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    The EU Clinical Trials Register currently displays   39192   clinical trials with a EudraCT protocol, of which   6421   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2008-007345-31
    Sponsor's Protocol Code Number:3144A2-3004-WW
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2009-06-30
    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
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    A. Protocol Information
    A.1Member State ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2008-007345-31
    A.3Full title of the trial
    A Randomized Double-blind Placebo-Controlled Trial of Neratinib (HKI-272) After Trastuzumab in Women With Early-Stage HER-2/neu Overexpressed/Amplified Breast Cancer
    A.3.2Name or abbreviated title of the trial where available
    ND
    A.4.1Sponsor's protocol code number3144A2-3004-WW
    A.5.1ISRCTN (International Standard Randomised Controlled Trial) NumberNCT00878709
    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 SponsorWyeth Research, Division of Wyeth Pharmaceuticals, Inc.
    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 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 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.3.1Product nameneratinib
    D.3.2Product code HKI-272
    D.3.4Pharmaceutical form Film-coated 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 INNneratinib
    D.3.9.1CAS number 698387-09-06
    D.3.9.2Current sponsor codeHKI-272
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number40
    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 No
    D.3.11.8Extractive medicinal product No
    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 placeboFilm-coated tablet
    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
    Her2 overexpressed, early stage breast cancer (adjuvant treatmente stage).
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 12.0
    E.1.2Level LLT
    E.1.2Classification code 10006173
    E.1.2Term Breast adenocarcinoma
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of this study is to compare disease free survival (DFS) of women with early stage erbB-2 overexpressed/amplified breast cancer following trastuzumab in the adjuvant setting, receiving neratinib against that of women receiving placebo. DFS is defined as the time from randomization to the first occurrence of the following DFS events: invasive ipsilateral breast tumor recurrence, local/regional invasive recurrence, distant recurrence, death from any cause, and invasive contralateral breast cancer.
    E.2.2Secondary objectives of the trial
    Secondary objectives are to compare additional endpoints of subjects receiving neratinib against those of subjects receiving placebo: o Disease free survival including ductal carcinoma in situ (DFS-DCIS), defined as the time from randomization to the first occurrence of any DFS event or DCIS. o Time to distant recurrence (TTDR), defined as the time between randomization and the date of the first distant recurrence,or death from breast cancer. o Distant disease free survival (DDFS), defined as the time from randomization to the first distant recurrence or death from any cause. o Incidence of central nervous system (CNS) recurrence. o Overall survival (OS). o Short- and long-term safety (including incidence of grade 3 or higher diarrhea).
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    FARMACOGENETICA: Versione:Originale Data:2009/04/29 Titolo:N.A. Obiettivi:Dopo aver raccolto un consenso informato separato, il campione bioptico tumorale originale sara` studiato per: EGFR, amplificazione di erbB-2, erbB-3, ed erbB-4, mutazioni di PIK3CA nei punti caldi (ie, exoni 9,20 mediante sequenziamento genico), amplificazione di PIK3CA (q-PCR o FISH), perdita di PTEN, amplificazione di c-Myc (q-PCR o FISH). Quando la ricaduta della malattia sara` stata documentata patologicamente, saranno richiesti campioni prelevati dalle sedi di ricaduta per le analisi dei biomarker. Il campione bioptico in paraffina fissato in formalina (tumore originale e/o recidiva) potra` essere inviato per le analisi (blocco o serie di sezioni da 5 �m su un numero totale di 14 vetrini per microscopio).

    E.3Principal inclusion criteria
    1.Subjects must have histologically confirmed primary adenocarcinoma of the breast that is erbB-2 positive by one of the following assays, performed locally: o Fluorescence in situ hybridization (FISH) or silver in situ hybridization (SISH) must show gene amplification (defined as >2.2), OR o Chromogenic in situ hybridization (CISH) show gene amplification according to the manufacturer`s kit instructions, OR o Immunohistochemistry (IHC) assay must show strong positive (ie, 3+ = >30% of invasive tumor cells) staining score. 2. Primary tumor ER/PgR status must be known before study entry. 3. Subjects must have completed a course of prior adjuvant trastuzumab. If less than 12 months of trastuzumab have been given, at least 8 prior doses of weekly trastuzumab, or at least 3 prior doses of trastuzumab given every 3 weeks, must have been administered and it must be specified that the subject is either not eligible or unable to receive further adjuvant trastuzumab. The last dose of trastuzumab must have been given >2 weeks and <2 years from randomization. 4. Have a diagnosis of stage 1 through stage 3c primary breast cancer according to the American Joint Committee on Cancer (sixth edition) staging criteria for breast cancer and meet one of the following criteria: o Axillary node-positive disease OR node-negative disease with a primary tumor greater than or equal to 1.0 cm in greatest diameter. (For clarification, isolated tumor cells are considered pN0 and micrometastases are considered pN1.) o Node-negative disease is defined as negative sentinel node biopsy OR no positive lymph nodes found among 6 ancillary nodes examined on axillary node dissection OR status after axillary radiotherapy for sterilization if clinically evaluated as cN0. 5. Adequately treated primary breast cancer with surgery, as defined by prior mastectomy OR lumpectomy, with margins clear of invasive carcinoma and DCIS. Subjects with positive sentinel node biopsies must have subsequent axillary dissection to be eligible; negative sentinel node biopsies require no more axillary surgery for eligibility. 6. Completed treatment with a neoadjuvant or adjuvant chemotherapy regimen containing either an anthracycline or a taxane or any cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) regimen. 7. Clinical and radiologic assessments that are negative for local or regional recurrence of disease or metastatic disease at the time of study entry, including: o Bone scan; required only if alkaline phosphatase (ALP) is &amp;#8805;2 x upper limit of normal (ULN) and/or there are symptoms of metastatic bone disease. A confirmatory imaging study is required if the results from the bone scan are questionable. o Computed tomography (CT) or ultrasound scan of the abdomen; required only if aspartate transaminase (AST)/alanine transaminase (ALT) or ALP is &amp;#8805;2 x ULN, unless the elevation is in the bone fraction. o Chest radiograph. 8. Negative bilateral mammogram (or unilateral mammogram of the remaining breast if unilateral total mastectomy was performed) within 12 months before study entry. Mammogram not indicated in case of bilateral total mastectomy. 9. Subjects with bilateral breast cancers are eligible only if their primary cancers occurred synchronously (ie, diagnosed at the same time [occurring within 6 months of each other]). One or both tumors need to be erbB-2 positive. One could be negative. 10. Female subjects aged 18 years or older. 11. Subjects must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1. 12. Adequate organ function as defined by: o Absolute neutrophil count (ANC): &amp;#8805;1.5 � 109/L (1500/mm3) o Platelet count: &amp;#8805;100 � 109/L (100,000/mm3) o Hemoglobin: &amp;#8805;9.0 g/dL (90 g/L) o Serum creatinine: &amp;#8804;1.5 x ULN o Total bilirubin: &amp;#8804;1.5 � ULN (in case of known Gilbert�s syndrome, <2 x ULN is allowed) o AST and ALT: ...
    E.4Principal exclusion criteria
    1. Clinical or radiologic evidence of local or regional recurrence of disease or metastatic disease at the time of study entry. 2. Currently receiving chemotherapy, radiation therapy, immunotherapy, or biotherapy for breast cancer. 3. Any prior mediastinal irradiation except internal mammary node irradiation for the present breast cancer. 4. Metachronous invasive or DCIS breast cancer (ie, primary breast cancers diagnosed at different times [diagnosed greater than 6 months apart from each other]). 5. Prior therapy with an erbB-1 and/or erbB-2 inhibitor other than trastuzumab. 6. Received any investigational agent within 14 days or 5 half-lives, whichever is longer, before administration of the first dose of investigational product. 7. Pregnant or breastfeeding women. 8. Subjects with a concurrently active second malignancy, other than adequately treated nonmelanoma skin cancers, in situ melanoma, or in situ cervical cancer. Subjects with other nonmammary malignancies must have been disease free for at least 5 years. 9. Subjects with unstable angina, congestive heart failure (New York Heart Association class II, III, or IV) (including individuals who currently use digitalis, beta-blockers, or calcium channel blockers specifically for congestive heart failure), ventricular arrhythmia requiring medical therapy, or with a history of myocardial infarction within 12 months. 10. Subjects with active unresolved infections. 11. Inability or unwillingness to swallow tablets. 12. Significant chronic gastrointestinal disorder with diarrhea as a major symptom (eg, Crohn�s disease, ulcerative colitis, malabsorption, or grade &amp;#8805;2 diarrhea of any etiology at baseline). 13. QTc interval >0.45 seconds or known history of QTc prolongation or torsades de pointes. 14. History of idiopathic ventricular tachycardia or ventricular fibrillation. 15. Subjects with a psychiatric illness that would prevent them from understanding the nature of the investigational therapy and complying with protocol requirements. 16. Any major concurrent illness or medical condition that, in the investigator�s judgment, will substantially increase the risk associated with the subject�s participation in and completion of the study. 17. Known or suspected allergy to neratinib or other compounds related to these classes of medication.
    E.5 End points
    E.5.1Primary end point(s)
    Disease Free Survival (DFS): Time from randomization to the first occurrence of the following DFS events: invasive ipsilateral breast tumor recurrence, local/regional invasive recurrence, distant recurrence, death from any cause, and invasive contralateral breast cancer. For any subject for whom a DFS event has not been observed by the cutoff date of an analysis, DFS will be censored at the date of the last physical examination (including targeted physical examination), either scheduled or unscheduled.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis Yes
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic Yes
    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 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) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    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 concerned40
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA280
    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 Yes
    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
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years7
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years7
    E.8.9.2In all countries concerned by the trial months0
    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.1.3Elderly (>=65 years) Yes
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    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 state600
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 1900
    F.4.2.2In the whole clinical trial 3850
    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 Decision2009-10-30
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2009-06-23
    P. End of Trial
    P.End of Trial StatusOngoing
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