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    Summary
    EudraCT Number:2019-001013-16
    Sponsor's Protocol Code Number:PRODIGE69
    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:2020-05-25
    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 number2019-001013-16
    A.3Full title of the trial
    FOLFIRINOX VERSUS PLATINUM - ETOPOSIDE AS FIRST LINE CHEMOTHERAPY FOR METASTATIC GRADE 3 POORLY DIFFERENTIATED NEUROENDOCRINE CARCINOMA OF GASTRO ENTERO PANCREATIC AND UNKNOWN PRIMARY ASSOCIATED WITH MOLECULAR PROFILING FOR THERAPEUTIC TARGETS & PREDICTIVE BIOMARKERS IDENTIFICATION

    A multi-centre, randomized, comparative phase II study
    FOLFIRINOX VERSUS PLATINE - ÉTOPOSIDE EN PREMIÈRE LIGNE DE TRAITEMENT DES CARCINOMES NEUROENDOCRINES PEU DIFFERENCIÉS DE GRADE 3 MÉTASTATIQUES GASTRO-ENTERO-PANCRÉATIQUE ET DE PRIMITIF INCONNU ASSOCIÉ A L’ÉTABLISSEMENT D’UN PROFIL MOLÉCULAIRE.
    Étude de phase II multicentrique, randomisée et comparative
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    FIRST LINE CHEMOTHERAPY FOR METASTATIC NEUROENDOCRINE CARCINOMA OF GASTRO ENTERO PANCREATIC
    PREMIÈRE LIGNE DE TRAITEMENT DES CARCINOMES NEUROENDOCRINES MÉTASTATIQUES GASTRO-ENTERO-PANCRÉATIQUE
    A.3.2Name or abbreviated title of the trial where available
    FOLFIRINEC
    FOLFIRINEC
    A.4.1Sponsor's protocol code numberPRODIGE69
    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 SponsorCHU DIJON
    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 supportINCa (PHRC K)
    B.4.2CountryFrance
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationfédération francophone de cancérologie digestive
    B.5.2Functional name of contact pointLila GABA
    B.5.3 Address:
    B.5.3.1Street AddressFACULTE DE MEDECINE 7 BD JEANNE D ARC BP87900
    B.5.3.2Town/ cityDIJON CEDX
    B.5.3.3Post code21079
    B.5.3.4CountryFrance
    B.5.4Telephone number+33380393483
    B.5.5Fax number+33380381841
    B.5.6E-maillila.gaba@u-bourgogne.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 FLUOROURACILE TEVA
    D.2.1.1.2Name of the Marketing Authorisation holderTEVA SANTE
    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 nameFLUOROURACILE TEVA
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNFLUOROURACIL SODIUM
    D.3.9.2Current sponsor codefluorouracil
    D.3.9.4EV Substance CodeSUB02225MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/m2 milligram(s)/square meter
    D.3.10.2Concentration typeequal
    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 No
    D.2.1.1.1Trade name CISPLATINE
    D.2.1.2Country which granted the Marketing AuthorisationFrance
    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.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCISPLATIN
    D.3.9.4EV Substance CodeSUB07483MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/m2 milligram(s)/square meter
    D.3.10.2Concentration typeequal
    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: 3
    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 CAMPTO
    D.2.1.2Country which granted the Marketing AuthorisationFrance
    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.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNIRINOTECAN
    D.3.9.1CAS number 97682-44-5
    D.3.9.4EV Substance CodeSUB08295MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/m2 milligram(s)/square meter
    D.3.10.2Concentration typeequal
    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: 4
    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 ELOXATINE
    D.2.1.2Country which granted the Marketing AuthorisationFrance
    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.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNOXALIPLATIN
    D.3.9.1CAS number 61825-94-3
    D.3.9.4EV Substance CodeSUB09490MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/m2 milligram(s)/square meter
    D.3.10.2Concentration typeequal
    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) Yes
    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: 5
    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 ETOPOSIDE TEVA
    D.2.1.2Country which granted the Marketing AuthorisationFrance
    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.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.3Other descriptive nameETOPOSIDE
    D.3.9.4EV Substance CodeSUB07337MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/m2 milligram(s)/square meter
    D.3.10.2Concentration typeequal
    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
    METASTATIC GRADE 3 POORLY DIFFERENTIATED NEUROENDOCRINE CARCINOMA OF GASTRO ENTERO PANCREATIC AND UNKNOWN PRIMARY
    Carcinome neuroendocrine peu différencié de grade 3 ou MINEN avec composante de carcinome neuroendocrine peu différencié de grade 3 Primitif d’origine gastro-entero-pancréatique ou inconnue
    E.1.1.1Medical condition in easily understood language
    METASTATIC NEUROENDOCRINE CARCINOMA
    Carcinome neuroendocrine 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
    To compare the progression-free survival (PFS) with mFOLFIRINOX regimen versus platinum - etoposide regimen according to the investigator using RECIST v1.1 criteria.
    Comparer la survie sans progression (SSP) entre mFOLFIRINOX et platine – étoposide évaluée par l’investigateur selon les critères RECIST 1.1.
    E.2.2Secondary objectives of the trial
    PFS according to the centralized review (RECIST v1.1 criteria)
    Best objective response rate (ORR)
    Median overall survival (OS)
    Safety according to NCI CTC V4.0
    Dose-reductions
    Quality of life assessed by EORTC QLQ-C30 and EQ-5D-5L
    To establish a molecular profile within 2 months after tumor sample submission for each patient enrolled in the study and to provide a molecular tumor board report to the treating physician.
    Frequency of Rb loss in G3 NEC irrespective of the SC or LC subtype
    Correlation of ORR, PFS and OS under both chemotherapy regimens with molecular alterations (Rb, TP53, MSH2…)
    SSP selon la relecture centralisée (critères RECIST v1.1)
    Taux de réponse objective (TRO)
    Survie globale (SG)
    Evènements indésirables selon le NCI CTC V4.0
    Dose intensité - réductions de dose
    Qualité de vie évaluée par les questionnaires EORTC, QLQ-C30 et EQ-5D-5L
    Etablir un profil moléculaire dans les 2 mois après l’envoi de l’échantillon de la tumeur pour chaque patient inclus dans l’étude et fournir un compte-rendu de RCP moléculaire à l’investigateur prenant en charge le patient.
    Pourcentage de perte d’expression de Rb (indépendamment du sous-groupe petites cellules ou grandes cellules)
    Corrélation entre TRO, SSP et SG et les altérations moléculaires (Rb, TP53, MSH2…) dans les deux bras de traitement
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    FOLFIRINEC study is coupled with the establishment of a molecular profile by next generation sequencing (NGS) and immunohistochemistry, which will be discussed in a dedicated molecular tumor board. The molecular report will be sent to the investigator, during the trial, within 2 months after tumor sample submission. This molecular profile will also be used to explore for predictive biomarkers of response to chemotherapy.
    Blood samples will be collected for ctDNA analysis.
    L’étude FOLFIRINEC est couplée à la réalisation d’un profil moléculaire de chaque tumeur par NGS, et immunohistochimie. Ce profil moléculaire fera l’objet d’une discussion en RCP moléculaire. Le compte-rendu de RCP moléculaire sera envoyé à l’investigateur durant l’essai clinique environ deux mois après réception du bloc tumoral. Ce profil moléculaire permettra aussi d’explorer les biomarqueurs de réponse à la chimiothérapie. Des échantillons sanguins seront également collectés pour l’analyse de l’AND tumoral circulant
    E.3Principal inclusion criteria
    •Grade 3 neuroendocrine carcinoma or high grade MiNEN with a grade 3 poorly differentiated neuroendocrine carcinoma component ≥30% of gastro-entero-pancreatic or unknown primary
    •Poorly differentiated
    •Small cell or large cell or non-small cell or non- typeable
    •Metastatic disease
    •First-line, no prior therapy for metastatic disease, no prior use of carboplatin, oxaliplatin, cisplatin, etoposide, irinotecan and 5-fluorouracile
    •At least one measurable lesion as assessed by CT-scan or MRI according to RECIST 1.1 guidelines
    •Available tumor block
    •ANC ≥ 1.5x109/l, platelet ≥ 100x109/l and haemoglobin > 8 g/dl
    •Total bilirubin ≤ 1.5N, AST ≤ 2.5N, ALT≤ 2.5N or AST/ALT ≤ 5N in case of liver metastass.
    •Age ≥ 18 years
    •ECOG Performance Status ≤ 1
    •Signed and dated informed consent, and willing and able to comply with protocol requirements.
    •Women of childbearing potential, as well as men (who have sexual relations with women of childbearing potential) must agree to use an effective method of contraception throughout this study and during the 6 months following administration of the last dose of the study medicinal product
    •Patient who is a beneficiary of the Social security system
    •Carcinome neuroendocrine peu différencié de grade 3 ou MINEN avec composante de carcinome neuroendocrine peu différencié de grade 3 représentant ≥ 30% de la tumeur
    •Tumeur primitive d’origine gastro-entéro-pancréatique ou inconnue
    •À petites cellules ou à grande cellules ou non à petites cellules ou non typable
    •Maladie métastatique
    •1ère ligne de traitement pour une maladie métastatique. Pas de chimiothérapie ou de traitement systémique à visée antitumorale préalable
    •Au moins une lésion mesurable selon les critères RECIST 1.1 évaluée par scanner ou IRM
    •Bloc tumoral disponible
    •PNN≥ 1.5x109/l, plaquettes≥ 100x109/l and hémoglobine > 8 g/dl
    •Bilirubine totale ≤ 1.5N, ASAT ≤ 2.5N, ALAT≤ 2.5N or ASAT/ALAT ≤ 5N en cas de métastases hépatiques
    •Age ≥ 18 ans
    •Status de performance ECOG ≤ 1
    •Patient en capacité de comprendre les modalités de l’essai thérapeutique, de signer le consentement éclairé et de se conformer aux exigences du protocole
    •Les femmes en âge de procréer ainsi que les hommes (ayant des rapports sexuels avec des femmes en âge de procréer) doivent s’engager à utiliser des moyens de contraception efficaces tout au long de l’étude et au cours des 6 mois suivant l’administration de la dernière dose du médicament à l’étude
    •Patient affilié à la sécurité sociale
    E.4Principal exclusion criteria
    •Grade 3 well differentiated neuroendocrine tumor according to WHO 2017 classification
    •Severe renal impairment (creatinine clearance less than 30 mL/min, MDRD)
    •Partial or complete Dihydropyrimidine Dehydrogenase (DPD) deficiency (uracilemia ≥ 16 ng/mL)
    •Gilbert’s syndrome
    •Pre-existing permanent neuropathy (NCI CTC V4.0 grade ≥2)
    •Previously treated by chemotherapy or targeted therapy
    •Brain metastases unless they are asymptomatic or under stable corticosteroid doses for 2 weeks otherwise. Radiation therapy prior to inclusion is required if symptomatic.
    •Combination with sorivudine and others analogues as brivudine (irreversibly inhibits the enzyme dihydropyrimidine dehydrogenase)
    •Treatment with St John’s Wort (Hypericum perforatum)
    •Pregnant women or breastfeeding mother
    •Known or historical active infection with HIV, or known active infection untreated with hepatitis B or hepatitis C
    •History of prior malignancy, except for cured non-melanoma skin cancer, cured in situ cervical carcinoma, or other treated malignancies with no evidence of disease for at least three years.
    •Active or suspected acute or chronic uncontrolled disease that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration, or which, in the judgment of the investigator, would make the patient inappropriate for entry into this study
    •vaccinations (live vaccine) within 30 days prior to start of study drugs
    •Patient under guardianship and/or deprived of his/her freedom
    •QT/QTc interval > 450 msec for male and > 470 msec for female at EKC.
    •K+ < LLN, Mg²+ < LLN, Ca²+ < LLN
    •History or know hypersensitivity to any of the study chemotherapy agents, or their excipients
    •Tumeur neuroendocrine de grade 3 bien différenciée selon la classification OMS 2017
    •Insuffisance hépatiques sévère (clairance de la creatinine inférieure à 30mL/min, MDRD)
    •Deficit partiel ou complete en Dihydropyrimidine Dehydrogenase (DPD) (uracilémie ≥ 16 ng/mL)
    •Maladie de Gilbert
    •Neuropathie préexistante permanent (NCI CTC V4.0 grade ≥2)
    •Précédemment traité par chimiothérapie ou thérapie ciblée
    •Métastases cérébrales sauf si elles sont asymptomatiques ou stables sous corticothérapie pendant deux semaines. La radiothérapie est nécessaire avant inclusion s’il y a des symptômes
    •Association avec la sorivudine et autres analogues inhibiteurs de la DPD comme la brivudine
    •Traitement par millepertuis (Hypericum perforatum)
    •Femme enceinte ou allaitante
    •patient séropositif pour VIH, hépatite B ou C ou autres syndromes d’immunodéficience
    •antecedent de pathologie maligne dans les trois dernières années à l’exception du carcinome basocellulaire de la peau ou du carcinome in situ du col utérin correctement traités
    •Maladie chronique non contrôlée ou infection active incompatible avec une participation à l’étude
    •vaccination (vaccin vivant) dans les 30 jours précédant le début du traitement
    •Personne privée de liberté ou sous tutelle
    •Intervalle QT/QTc > 450 msec pour les hommes et > 470 msec pour les femmes à l’ECG
    •K+ < LIN, Mg²+ < LIN, Ca²+ < LIN
    •Antécédents ou hypersensibilité connue à l’un des agents de chimiothérapie de l’étude ou à leurs excipients
    E.5 End points
    E.5.1Primary end point(s)
    To compare the progression-free survival (PFS) with mFOLFIRINOX regimen versus platinum - etoposide regimen according to the investigator using RECIST v1.1 criteria.
    Comparer la survie sans progression (SSP) entre le bras de traitement mFOLFIRINOX et le bras de traitement platinum – etoposide selon l’investigateur et évaluée selon les critères RECIST 1.1
    E.5.1.1Timepoint(s) of evaluation of this end point
    8 months
    8 mois
    E.5.2Secondary end point(s)
    •PFS according to the centralized review (RECIST v1.1 criteria)
    •Best objective response rate (ORR)
    •Median overall survival (OS)
    •Safety according to NCI CTC V4.0
    •Dose-reductions
    •Quality of life assessed by EORTC QLQ-C30 and EQ-5D-5L
    •To establish a molecular profile within 2 months after tumor sample submission for each patient enrolled in the study and to provide a molecular tumor board report to the treating physician.
    •Frequency of Rb loss in G3 NEC irrespective of the SC or LC subtype
    •Correlation of ORR, PFS and OS under both chemotherapy regimens with molecular alterations (Rb, TP53, MSH2…)
    •SSP selon la relecture centralisée (critères RECIST v1.1)
    •Taux de meilleure réponse objective (TRO)
    •Survie globale (SG)
    •Evènements indésirables selon le NCI CTC V4.0
    •Dose intensité - réductions de dose
    •Qualité de vie évaluée par les questionnaires EORTC QLQ-C30 et EQ-5D-5L
    •Etablir un profil moléculaire dans les 2 mois après l’envoi de l’échantillon de la tumeur pour chaque patient inclus dans l’étude et fournir un compte-rendu de RCP moléculaire à l’investigateur traitant le patient.
    •Nombre de pertes d’expression de Rb (indépendamment du sous-groupe petites cellules ou grandes cellules)
    •Corrélation de TRO, SSP et OS sous les deux bras de traitement avec les altérations moléculaires (Rb, TP53, MSH2…)
    E.5.2.1Timepoint(s) of evaluation of this end point
    8 months
    8 mois
    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 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 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.8.2.3.1Comparator description
    etoposide + sels de platine
    etoposide and platinium
    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 concerned60
    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
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years6
    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 years6
    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: 214
    F.1.3Elderly (>=65 years) No
    F.1.3.1Number of subjects for this age range: 4
    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 Yes
    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 state218
    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)
    investigator decision
    choix de l'investigateur
    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 Decision2020-03-26
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-07-20
    P. End of Trial
    P.End of Trial StatusOngoing
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