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    Summary
    EudraCT Number:2017-003509-16
    Sponsor's Protocol Code Number:FLIBER
    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:2022-01-20
    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 number2017-003509-16
    A.3Full title of the trial
    Serum cytokine levels as predictors of the efficacy of aflibercept in combination with FOLFIRI in metastatic Colo-Rectal Cancer patients (mCRC)
    Livelli sierici di citochine come predittori di efficacia di aflibercept in combinazione con FOLFIRI in pazienti con Cancro al Colon-Retto metastatico
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Serum cytokine levels as predictors of the efficacy of aflibercept in combination with FOLFIRI in metastatic Colo-Rectal Cancer patients (mCRC)
    Livelli sierici di citochine come predittori di efficacia di aflibercept in combinazione con FOLFIRI in pazienti con Cancro al Colon-Retto metastatico
    A.3.2Name or abbreviated title of the trial where available
    FLIBER
    FLIBER
    A.4.1Sponsor's protocol code numberFLIBER
    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 SponsorFONDAZIONE RICERCA TRASLAZIONALE (FORT)
    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 supportSanofi S.p.A.
    B.4.2CountryItaly
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationCLINICAL RESEARCH TECHNOLOGY
    B.5.2Functional name of contact pointCRO
    B.5.3 Address:
    B.5.3.1Street AddressVia San Leonardo, traversa Migliaro
    B.5.3.2Town/ citySalerno
    B.5.3.3Post code84131
    B.5.3.4CountryItaly
    B.5.4Telephone number089301545
    B.5.5Fax number0897724155
    B.5.6E-mailfliber@cr-technology.com
    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 ZALTRAP - 25 MG/ML - CONCENTRATO PER SOLUZIONE PER INFUSIONE - USO ENDOVENOSO - FLACONE (VETRO) - 100 MG/4 ML - 1 FLACONE
    D.2.1.1.2Name of the Marketing Authorisation holderSANOFI-AVENTIS GROUPE
    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.3.4Pharmaceutical 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 INNAFLIBERCEPT
    D.3.9.2Current sponsor codeAFLIBERCEPT
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNIRINOTECAN CLORIDRATO TRIIDRATO
    D.3.9.2Current sponsor codeIRINOTECAN CLORIDRATO TRIIDRATO
    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.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNFLUOROURACILE
    D.3.9.2Current sponsor codeFLUOROURACILE
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNACIDO FOLINICO
    D.3.9.2Current sponsor codeAcido folinico
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    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.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 Colo-Rectal Cancer
    Cancro al Colon-Retto metastatico
    E.1.1.1Medical condition in easily understood language
    Metastatic Colo-Rectal Cancer
    Cancro al Colon-Retto metastatico
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level PT
    E.1.2Classification code 10052358
    E.1.2Term Colorectal cancer metastatic
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level PT
    E.1.2Classification code 10052358
    E.1.2Term Colorectal cancer metastatic
    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
    To assess progression free survival associated with the study treatment focusing on its relationship with baseline serum levels of IL-8.
    Valutare la Sopravvivenza libera da progressione (PFS) associata al trattamento in studio concentrandosi sulla sua correlazione con i livelli sierici basali di IL-8.
    E.2.2Secondary objectives of the trial
    To assess: Radiologic Response Rate (rRR), Overall Survival (OS), safety profile, associated with the study treatment and their relationship with baseline levels of IL-8
    Valutare: Tasso di Risposta Radiologica (rRR), sopravvivenza globale (OS), profilo di sicurezza, associati al trattamento in studio e la loro correlazione con i livelli sierici basali di IL-8.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Adult age (>= 18 years old);
    2. An Eastern Cooperative Oncology Group (ECOG);
    performance status (PS) of 0 or 1;
    3. Histologically or cytologically proven colorectal
    adenocarcinoma with metastatic disease not menable to potentially curative treatment;
    4. Measurable disease according to the RECIST criteria 1.1;
    5. Documented progression while on or after completion of a single prior oxaliplatin-containing regimen in patients treated in the neoadjuvant and metastatic setting; documented relapsing disease within 6 months of completion of oxaliplatinbased regimen in patients treated in the adjuvant setting;
    6. Aflibercept in combination with irinotecan planned as per standard clinical practice and decision by the treating oncologist;
    7. Any adverse events from prior anticancer therapy must have recovered to grade = 1 ([NCI-CTCAE] version 5.0) before study enrolment;
    8. Patients were to have adequate bone marrow, liver and renal: alanine transaminase (ALT) = 3 × institutional upper limit of normal (ULN) [= 5 × ULN in presence of liver metastases], total bilirubin = 1.5 × institutional ULN [= 2.0 x ULN in presence of liver metastases], neutrophil count = 1.5 x 109/L, platelet count = 100 x 109/L, proteinuria ¿ 1+ on the dipstick, creatinine = 2.5 x institutional ULN or creatinine clearance of =40 mL/min;
    9. Signed written consent form;
    10. Patients of reproductive potential, must use adequate contraception methods;
    1-Età adulta (>= 18 anni);
    2-ECOG performance status di 0 o 1; 3-conferma istologica o citologica di adenocarcinoma colorettale, con malattia metastatica non suscettibile ad un trattamento potenzialmente curativo;
    4-Malattia misurabile in accordo ai criteri RECIST 1.1.; 5-Documentata progressione di malattia durante o dopo il completamento di un singolo regime precedente contenente oxaliplatino in pazienti trattati nel setting neoadiuvante e metastatico;documentata malattia recidiva entro 6 mesi dal completamento del regime basato su oxaliplatino in pazienti trattati nel setting adiuvante;
    6-Aflibercept in combinazione con irinotecano pianificato come da pratica clinica e su decisione del medico oncologo;
    7-Eventuali Eventi avversi derivanti da precedenti terapie antineoplastiche devono essere recuperate al grado = 1 ([NCI-CTCAE] versione 5.0 )prima dell’arruolamento;
    8-Pazienti con adeguata funzionalità al midollo osseo, al fegato e renale: alanina transaminasi (ALT) = 3 × institutional upper limit of normal (ULN) [= 5 × ULN in presenza di metastasi epatiche], bilirubina totale = 1.5 × institutional ULN [= 2.0 x ULN in presenza di metastasi epatiche], conta di neutrofili = 1.5 x 109/L, conta di piastrine = 100 x 109/L, proteinuria ¿ 1+ al dipstick, creatinina = 2.5 x institutional ULN o clearance della creatinina =40 mL/min.;
    9- Consenso informato scritto;
    10- Pazienti con potenziale riproduttivo, devono usare adeguati metodi contraccettivi;
    E.4Principal exclusion criteria
    1. Radiation therapy or any previous anti-neoplastic systemic treatment within the past 28 days before study enrollment;
    2. History of major surgery within 28 days before study enrollment; 3. Known prior malignancies or known brain metastases ( patients with adequately treated basal cell or squamous cell skin cancer,
    carcinoma in situ of the cervix, or any other cancer from which the patient had been disease-free for more than 10 years are permitted);
    4. Severe acute or chronic medical condition that may impair the ability to participate in the study or may interfere with the interpretation of results;
    5. Any contraindication to the administration of aflibercept, irinotecan, 5-fluorouracil or folinic acid;
    6. History of any auto-immune or rheumatic disease; any active bacterial or viral infection;
    7. History of uncontrolled hypertension and diabetes within 3 months before enrollment;
    8. History of daily use of corticosteroids or immune-suppressive medications;
    9. Deep vein thrombosis within 4 weeks before treatment;
    10. Pregnant and breast-feeding women;
    11. Patients of reproductive potential who refuse to use effective methods of contraception;
    1. Radioterapia o qualsiasi precedente trattamento sistemico anti-neoplastico negli ultimi 28 giorni precedenti l’arruolamento;
    2. Storia di chirurgia maggiore entro 28 giorni precedenti l’arruolamento; 3. Note neoplasie precedenti o metastasi al cervello (sono invece ammessi pazienti con cancro a cellule basali o a cellule squamose adeguatamente trattati, con carcinoma in situ della cervice o qualsiasi altro tumore da cui il paziente risulta libero da malattia da più di 10 anni).
    4. Condizione medica severa acuta o cronica che può compromettere la capacità di partecipare allo studio o può interferire con l'interpretazione dei risultati;
    5. Qualsiasi controindicazione alla somministrazione di aflibercept, irinotecano, 5-fluorouracile o acido folinico;
    6. Storia di qualsiasi malattia autoimmune o reumatica; qualsiasi infezione batterica o virale attiva;
    7. Storia di ipertensione incontrollata e diabete nei 3 mesi precedenti l’arruolamento;
    8. Storia dell'uso quotidiano di corticosteroidi o farmaci immunosoppressori;
    9. Trombosi venosa profonda entro le 4 settimane precedenti il trattamento;
    10. Donne in stato di gravidanza e allattamento;
    11. Pazienti in età riproduttiva che rifiutano di utilizzare metodi efficaci di contraccezione;
    E.5 End points
    E.5.1Primary end point(s)
    The primary end point of the study is progression free survival (PFS), with the objective to estimate the difference in PFS between the two groups defined on the basis of their baseline IL-8 levels (>= vs. < than median).
    L’Endpoint primario dello studio è la Sopravvivenza libera da progressione (PFS), con l'obiettivo di stimare la differenza in PFS tra i due gruppi definiti sulla base dei loro livelli di IL-8 al basale (>= VS. < della mediana)
    E.5.1.1Timepoint(s) of evaluation of this end point
    36 months
    36 mesi
    E.5.2Secondary end point(s)
    The secondary endpoints of the study are: • Radiologic Response Rate (rRR) • Overall Survival (OS) • Safety profile
    Gli end point secondari dello studio sono: - Tasso di Risposta Radiologica (rRR) - Sopravvivenza globale (OS) - Profilo di sicurezza
    E.5.2.1Timepoint(s) of evaluation of this end point
    36 months
    36 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 No
    E.6.4Safety No
    E.6.5Efficacy No
    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 Yes
    E.6.13.1Other scope of the trial description
    To assess progression free survival associated with the study treatment and its relationship with baseline serum levels of IL-8.
    Valutare la Sopravvivenza libera da progressione (PFS) associata al trattamento in studio e la sua correlazione con i livelli sierici basali di IL-8.
    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) No
    E.7.4Therapeutic use (Phase IV) Yes
    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 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 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
    Exstimed LVLS December 2020
    LVLS stimata Dicembre 2020
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years0
    E.8.9.1In the Member State concerned months36
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years0
    E.8.9.2In all countries concerned by the trial months36
    E.8.9.2In all countries concerned by the trial 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: 62
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 62
    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 state124
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 124
    F.4.2.2In the whole clinical trial 124
    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)
    Patients who stop the study treatment will be followed up on every 3 months until the end of
    the study or until death, whichever occurs first.
    Pazienti che interrompono il tratamento saranno seguiti ogni 3 mesi fino alla fine dello studio o fino al decesso, a seconda di cosa si verifica prima.
    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 Decision2018-03-02
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-02-21
    P. End of Trial
    P.End of Trial StatusOngoing
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