Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43857   clinical trials with a EudraCT protocol, of which   7284   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2004-000849-38
    Sponsor's Protocol Code Number:CRAD001C2223
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2005-07-05
    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 ConcernedUK - MHRA
    A.2EudraCT number2004-000849-38
    A.3Full title of the trial
    A Phase 3, randomized, double-blind, placebo-controlled multi-center study of RAD001 in combination with letrozole (Femara®) to investigate the value of adding RAD001 to letrozole as a first-line therapy in postmenopausal women with advanced breast cancer
    A.3.2Name or abbreviated title of the trial where available
    N/A
    A.4.1Sponsor's protocol code numberCRAD001C2223
    A.5.1ISRCTN (International Standard Randomised Controlled Trial) NumberN/A
    A.7Trial is part of a Paediatric Investigation Plan Information not present in EudraCT
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorNovartis Pharma Services AG
    B.1.3.4CountrySwitzerland
    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 support
    B.4.2Country
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation
    B.5.2Functional name of contact point
    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 Information not present in EudraCT
    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 nameRAD001
    D.3.2Product code RAD001
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    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 INNEverolimus
    D.3.9.1CAS number 159351-69-6
    D.3.9.2Current sponsor codeRAD001
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    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) Information not present in EudraCT
    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 Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    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 Information not present in EudraCT
    D.3.11.8Extractive medicinal product Information not present in EudraCT
    D.3.11.9Recombinant medicinal product Information not present in EudraCT
    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 Information not present in EudraCT
    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 nameFemara
    D.3.2Product code FEM345
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    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 codeFEM345
    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) Information not present in EudraCT
    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 Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    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 Information not present in EudraCT
    D.3.11.8Extractive medicinal product Information not present in EudraCT
    D.3.11.9Recombinant medicinal product Information not present in EudraCT
    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
    D.8.3Pharmaceutical form of the placeboTablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    The treatment of advanced breast cancer aims at reducing tumor size, slowing progression and metastasis and reducing complications such as fatigue, bone fracture and hypercalcemia. Women with tumors which are hormone dependent are candidates for endocrine therapies which have been shown to effectively delay disease progression and are much less toxic than cytotoxic chemotherapy. This study investigates the benefit of combining the antiendocrine drug letrozole (Femara®) and everolimus (RAD001).
    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 demonstrate superior efficacy of the combination therapy of RAD001 10mg daily plus letrozole 2.5 mg daily versus the combination of placebo plus letrozole 2.5 mg daily in postmenopausal women with metastatic or locally recurrent hormone receptor positive breast cancer based on Progression Free Survival (PFS).
    E.2.2Secondary objectives of the trial
    To focus the demonstration of superior efficacy of the combination therapy on a subpopulation of patients thought to specifically benefit from the combination. This objective is dependent on the identification of a subpopulation having greater benefit from the combination treatment, based on intratumoral molecular characteristics, independently of the data from this study, and prior to the first interim analysis.
    To compare the two treatment arms with regard to the following secondary endpoints: Time To Progression, overall response rate, overall survival, safety
    and
    • to correlate specific molecular characteristics of the tumor with clinical outcome of the therapy
    • to investigate relationships between PK parameters of RAD001 and clinical endpoints, when combined with letrozole.
    • to investigate whether the genetic characteristics inherent to the individual are predictive of response to treatment, susceptibility to adverse events or drug-drug interactions.
    E.2.3Trial contains a sub-study Information not present in EudraCT
    E.3Principal inclusion criteria
    • Adult women (≥ 18 years of age) with metastatic or locally recurrent breast cancer, not amenable to treatment by surgery or radiotherapy
    • Patients whose tumors express at least one hormone receptor (ER or PgR), as confirmed in the central laboratory
    • Patients must be postmenopausal as defined by any of the following criteria:
    1. Radiation induced menopause or surgical bilateral oophorectomy
    2. Women with an intact uterus and
    ≥ 55 years of age or
    < 55 years of age without menses for the last 5 years or
    < 55 years of age and has not had menses for at least the last 12 months (but has had menses in the last 5 years) and has postmenopausal levels of FSH (according to the postmenopausal range of the individual laboratory, and performed at least four weeks after stopping HRT/oral contraceptives)
    3. Women without an intact uterus and
    ≥ 55 years of age or
    < 55 years of age and postmenopausal levels of FSH (according to the postmenopausal range of the individual laboratory, and performed at least four weeks after stopping HRT/oral contraceptives)
    • Patients must have at least one measurable lesion (i.e. a lesion that can be accurately measured in at least one dimension with longest diameter ≥ 20 mm using conventional techniques or ≥10 mm with spiral CT scan (with minimum lesion size no less than double the slice thickness)
    - As the only exception regarding the requirement for at least one measurable lesion, patients with bone metastases as the sole site of disease can be included, provided they have at least 2 lytic bone lesions, detected by either X-Ray, CT scan or MRI.
    • Histological confirmation of breast cancer
    • Tumor tissue (archived or fresh biopsy) must be available prior to randomization for central analysis of:
    - estrogen-receptor (ER) and/or progesterone-receptor (PgR) status
    - molecular markers
    • An additional inclusion criterion, based on specific molecular markers, may be used for patient selection after the interim analysis, in accordance with the adaptive design of the protocol
    • For patients previously treated for metastatic disease there must be objective evidence of progression (according to RECIST) on the previous therapy within no more than three months prior to study entry. Progression must be documented in the patient files, including date and site. Progressive disease is defined as follows:
    - At least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of longest diameter recorded since the treatment started or the appearance of one or more new lesions, OR
    - Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
    • Adequate bone marrow function as shown by: ANC ≥ 1.5 x 109/L, Platelets ≥ 100 x 109/L, Hb >9 g/dL
    • Adequate liver function as shown by: serum bilirubin ≤ 1.5 x ULN, absence of ascites and encephalopathy due to liver disease, INR < 1.7, ALT and AST ≤ 2.5x ULN ( ≤ 5x ULN in patients with liver metastases).
    • Renal function: serum creatinine ≤ 1.5 x ULN
    • Fasting serum cholesterol ≤ 300 mg/dl or 7.75 mmol/L and fasting triglycerides ≤ 2.5 x ULN.
    - In case one or both of these thresholds are exceeded, the patient can only be included after initiation of statin therapy.
    • Performance Status 0-2 on the WHO scale
    • Signed consent to participate in the study must be obtained from patients after they have been fully informed on the nature and potential risks by the investigator with the aid of written information.
    • Life expectancy of at least three months.
    E.4Principal exclusion criteria
    • Inflammatory breast cancer (histologically proven).
    • Patients with only non-measurable lesions other than bone metastasis (e.g. pleural effusion, ascites etc.)
    • Prior systemic endocrine treatment for advanced breast cancer (i.e. metastatic or locally recurrent breast cancer, not amenable to treatment by surgery or radiotherapy). Patients who had bilateral oophorectomy as the only antiendocrine intervention for advanced breast cancer can be included.
    • More than one prior regimen of chemotherapy for advanced breast cancer.
    • patients whose tumor relapsed during or within 12 months from the end of an adjuvant or neo-adjuvant therapy with an AI
    • Any neoadjuvant/adjuvant therapy with tamoxifen alone or in combination with chemotherapy within the past 4 weeks from randomization.
    • CNS metastases, bilateral diffuse lymphangitis carcinomatosa of the lung (>50% of lung involvement), evidence of metastases estimated as more than a third of the liver as defined by sonogram and/or CT scan.
    • Patients in whom localized radiotherapy (for analgesic purposes) is considered an actual requirement (inclusion should be delayed until radiation therapy has been completed and the patient’s condition stabilized).
    • History of other malignancies with exception of:
    - in-situ carcinoma of the cervix or non-melanomatous skin cancer which have received curative therapy
    - cancer treated ≥5 years previously and considered as cured.
    • Patients with a known history of HIV seropositivity.
    • Patients with other concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study (e.g. uncontrolled diabetes, uncontrolled infection, ongoing chronic infection likely to worsen with inhibition of cellular immunity (e.g. chronic viral hepatitis, tuberculosis), uncontrolled hypertension, congestive cardiac failure, ventricular arrhythmias, active ischemic heart disease, myocardial infarction within six months, active bleeding diathesis)
    • Patients with ≥ grade 3 laboratory abnormalities (excluding hyperlipidemia)
    • Known hypersensitivity to everolimus or sirolimus (rapamycin), to letrozole or lactose (contained in formulations of RAD001 and Femara)
    • Patients with a history of noncompliance to medical regimens.
    • Patients unwilling to or unable to comply with the protocol.
    • Patients who received any other investigational drugs within the preceding 30 days.
    • Patients being treated with drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A (Rifabutin, Rifampicin, Clarithromycin, Ketoconazole, Itroconazole, Voriconazole, Ritinavir, Telithromycin) within the last 5 days from randomization
    E.5 End points
    E.5.1Primary end point(s)
    Progression Free Survival
    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 Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Information not present in EudraCT
    E.6.11Pharmacogenomic Yes
    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) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    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 No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    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 Yes
    E.8.2.3Other No
    E.8.3 The trial involves single site in the Member State concerned Information not present in EudraCT
    E.8.4 The trial involves multiple sites in the Member State concerned Information not present in EudraCT
    E.8.5The trial involves multiple Member States Yes
    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 Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    E.8.7Trial has a data monitoring committee Information not present in EudraCT
    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
    N/A
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years4
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero Information not present in EudraCT
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) Information not present in EudraCT
    F.1.1.3Newborns (0-27 days) Information not present in EudraCT
    F.1.1.4Infants and toddlers (28 days-23 months) Information not present in EudraCT
    F.1.1.5Children (2-11years) Information not present in EudraCT
    F.1.1.6Adolescents (12-17 years) Information not present in EudraCT
    F.1.2Adults (18-64 years) Yes
    F.1.3Elderly (>=65 years) Yes
    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 Information not present in EudraCT
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Information not present in EudraCT
    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 state60
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 500
    F.4.2.2In the whole clinical trial 1200
    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)
    N/A
    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 Decision2005-08-03
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2005-08-03
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2011-03-23
    For support, Contact us.
    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.

    European Medicines Agency © 1995-Thu Apr 25 08:03:58 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA