage positive Ki67 of less than 1 at the time of presurgical/surgical biopsy
    E.5.1.1Timepoint(s) of evaluation of this end point
    Difference from baseline to time of surgery in levels of Ki-67
    E.5.2Secondary end point(s)
    1. Frequency and severity of AEs, laboratoryabnormalities
    2. Time matched, placebo corrected, change from baseline
    in QTc and other cardiac intervals, changes in ECG
    morphology, and correlation between the QTc interval
    change from baseline and plasma concentrations of
    LEE011 and/or any relevant metabolites
    3. Changes between baseline and post-treatment
    expression of markers such as- but not limited to- pRb, p-pR and Cyclin D1
    4. PK parameters, including but not limited to, Cmax,
    Tmax, AUClast for LEE011 (and any relevant
    metabolites) and letrozole.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Frequency of AEs
    Day 0 -day 14 i.e Changes from baseline to day of surgery
    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 Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    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) Yes
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial3
    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 concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA7
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Belgium
    France
    Italy
    Netherlands
    Singapore
    Spain
    United States
    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 study is defined as the time point when data collection will stop and the final analysis of the study will occur.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    E.8.9.1In the Member State concerned months10
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial months10
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 30
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 90
    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 state18
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 92
    F.4.2.2In the whole clinical trial 120
    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
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2013-08-30
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2013-12-30
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2014-09-10
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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