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    The EU Clinical Trials Register currently displays   43871   clinical trials with a EudraCT protocol, of which   7290   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).

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    Summary
    EudraCT Number:2018-004332-30
    Sponsor's Protocol Code Number:ET18-291
    National Competent Authority:France - ANSM
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2019-07-01
    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 ConcernedFrance - ANSM
    A.2EudraCT number2018-004332-30
    A.3Full title of the trial
    LENVAGIST - A multicentre, comparative, placebo-controlled, double-blinded, phase II study of the efficacy of lenvatinib in patients with locally advanced or metastatic GIST after failure of imatinib and sunitinib
    LENVAGIST – Etude de phase II, multicentrique, comparative, contrôlée contre placebo, en double-insu, de l’efficacité du Lenvatinib chez des patients présentant un GIST localement avancé ou métastatique après échec de l’imatinib et du sunitinib.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study that evaluating the efficacy of lenvatinib in patients with locally advanced GIST after failure of imatinib and sunitinib
    Etude évaluant l’efficacité du Lenvatinib chez des patients présentant un GIST localement avancé après échec de l’imatinib et du sunitinib
    A.3.2Name or abbreviated title of the trial where available
    LENVAGIST
    LENVAGIST
    A.4.1Sponsor's protocol code numberET18-291
    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 SponsorCentre Léon Bérard
    B.1.3.4CountryFrance
    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 supportEISAI SAS
    B.4.2CountryFrance
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationCentre Léon Bérard
    B.5.2Functional name of contact pointJulien
    B.5.3 Address:
    B.5.3.1Street Address28 rue Laennec
    B.5.3.2Town/ cityLYON cedex 08
    B.5.3.3Post code69373
    B.5.3.4CountryFrance
    B.5.4Telephone number+33426 55 68 29
    B.5.5Fax number+33478 78 27 15
    B.5.6E-mailjulien.gautier@lyon.unicancer.fr
    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 Lenvima
    D.2.1.1.2Name of the Marketing Authorisation holderEISAI GmbH
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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 E7080
    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.3.8INN - Proposed INNLenvatinib
    D.3.9.1CAS number 857890-39-2
    D.3.9.3Other descriptive nameLENVATINIB MESILATE
    D.3.9.4EV Substance CodeSUB72971
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    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) Yes
    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
    D.8.3Pharmaceutical form of the placeboCapsule
    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
    Patients with locally advanced or metastatic GIST after failure of imatinib and sunitinib (either on 3rd line treatment or beyond a 3rd line with regorafenib)
    Patients avec un GIST métastatique ou localement avancé, après échec du traitement par imatinib et sunitinib (en 3ème ligne de traitement ou au-delà d’une 3ème ligne par regorafenib)
    E.1.1.1Medical condition in easily understood language
    Patients with metastatic GIST
    Patients présentant un GIST métastatique
    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
    The primary objective is to compare the antitumor efficacy of lenvatinib versus placebo in patients with locally advanced or metastatic GIST after failure of imatinib and sunitinib.
    L’objectif principal est de comparer l’efficacité anti-tumorale du lenvatinib par rapport au placebo chez les patients présentant un GIST localement avancé ou métastatique après échec du traitement par imatinib et sunitinib.
    E.2.2Secondary objectives of the trial
    Secondary objectives of the blinded part of the study are to determine in both arms:
    • The Overall Survival (OS)
    • The Objective Response Rate (ORR)*
    • The Best Overall Response (BOR)*
    • The quality of Life (EORTC QLQ-C30)
    • The tolerance profile
    In patients from the placebo arm who switched into the active treatment group, the following additional objectives will be studied from lenvatinib initiation:
    • The Progression-Free Survival (PFS)*
    • The Objective Response Rate (ORR)*
    • The Best Overall Response (BOR)*
    • The quality of Life (EORTC QLQ-C30)
    • The tolerance profile
    Les objectifs secondaires de la partie de l’étude sont de déterminer dans les deux bras :
    • La survie globale (OS)
    • Le taux de réponse objective (ORR)*
    • La meilleure réponse globale (BOR)*
    • La qualité de vie (EORTC QLQ-C30)
    • Le profil de tolérance
    Pour les patients inclus dans le bras placebo qui ont “switché” vers le traitement actif, les objectifs supplémentaires suivants seront évalués à partir du début du Lenvatinib :
    • La survie sans progression (PFS)*
    • Le taux de réponse objective (ORR)*
    • La meilleure réponse globale (BOR)*
    • La qualité de vie (EORTC QLQ-C30)
    • Le profil de tolérance
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    I1. Male or female ≥ 18 years at the day of consenting to the study
    I2. Patient must have histologically confirmed diagnosis of GIST
    I3. Disease must be locally advanced or metastatic
    I4. Patient who failed (disease progression and/or intolerance) previously at least to imatinib and sunitinib.
    Nota Bene: patients with more than 2 previous anticancer treatments are eligible.
    I5. Patient must have evidence of measurable disease as per the RECIST version 1.1 (Appendix 2)
    I6. Patient must have documented disease progression
    I7. ECOG performance status 0, 1 or 2 (Appendix 3)
    ...See the protocol
    I1. Homme ou femme ≥ 18 ans à la date de signature du consentement éclairé de participation
    I2. Patient avec un diagnostic de GIST confirmé histologiquement
    I3. GIST localement avancé ou métastatique
    I4. Patient en échec (progression ou toxicité) des traitements antérieurs par imatinib et sunitinib
    Nota Bene: Les patients ayant eu plus de 2 traitements anticancéreux sont éligibles.
    I5. Patient avec lésion mesurable selon les RECIST1.1
    I6. Patient présentant une récidive de la maladie documentée
    I7. Indice de performance de l’ECOG ≤2
    ...Voir protocole
    E.4Principal exclusion criteria
    E1. Patient with a documented mutation in PDGFRA exon 18 (D842V substitution).
    E2. Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:
    • Active peptic ulcer disease
    • Known intraluminal metastatic lesions with risk of bleeding
    • Inflammatory bowel disease (e.g. ulcerative colitis, Crohn’s disease), or other gastrointestinal conditions with increased risk of perforation
    • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment
    • Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to:
    • Malabsorption syndrome
    • Major resection of the stomach or small bowel
    E3. Any active/uncontrolled infection, including known infection with HIV, Hepatitis B or Hepatitis C
    E4. Corrected QT interval (QTc) > 480 msecs using Bazett’s formula
    E5. History of any one or more of the following cardiovascular conditions within the past 6 months prior to the first dose of study drug:
    • Cardiac angioplasty or stenting
    • Myocardial infarction
    • Unstable angina
    • Coronary artery bypass graft surgery
    • Symptomatic peripheral vascular disease
    • Class III or IV congestive heart failure, as defined by the New York Heart Association(NYHA) classification
    E6. Poorly controlled arterial hypertension (Systolic blood pressure: 150mmHg / Diastolic blood pressure: 90mmHg).
    Note: Patients with high blood pressure can be enrolled provided that the hypertension is well controlled at a stable dose of antihypertensive therapy for at least 1 week prior to lenvatinib start).
    E7. Prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major).
    ...See the protocol
    E1. Patient présentant une mutation documentée de l’exon 18 PDGFRA (substitution D842V).
    E2. Patient présentant une altération de la fonction GI cliniquement significative pouvant augmenter le risque d’hémorragie GI, incluant mais ne se limitant pas à :
    • Ulcère peptique en cours
    • Lésions métastatiques intraluminales connues avec risque d’hémorragie
    • Maladie intestinale inflammatoire (e.g. colite ulcéreuse, maladie de Crohn), ou autre affection GI susceptible de majorer le risque de perforation.
    • Antécédents de fistule abdominale, perforation GI ou abcès intra-abdominal dans les 28 jours précédant l’initiation du traitement de l’étude.
    • Altération de la fonction gastro-intestinale cliniquement significative pouvant affecter l’absorption du traitement expérimental, incluant mais ne se limitant pas à :
    o Syndrome de malabsorption
    o Résection majeure de l’estomac ou de l’intestin grêle
    E3. Toute infection active ou non contrôlée incluant le VIH, l’hépatite B ou l’hépatite C
    E4. Intervalle QT/QTc > 480 msec selon la formule de Bazett
    E5. Antécédent(s) dans les 6 mois précédant, de l’une ou plusieurs des conditions cardiovasculaires suivantes :
    • Angioplastie ou pose de stent
    • Infarctus du myocarde
    • Angor instable
    • Pontage aorto-coronarien
    • Maladie vasculaire périphérique symptomatique
    • Insuffisance cardiaque de grade III ou IV de la classification de la New York Heart Association (NYHA)
    E6. Hypertension non contrôlée (Pression artérielle systolique : 150mmHg / Pression artérielle diastolique : 90mmHg).
    Note: Les patients ayant une pression artérielle élevée peuvent être inclus si l’hypertension est bien contrôlée avec un traitement antihypertenseur donnée à une dose stable durant au moins 1 semaine avant le début du traitement.
    E7. Chirurgie ou traumatisme majeur dans les 28 jours précédant la première dose de traitement et/ou présence d’une plaie non cicatrisée, fracture ou ulcère (les procédures telles que la mise en place d’un cathéter ne sont pas considérées comme majeures)
    ...Voir protocole
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint will be the Progression-Free Survival (PFS)
    Le critère de jugement principal sera la survie sans progression (PFS)
    E.5.1.1Timepoint(s) of evaluation of this end point
    PFS Assessed locally by the investigational staff, according to the RECISTv1.1.
    PFS évaluée par l’investigateur selon les critères RECISTv1.1.
    E.5.2Secondary end point(s)
    Overall survival is defined as the time from the date of randomisation until the date of death due to any cause.
    Objective Response Rate (ORR) is the proportion of patients with a Complete Response or Partial Response as Best Overall Response.
    Best Overall Response (BOR) is described as the proportion of patients with a best overall response of Complete Response.
    The patient’s Quality of Life will be assessed using the EORTC QLQ-C30.
    The tolerance profile will be described mainly on the frequency of adverse events coded using the common toxicity criteria (NCI-CTC v5.0) grade.
    La survie globale est définie comme le temps écoulé entre la date de la randomisation et la date du décès, quelle qu'en soit la cause.
    Le taux de réponse objective (ORR) est la proportion de patients ayant une réponse complète ou partielle comme meilleure réponse globale.
    La meilleure réponse globale (DB) est décrite comme la proportion de patients ayant une meilleure réponse globale de la réponse complète.
    La qualité de vie du patient sera évaluée à l’aide du test EORTC QLQ-C30.
    Le profil de tolérance sera décrit principalement en fonction de la fréquence des événements indésirables codés à l'aide des critères de toxicité communs (NCI-CTC v5.0).
    E.5.2.1Timepoint(s) of evaluation of this end point
    Tumor assessment at a beginning and throughout the study
    Evaluation de la tumeur tout au début et ce tout au long de l'étude
    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 No
    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 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.8.2.4Number of treatment arms in the trial2
    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 concerned15
    E.8.5The trial involves multiple Member States No
    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 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
    LVLP
    Dernière visite du dernier patient
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned 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: 37
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 37
    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 state74
    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)
    A safety follow-up visit must be performed 30 days after the last study drug administration to ensure that any adverse event has been resolved or returned to the level of presented for inclusion.

    Une visite de suivi de sécurité doit être effectuée 30 jours après la dernière dose d'administration pour s'assurer que tout événement indésirable a été résolu ou qu'il est revenu au niveau de présenter à l'inclusion.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    G.4.1Name of Organisation French Sarcoma Group (GSF-GETO)
    G.4.3.4Network Country France
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2019-07-15
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-04-24
    P. End of Trial
    P.End of Trial StatusOngoing
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