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    Summary
    EudraCT Number:2017-004195-58
    Sponsor's Protocol Code Number:MS100070-0029
    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:2021-06-01
    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 ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2017-004195-58
    A.3Full title of the trial
    CAVE (Cetuximab-AVElumab) lung: A single arm phase II clinical study of the combination of avelumab plus cetuximab in the second line treatment of metastatic non small cell lung cancer (NSCLC) patients.
    CAVE (Cetuximab-AVElumab) lung: sperimentazione di fase II a singolo braccio di avelumab in combinazione con cetuximab nel trattamento di II linea dei pazienti con carcinoma del polmone non a piccole cellule (NSCLC).
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Avelumab plus Cetuximab as II lines treatment in NSCLC patients
    Avelumab più Cetuximab come trattamento di II linea in pazienti con carcinoma del polmone non a piccole cellule.
    A.3.2Name or abbreviated title of the trial where available
    CAVE lung
    CAVE lung
    A.4.1Sponsor's protocol code numberMS100070-0029
    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 SponsorA.O.U. Università degli Studi della Campania "Luigi Vanvitelli"
    B.1.3.4CountryItaly
    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 supportMercK KGaA
    B.4.2CountryGermany
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAzienda Ospedaliera Universitaria Seconda Università degli Studi di Napoli
    B.5.2Functional name of contact pointDipartimento Internistica Clinica e
    B.5.3 Address:
    B.5.3.1Street Addressvia pansini 5
    B.5.3.2Town/ cityNapoli
    B.5.3.3Post code80131
    B.5.3.4CountryItaly
    B.5.4Telephone number0815666770
    B.5.5Fax number0815666688
    B.5.6E-maildaniela.renato@hotmail.it
    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 nameBavencio
    D.3.2Product code [NA]
    D.3.4Pharmaceutical form Concentrate for 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 INNAvelumab
    D.3.9.1CAS number 1537032-82-8
    D.3.9.2Current sponsor codeNA
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    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 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 Yes
    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 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 ERBITUX - 5 MG/ML SOLUZIONE PER INFUSIONE - USO ENDOVENOSO- FLACONCINO(VETRO) 20 ML 1 FLACONCINO
    D.2.1.1.2Name of the Marketing Authorisation holderMERCK KGAA
    D.2.1.2Country which granted the Marketing AuthorisationItaly
    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 nameErbitux
    D.3.2Product code [NA]
    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 INNCETUXIMAB
    D.3.9.1CAS number 205923-56-4
    D.3.9.2Current sponsor codeNA
    D.3.9.3Other descriptive nameCETUXIMAB
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    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 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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    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 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
    NSCLC
    Carcinoma del polmone non a piccole cellule
    E.1.1.1Medical condition in easily understood language
    Lung Cancer
    Tumore del polmone
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level HLGT
    E.1.2Classification code 10038666
    E.1.2Term Respiratory and mediastinal neoplasms malignant and unspecified
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    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 the study is to evaluate the efficacy (OS) of avelumab and cetuximab combined in the second line treatment of patients with metastatic NSCLC.
    L’obiettivo primario dello studio è di valutare l’efficacia (OS) della combinazione di avelumab e cetuximab nel trattamento di seconda linea dei pazienti con carcinoma polmonare non a piccole cellule (NSCLC) metastatico.
    E.2.2Secondary objectives of the trial
    To demonstrate superiority with regard to the objective response rate (ORR) of avelumab and cetuximab combined in the second line treatment of patients with metastatic NSCLC.

    To demonstrate superiority with regard to progression free survival (PFS) of avelumab and cetuximab combined in the second line treatment of patients with metastatic NSCLC.

    To determine the safety and tolerability of avelumab and cetuximab combined in the second line treatment of patients with metastatic NSCLC.
    Dimostrare la superiorià in termini di objective response rate (ORR) della combinazione di avelumab e cetuximab nel trattamento di seconda linea dei pazienti con carcinoma polmonare non a piccole cellule (NSCLC) metastatico.

    Dimostrare la superiorià in termini di progression free serviva (PFS) della combinazione di avelumab e cetuximab nel trattamento di seconda linea dei pazienti con carcinoma polmonare non a piccole cellule (NSCLC) metastatico.

    Dimostrare la sicurezza e tollerabilità della combinazione di avelumab e cetuximab nel trattamento di seconda linea dei pazienti con carcinoma polmonare non a piccole cellule (NSCLC) metastatico.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Subjects with histologically confirmed Stage IIIb/IV or recurrent NSCLC who have experienced disease progression.

    Subjects must have progressed after an acceptable therapy defined as follows:
    a. Subjects must have progressed during or after a minimum of 2 cycles of 1 course of a platinum-based combination therapy or immunotherapy or a combination of both administered for the treatment of metastatic disease. A history of continuation (use of a non-platinum agent from initial combination) or switch (use of a different agent) maintenance therapy is permitted provided there was no progression after the initial combination. A switch of agents during treatment for the management of toxicities is also permitted provided there was no progression after the initial combination.
    OR
    b. Subjects must have progressed within 6 months of completion of a platinum-based adjuvant, neoadjuvant, or definitive chemotherapy, or concomitant chemoradiation regimen for locally advanced disease.

    Subjects with non-squamous cell NSCLC of unknown EGFR mutational status or ALK rearrangement will require testing (local laboratory). Subjects with a tumor that harbors an activating EGFR mutation or ALK rearrangement will not be eligible.

    ECOG PS of 0 to 1 at trial entry.
    Soggetti con diagnosi istologica di NSCLC in Stadio IIIb/IV o recidivato che hanno sperimentato progressione di malattia.

    I soggetti devono aver sperimentato progressione di malattia dopo una accettabile linea di trattamento definite come segue:
    a. I soggetti devono aver sperimentato progressione di malattia durante o dopo un minimo di 2 cicli di 1 linea di trattamento con doppietta a base di platino o immunoterapia o una combinazione di entrambi somministrata per il trattamento della malattia metastatica. Una storia di terapia di mantenimento con continuazione (uso di un farmaco non a base di platino da un’iniziale combinazione) o switch (uso di un farmaco diverso) è permesso dimostrando che non c’è stata progressione di malattia dopo il trattamento di combinazione iniziale. Il cambiamento dei farmaci utilizzati durante il trattamento, legato alla tossicità è altresì permesso dimostrando che non c’è stata progressione dopo il trattamento di combinazione iniziale.
    O
    b. I soggetti devono aver sperimentato progressione di malattia entro 6 mesi dal completamento di un trattamento a base di platino neoadiuvante, adiuvante o di un trattamento chemioterapico definitivo o chemio-radioterapico per malattia localmente avanzata.

    I soggetti con NSCLC ad istologia non squamosa non noti per stato mutazionale di EGFR o traslocazione di ALK necessitano di una valutazione molecolare eseguita dai centri partecipanti. I soggetti con neoplasia positiva per mutazione attivante di EGFR o traslocazione di ALK non sono eleggibili.

    ECOG PS 0 o 1 all’inizio del’ingresso nella sperimentazione.
    E.4Principal exclusion criteria
    Systemic anticancer therapy administered after disease progression during or following a platinum-based combination.

    Subjects with non-squamous cell NSCLC whose disease harbors EGFR mutation(s) and/or anaplastic lymphoma kinase (ALK) rearrangement will not be eligible for this trial. Subjects of unknown ALK and/or EGFR mutation status will require testing at screening.

    Subjects receiving immunosuppressive agents (such as steroids) for any reason should be tapered off these drugs before initiation of the trial treatment.

    All subjects with brain metastases, except those meeting the following criteria:
    a. Brain metastases have been treated locally, and
    b. No ongoing neurological symptoms that are related to the brain localization of the disease.

    Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent.
    Terapia sistemica antineoplastica somministrata dopo progressione di malattia durante o successivamente un trattamento di combinazione a base di platino.

    Soggetti con NSCLC ad istologia non squamosa positivi per mutazione(i) attivante(i) di EGFR e/o traslocazione di ALK non sono eleggibili al questa sperimentazione. Soggetti non noti per traslocazione di ALK e/o mutazione EGFR necessitano tali valutazioni durante lo screening.

    Soggetti che ricevono farmaci immunosoppressivi (come i corticosterioidi) per qualsiasi motivo dovrebbero ridurre il dosaggio di questi farmaci fino a sospenderlo prima dell’inzio del trattamento.

    Tutti I soggetti con metastasi encefaliche, eccetto quelli che soddisfano I seguenti criteri:
    a. Metastasi encefaliche sottoposte a trattamenti loco-regionali, e
    b. Assenza di sintomi neurologici in corso correlati con la localizzazione encefalica di malattia.

    Malattia autoimmune attiva che potrebbe peggiorare quando si riceve un agente immunostimolatorio.
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint for the trial is OS time, defined as the interval from enrollment to death for every cause.
    L'endopoint prmario della sperimentazione è l'OS, definita come intervallo dall'arruolamento alla morte per qualsiasi causa.
    E.5.1.1Timepoint(s) of evaluation of this end point
    The survival follow-up continue a maximum of 5 years after the last subject receives the last dose of avelumab and cetuximab.
    Il follow-up per la sopravvivenza continuerà per un massimo di 5 anni dopo che l'ultimo soggetto abbia ricevuto l'ultima dose di avelumab e cetuximab.
    E.5.2Secondary end point(s)
    The overall response rate (ORR) according to RECIST 1.1
    Progression free survival (PFS) according to RECIST 1.1
    The safety profile of the trial drugs as measured by the incidence of AEs, SAEs, clinical laboratory assessments, vital signs, physical examination, ECG parameters, and ECOG PS.
    La overall response rate (ORR) in accordo con i criteri RECIST 1.1
    La progression free survival (PFS) in accordo con i criteri RECIST 1.1
    Il profilo di sicurezza del trattamento sperimentale definito tramite la valutazione dell'incidenza di EA, SAE, valutazione dei parametri di laboratorio, segni vitali, esame obiettivo, ECG e PS secondo ECOG.
    E.5.2.1Timepoint(s) of evaluation of this end point
    60 months
    60 mesi
    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 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 No
    E.8.1.1Randomised No
    E.8.1.2Open No
    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) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial1
    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 concerned5
    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 Information not present in EudraCT
    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 whole trial may be discontinued prematurely in the event of any of the following:
    - new information leading to unfavorable risk-benefit judgment of the trial drug
    - Unfavorable safety findings
    - Sponsor's decision that continuation of the trial is unjustifiable for medical or ethical reasons
    - Poor enrollment of subjects
    L'intero trial può essere prematuramente discontinuato se:
    - si rendono disponobili nuovi dati su rapporto rischio/beneficio non favorevole per il trattamento
    - altre informazioni di sicurezza non favorevoli
    - decisione dello Sponsor basata su motivi clinici/etici
    - scarso arruolamento
    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 months36
    E.8.9.1In the Member State concerned days10
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months36
    E.8.9.2In all countries concerned by the trial days10
    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: 45
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 45
    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 Yes
    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 state90
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 90
    F.4.2.2In the whole clinical trial 90
    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)
    If the trail is not prematurely terminated, the survival follow-up will continue until 5 years after the last subject receives the last dose of avelumab plus cetuximab.
    Se il trial non terminerà prematuramente, il follow-up per la sopravvivenza continuerà fino a 5 anni dopo l'ultima somministrazione di avelumab più cetuximab per l'ultimo soggetto arruolato
    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 Decision2018-05-14
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-05-25
    P. End of Trial
    P.End of Trial StatusOngoing
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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
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