Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

  • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).


    The EU Clinical Trials Register currently displays   44334   clinical trials with a EudraCT protocol, of which   7366   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).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2018-003585-14
    Sponsor's Protocol Code Number:D-US-60010-001
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2021-06-15
    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
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2018-003585-14
    A.3Full title of the trial
    An open-label, randomised, multicentre, phase III study of irinotecan liposome injection, oxaliplatin, 5-fluorouracil/leucovorin versus nabpaclitaxel plus gemcitabine in subjects who have not previously received chemotherapy for metastatic adenocarcinoma of the pancreas
    Studio di fase III in aperto, randomizzato, multicentrico, su irinotecan liposomiale per iniezione, oxaliplatino, 5-fluorouracile/leucovorina rispetto a nab-paclitaxel più gemcitabina in soggetti non sottoposti a precedente chemioterapia per adenocarcinoma pancreatico metastatico.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study to compare 2 chemotherapy, one with Irinotecan liposome injection in addition to combination of chemotherapy and one with standard chemotherapy in patients with pancreatic cancer
    Studio per confrontare 2 chemioterapie, una con irinotecan liposomiale per iniezione in aggiunta alla combinazione di chemioterapia e una con chemioterapia standard in pazienti con carcinoma pancreatico
    A.3.2Name or abbreviated title of the trial where available
    Napoli 3
    Napoli 3
    A.4.1Sponsor's protocol code numberD-US-60010-001
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT04083235
    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 SponsorIPSEN BIOSCIENCE, 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 supportIpsen Bioscience, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationIpsen Bioscience, Inc.
    B.5.2Functional name of contact pointGlobal Drug Development
    B.5.3 Address:
    B.5.3.1Street Address650 East Kendall Street
    B.5.3.2Town/ cityCambridge
    B.5.3.3Post codeMA 02142
    B.5.3.4CountryUnited States
    B.5.4Telephone number0016176798000
    B.5.5Fax number0016176798752
    B.5.6E-mailct-application@ipsen.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 Onivyde pegylated liposomal
    D.2.1.1.2Name of the Marketing Authorisation holderLes Laboratoires Servier - EU/1/16/1130/001
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/11/933
    D.3 Description of the IMP
    D.3.1Product nameIrinotecan Liposome Injection
    D.3.2Product code [MM-398]
    D.3.4Pharmaceutical form Concentrate for solution for injection
    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.3.9.2Current sponsor codeMM-398
    D.3.9.4EV Substance CodeSUB08295MIG
    D.3.10 Strength
    D.3.10.1Concentration unit µg/ml microgram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number4300
    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 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.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 OXALIPLATIN
    D.2.1.1.2Name of the Marketing Authorisation holderAccord Healthcare, Inc.
    D.2.1.2Country which granted the Marketing AuthorisationUnited States
    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 name-
    D.3.2Product code [-]
    D.3.4Pharmaceutical form Concentrate for solution for injection
    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 INNOXALIPLATINO
    D.3.9.1CAS number 61825-94-3
    D.3.9.2Current sponsor code-
    D.3.9.4EV Substance CodeSUB09490MIG
    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 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 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.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 Fluorouracil
    D.2.1.1.2Name of the Marketing Authorisation holderAccord Healthcare, Inc.
    D.2.1.2Country which granted the Marketing AuthorisationUnited States
    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 name-
    D.3.2Product code [-]
    D.3.4Pharmaceutical form Concentrate for solution for injection
    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 INNFLUOROURACILE
    D.3.9.1CAS number 51-21-8
    D.3.9.2Current sponsor code-
    D.3.9.4EV Substance CodeSUB07721MIG
    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.3.11 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 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.IMP: 4
    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 ABRAXANE - 5 MG/ML - POLVERE PER SOSPENSIONE PER INFUSIONE - USO ENDOVENOSO- 100 MG - FLACONCINO(VETRO) 1 FLACONCINO
    D.2.1.1.2Name of the Marketing Authorisation holderCELGENE EUROPE B.V.
    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 name-
    D.3.2Product code [-]
    D.3.4Pharmaceutical form Powder for solution for injection
    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 INNPaclitaxel
    D.3.9.1CAS number 33069-62-4
    D.3.9.2Current sponsor code-
    D.3.9.4EV Substance CodeSUB09583MIG
    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 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 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.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 Gemcitabine
    D.2.1.1.2Name of the Marketing Authorisation holderAccord Healthcare Inc.
    D.2.1.2Country which granted the Marketing AuthorisationUnited States
    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 name-
    D.3.2Product code [-]
    D.3.4Pharmaceutical form Powder and solvent for solution for injection
    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 INNGEMCITABINA
    D.3.9.1CAS number 95058-81-4
    D.3.9.2Current sponsor code-
    D.3.9.4EV Substance CodeSUB07892MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    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 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.IMP: 6
    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 Leucovorin Calcium
    D.2.1.1.2Name of the Marketing Authorisation holderMylan Institutional LLC.
    D.2.1.2Country which granted the Marketing AuthorisationUnited States
    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 name-
    D.3.2Product code [-]
    D.3.4Pharmaceutical form Lyophilisate for solution for injection
    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 INNLeucovorin Calcium
    D.3.9.1CAS number 1492-18-8
    D.3.9.2Current sponsor code-
    D.3.9.4EV Substance CodeSUB13910MIG
    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 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 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
    Previously Untreated, Metastatic Pancreatic Adenocarcinoma
    Adenocarcinoma pancreatico precedentemente non trattato, metastatico
    E.1.1.1Medical condition in easily understood language
    Pancreatic Cancer
    Tumore Pancreatico
    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 LLT
    E.1.2Classification code 10033599
    E.1.2Term Pancreatic adenocarcinoma metastatic
    E.1.2System Organ Class 100000004864
    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 evaluate the efficacy of the regimen of irinotecan liposome injection + oxaliplatin + 5 fluorouracil (5-FU)/leucovorin (LV) versus nab paclitaxel + gemcitabine in improving overall survival (OS) in subjects who have not previously received chemotherapy for metastatic adenocarcinoma of the pancreas.
    L’obiettivo primario di questo studio è valutare l’efficacia del regime di irinotecan liposomiale per iniezione + oxaliplatino + 5 fluorouracile (5-FU)/leucovorina (LV) rispetto a nab-paclitaxel + gemcitabina nel miglioramento della sopravvivenza complessiva (OS) in soggetti che non hanno precedentemente ricevuto una chemioterapia per l’adenocarcinoma metastatico del pancreas.
    E.2.2Secondary objectives of the trial
    The secondary objectives of this study are as follows:
    • To evaluate progression free survival (PFS) according to Response Evaluation Criteria in Solid Tumours (RECIST) Version 1.1 guidelines
    • To evaluate the overall response rate (ORR) according to RECIST Version 1.1 guidelines
    • To evaluate the safety of this regimen in this patient population.
    Gli obiettivi secondari di questo studio sono i seguenti:
    • Valutare la sopravvivenza libera da progressione (PFS) secondo le linee guida dei Criteri di valutazione della risposta nei tumori solidi (RECIST) Versione 1.1
    • Valutare il tasso di risposta complessiva (ORR) secondo le linee guida RECIST Versione 1.1
    • Valutare la sicurezza di questo regime in questa popolazione di pazienti.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    (1) Subject has been informed about the nature of the study, and has agreed to participate in the study, and signed the ICF prior to participation in any study-related activities.
    (2) Male or non-pregnant and non-lactating female and =18 years of age:
    (a) Females of child-bearing potential must test negative for pregnancy at the time of screening based on a urine or serum pregnancy test. Postmenopausal women are defined as those that have an absence of menstruation for at least 2 years. If necessary, follicle stimulating hormone results >50 IU/L at screening are confirmatory in the absence of a clear postmenopausal history. Female subjects of reproductive potential must agree to use a highly effective method of birth control, during the study and for 6 months following the last dose of study medication.
    (b) Male subjects must agree to use condoms during the study and for 6 months following the last dose of study medication.
    (3) Histological or cytologically confirmed adenocarcinoma of the pancreas that has not been previously treated in the metastatic setting.
    (4) Initial diagnosis of metastatic disease must have occurred =6 weeks prior to screening.
    (5) Subject has one or more metastatic tumours measurable by CT scan (or MRI, if the subject is allergic to CT contrast media) according to RECIST Version 1.1 criteria.
    (6) ECOG performance status of 0 or 1 at screening and within 7 days prior to randomisation. Two observers will be required to assess ECOG. If discrepant, the one with the highest assessment will be considered true.
    (7) Subject has adequate biological parameters as demonstrated by the following blood counts:
    (a) Absolute neutrophil count (ANC) =1500/mm3 without the use of hemopoietic growth factors within the last 7 days prior to randomisation
    (b) Platelet count =100,000/mm3
    (c) Haemoglobin (Hgb) =9 g/dL obtained =14 days prior to randomisation.
    (8) Adequate hepatic function as evidenced by:
    (a) Serum total bilirubin =1.5x upper limit of normal (ULN) (biliary drainage is allowed for biliary obstruction), and (b) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =2.5x ULN (=5x ULN is acceptable if liver
    metastases are present).
    (9) Adequate renal function with a creatinine clearance (CLCR) of >30 mL/min. Actual body weight should be used for calculating CLCR using the Cockcroft Gault Equation: CLCR (mL/min) = ((140–Age [years]) * (Weight [kg]/(Serum Creatinine
    [mg/dL]*72). Multiply the result by 0.85 if the subject is female. For subjects with a body mass index (BMI) >30 kg/m2, adjusted body weight should be used instead.
    (10) Electrocardiogram (ECG) without any clinically significant findings (QT interval corrected by Fridericia's formula (QTcF) <480 msec and no
    known arrhythmias), and per the investigator's assessment.
    (11) Adequate coagulation studies (obtained =14 days prior to randomisation) as demonstrated by prothrombin time and partial thromboplastin time within normal limits (=1.5 x ULN). (Subjects on warfarin or other vitamin K antagonists should be discussed with the sponsor).
    (12) Subject has no clinically significant abnormalities in urinalysis results (obtained within the last 7 days prior to randomisation), per the investigator's assessment.
    (13) Subjects infected with human immunodeficiency virus (HIV) are eligible if they meet all the following criteria:
    Please refer to the Protocol Synopsis
    (1) Il soggetto è stato informato circa la natura dello studio, ha accettato di parteciparvi e ha firmato il modulo di consenso informato prima di sottoporsi a qualsiasi attività correlata allo studio.
    (2) Uomini o donne non in gravidanza e non in fase di allattamento di età =18 anni:
    (a) Le donne potenzialmente fertili non devono essere in gravidanza al momento dello screening in base a un test di gravidanza sulle urine o sul siero risultato negativo. Le donne in post-menopausa sono definite come donne che non manifestano mestruazioni da almeno 2 anni. Se necessario, possono essere usati come conferma i risultati dell’ormone follicolo-stimolante >50 UI/l allo screening in assenza di una chiara anamnesi postmenopausale. I soggetti di sesso femminile potenzialmente fertili devono accettare di utilizzare un metodo contraccettivo altamente efficace durante lo studio e per 6 mesi dopo l’ultima dose del farmaco in studio.
    (b) I soggetti di sesso maschile devono acconsentire all’uso del profilattico durante lo studio e per 6 mesi dopo l’ultima dose del farmaco in studio.
    (3) Adenocarcinoma del pancreas confermato istologicamente o citologicamente che non è stato precedentemente trattato nel contesto metastatico.
    (4) La diagnosi iniziale di malattia metastatica deve essere stata formulata =6 settimane prima dello screening.
    (5) Il soggetto presenta uno o più tumori metastatici misurabili mediante tomografia computerizzata (TC) (o MRI se il soggetto è allergico ai mezzi di contrasto per TC) secondo i criteri RECIST Versione 1.1.
    (6) Stato della performance secondo il ECOG pari a 0 o 1 allo screening e nei 7 giorni precedenti la randomizzazione. Per valutare il punteggio ECOG saranno necessari due osservatori. In caso di discrepanze, sarà considerato reale il valore con la valutazione più alta.
    (7) Il soggetto presenta parametri biologici adeguati, come dimostrato dalle seguenti conte ematiche:
    (a) Conta assoluta dei neutrofili (ANC) =1.500/mm3 senza l’uso di fattori di crescita emopoietici negli ultimi 7 giorni prima della randomizzazione;
    (b) Conta piastrinica =100.000/mm3;
    (c) Emoglobina (Hgb) =9 g/dl misurata =14 giorni prima della randomizzazione.
    (8) Funzione epatica adeguata come evidenziato da:
    (a) Bilirubina totale sierica =1,5 volte il limite superiore della norma (ULN) (il drenaggio biliare è consentito in caso di ostruzione biliare) e
    (b) Aspartato aminotransferasi (AST) e alanina aminotransferasi (ALT) =2,5 volte l’ULN (un valore =5 volte l’ULN è accettabile se sono presenti metastasi epatiche).
    (9) Funzione renale adeguata con clearance della creatinina (CLCR) >30 ml/min. Il peso corporeo effettivo deve essere utilizzato per calcolare la CLCR usando l’equazione di Cockcroft Gault: CLCR (ml/min) = (140 - età [anni]) * (peso [kg]/(creatinina sierica [mg/dl]*72). Moltiplicare il risultato per 0,85 se il soggetto è di sesso femminile. Per soggetti con indice di massa corporea (BMI) >30 kg/m2, è necessario utilizzare il peso corporeo corretto.
    (10) ECG senza riscontri clinicamente significativi (intervallo QT corretto mediante la formula di Fridericia [QTCf] <480 msec e nessuna aritmia nota) e in base alla valutazione dello sperimentatore.
    (11) Studi di coagulazione adeguati (eseguiti =14 giorni prima della randomizzazione) come dimostrato dal tempo di protrombina e dal tempo di tromboplastina parziale entro i limiti normali (=1,5 x ULN) (i soggetti trattati con warfarin o altri antagonisti della vitamina K devono essere discussi con lo sponsor).
    (12) Il soggetto non presenta anomalie clinicamente significative nei risultati delle analisi delle urine, in base alla valutazione dello sperimentatore.
    (13) I soggetti con infezione da virus dell’immunodeficienza umana (HIV) sono eleggibili se soddisfano i seguenti criteri:
    Si invita a far riferimento alla Sinossi del Protocollo
    E.4Principal exclusion criteria
    (1) Any other medical or social condition deemed by the investigator to be likely to interfere with a subject's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results.
    (2) Unwilling or unable to comply with study procedures and/or study visits.
    (3) Prior treatment of pancreatic cancer in the metastatic setting with surgery, radiotherapy, chemotherapy or investigational therapy:
    (a) Palliative radiotherapy is permitted (b) Placement of biliary stent/tube is permitted.
    (4) Prior treatment of pancreatic adenocarcinoma with chemotherapy in the adjuvant setting, except those where at least 12 months have elapsed since completion of the last dose and no persistent treatmentrelated toxicities are present.
    (5) Subject has only localised advanced disease.
    (6) Documented serum albumin <3 g/dL at screening visit and within 7 days prior to randomisation if randomisation occurs more than 72 hours post screening.
    (7) Known history of central nervous system metastases.
    (8) Clinically significant gastrointestinal disorder including hepatic disorders, bleeding, inflammation, occlusion, diarrhoea >Grade 1, malabsorption syndrome, ulcerative colitis, inflammatory bowel disease or partial bowel obstruction.
    (9) History of any second malignancy in the last 2 years; subjects with prior history of in situ cancer or basal or squamous cell skin cancer are eligible. Subjects with a history of other malignancies are eligible if they have been continuously disease free for at least 2 years prior to screening. Subjects who have a concurrent malignancy that is clinically stable and does not require tumour-directed treatment are eligible.
    (10) Known hypersensitivity to any of the components of irinotecan liposome injection, other liposomal products, or any components of 5-FU, LV or oxaliplatin.
    (11) Known hypersensitivity to any of the components of nab-paclitaxel or gemcitabine.
    (12) Concurrent illnesses that would be a relative contraindication to trial participation such as active cardiac or liver disease, including:
    (a) Severe arterial thromboembolic events (myocardial infarction, unstable angina pectoris, stroke) less than 6 months before screening (b) High cardiovascular risk, including, but not limited to, recent coronary stenting or myocardial infarction in the past year prior to screening (c) New York Heart Association (NYHA) Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure (d) Known historical or active infection with hepatitis B, or active infection with hepatitis C
    (13) Active infection or an unexplained fever >38.5°C during screening visits or on the first scheduled day of dosing, which in the investigator's opinion might compromise the subject's participation in the study or affect the study outcome.
    (14) Major surgery, other than diagnostic surgery, within 4 weeks prior to randomisation.
    (15) Use of strong inhibitors or inducers of CYP3A, CYP2C8 and UGT1A1. Subjects are ineligible if: - they are unable to discontinue the use of strong inhibitors of CYP3A, CYP2C8 and UGT1A1 at least 1 week prior to randomisation - they are unable to discontinue the use of strong CYP3A and CYP2C8 inducers at least 2 weeks prior to randomisation.
    (16) There is presence of any contraindications outlined in the Contraindications or Warnings and Precautions sections of the investigator brochure (IB) for irinotecan liposome injection, or in the prescribing information for 5-FU, LV or oxaliplatin.
    (17) There is presence of any contraindications outlined in the Contraindications or Special Warnings and Precautions sections of the product prescribing information for nab paclitaxel or gemcitabine.
    (18) Neuroendocrine or acinar pancreatic carcinoma.
    Please refer to Protocol Synopsis for full list
    (1) Qualsiasi altra condizione medica o sociale che, a parere dello sperimentatore, potrebbe interferire con la capacità del soggetto di firmare il consenso informato, collaborare e partecipare allo studio, o interferire con l’interpretazione dei risultati.
    (2) Riluttanza o incapacità di rispettare le procedure dello studio e/o le visite dello studio.
    (3) Precedente trattamento del carcinoma pancreatico nel contesto metastatico con chirurgia, radioterapia, chemioterapia o terapia sperimentale:
    (a) La radioterapia palliativa è consentita;
    (b) È consentito il posizionamento di stent/catetere biliare.
    (4) Precedente trattamento dell’adenocarcinoma pancreatico con chemioterapia nel contesto adiuvante, ad eccezione di coloro in cui sono trascorsi almeno 12 mesi dal completamento dell’ultima dose e non sono presenti tossicità persistenti correlate al trattamento.
    (5) Il soggetto presenta solo malattia avanzata localizzata.
    (6) Albumina sierica documentata <3 g/dl alla visita di screening e nei 7 giorni precedenti la randomizzazione, se la randomizzazione avviene più di 72 ore dopo lo screening.
    (7) Anamnesi nota di metastasi al sistema nervoso centrale (SNC).
    (8) Disturbo gastrointestinale clinicamente significativo, tra cui disturbi epatici, sanguinamento, infiammazione, occlusione, diarrea di grado >1, sindrome da malassorbimento, colite ulcerosa, malattia infiammatoria intestinale od ostruzione intestinale parziale.
    (9) Anamnesi di qualsiasi secondo tumore maligno negli ultimi 2 anni; i soggetti con anamnesi pregressa di tumore in situ o carcinoma cutaneo basocellulare o squamocellulare sono eleggibili. I soggetti con anamnesi di altre neoplasie maligne sono idonei se sono rimasti costantemente liberi da malattia da almeno 2 anni prima dello screening. I soggetti che presentano una neoplasia maligna concomitante che risulti clinicamente stabile e non necessiti di trattamento diretto al tumore sono eleggibili.
    (10) Ipersensibilità nota a uno qualsiasi dei componenti di irinotecan liposomiale per iniezione, altri prodotti liposomiali o qualsiasi componente di 5-FU, LV od oxaliplatino.
    (11) Ipersensibilità nota a uno qualsiasi dei componenti di nab-paclitaxel o gemcitabina.
    (12) Malattie concomitanti che rappresenterebbero una relativa controindicazione alla partecipazione alla sperimentazione, come malattia cardiaca o epatica attiva, tra cui:
    (a) Eventi tromboembolici arteriosi gravi (infarto miocardico, angina pectoris instabile, ictus) meno di 6 mesi prima dello screening;
    (b) Elevato rischio cardiovascolare, tra cui, a titolo esemplificativo, recente stent coronarico o infarto miocardico nell’ultimo anno precedente allo screening;
    (c) Insufficienza cardiaca congestizia di classe III o IV secondo la New York Heart Association (NYHA), aritmie ventricolari o pressione arteriosa non controllata;
    (d) Infezione storica o attiva nota con epatite B o infezione attiva con epatite C;
    (13) Infezione attiva o febbre inspiegabile >38,5 °C durante le visite di screening o il primo giorno programmato di somministrazione che, a giudizio dello sperimentatore, potrebbe compromettere la partecipazione del soggetto allo studio o influire sull’esito dello studio.
    (14) Intervento chirurgico maggiore, diverso dall’intervento diagnostico, nelle 4 settimane precedenti la randomizzazione.
    (15) Uso di forti inibitori o induttori di CYP3A, CYP2C8 e UGT1A1. I soggetti non sono eleggibili se:
    -non sono in grado di interrompere l’uso di forti inibitori di CYP3A, CYP2C8 e UGT1A1 almeno 1 settimana prima della randomizzazione;
    -non sono in grado di interrompere l’uso di forti induttori di CYP3A e CYP2C8 almeno 2 settimane prima della randomizzazione.

    Si prega di fare riferimento alla Sinossi del Protocollo per la lista completa
    E.5 End points
    E.5.1Primary end point(s)
    The primary efficacy endpoint is the overall survival of subjects treated with irinotecan liposome injection+oxaliplatin+5 FU/LV compared to subjects treated with nab paclitaxel+gemcitabine.
    L’endpoint primario di efficacia è la OS dei soggetti trattati con irinotecan liposomiale per iniezione + oxaliplatino + 5-FU/LV rispetto ai soggetti trattati con nab paclitaxel + gemcitabina.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Subjects will be followed in the study until death to assess OS time. Subjects who have terminated study medication treatment will have follow-up every 2 months to determine survival status.
    I soggetti saranno seguiti nello studio fino al decesso per valutare il tempo di OS. I soggetti che hanno interrotto il trattamento con i farmaci in studio avranno un follow-up ogni 2 mesi per determinare lo stato di sopravvivenza.
    E.5.2Secondary end point(s)
    The secondary efficacy endpoints (PFS and ORR) will only be evaluated if the primary efficacy endpoint demonstrates superiority for irinotecan liposome injection+oxaliplatin+5 FU/LV over nabpaclitaxel+ gemcitabine. Investigator-assessed tumour response will be used in efficacy analysis.
    - Plasma concentrations of total irinotecan, SN-38, oxaliplatin and 5-FU in the combination therapies will be used to characterise corresponding PK parameters using a nonlinear mixed effects approach. Individual PK parameters will be estimated if warranted by the data. Graphical exploration will be performed to investigate any relationship between PK and PD endpoints. If a trend is shown, PK/PD modelling will be performed and reported separately.
    - Safety will be monitored through continuous reporting of AEs and serious adverse events (SAEs), laboratory abnormalities, and incidence of subjects experiencing dose modifications (including dose reductions, dose omissions and dose delays) and/or premature discontinuation of study medication (and reason for discontinuation).
    The safety evaluations include:
    • AEs
    • Clinical laboratory assessments
    • ECG findings
    • Complete physical examination including the evaluation of ECOG, vital signs, measurements and body weight. An independent data and monitoring committee (IDMC) will be established for this study to operate as an independent expert advisory group with the primary responsibility of monitoring the safety of enroled subjects by reviewing the clinical data at scheduled time points described in the IDMC Charter, as well as on an ad hoc basis, as needed.
    The IDMC will additionally review the safety and efficacy of the interim analyses and make appropriate recommendations based on those results.
    Gli endpoint secondari di efficacia (PFS e ORR) saranno valutati solo se l’endpoint primario di efficacia dimostra superiorità per irinotecan liposomiale per iniezione + oxaliplatino + 5-FU/LV rispetto a nab-paclitaxel + gemcitabina. La risposta tumorale valutata dallo sperimentatore sarà utilizzata nell’analisi di efficacia.
    - Le concentrazioni plasmatiche di irinotecan totale, SN-38, oxaliplatino e 5-FU nelle terapie combinate saranno utilizzate per caratterizzare i parametri PK corrispondenti utilizzando un approccio non lineare a effetti misti. I singoli parametri PK saranno stimati se giustificati dai dati. Sarà eseguita un’esplorazione grafica per esaminare eventuali rapporti tra endpoint di PK e farmacodinamica (PD). Se viene mostrata una tendenza, sarà eseguita un’analisi di modelli PK/PD che verrà riportata separatamente.
    - La sicurezza sarà monitorata mediante segnalazione continua di EA ed eventi avversi seri (SAE), anomalie di laboratorio e incidenza di soggetti che manifestano modifiche della dose (comprese riduzioni della dose, omissioni della dose e ritardi della dose) e/o interruzione prematura del farmaco in studio (e motivo dell’interruzione).
    Le valutazioni di sicurezza includono:
    • EA;
    • Valutazioni cliniche di laboratorio;
    • Risultati ECG;
    • Esame obiettivo completo, compresa la valutazione dell’ECOG, segni vitali, misurazioni e peso corporeo.
    Queste valutazioni di sicurezza saranno eseguite dalla firma dell’ICF per tutta la durata dello studio fino a 30 giorni dopo l’ultima somministrazione del trattamento dello studio.
    Per questo studio sarà istituito un Comitato indipendente per il monitoraggio dei dati (IDMC) per operare come gruppo di consulenza esperto indipendente con la responsabilità primaria di monitorare la sicurezza dei soggetti arruolati, esaminando i dati clinici in punti temporali programmati descritti nello Statuto dell’IDMC, nonché su base ad hoc, secondo necessità.
    L’IDMC esaminerà inoltre la sicurezza e l’efficacia delle analisi ad interim e fornirà raccomandazioni appropriate sulla base di tali risultati.
    E.5.2.1Timepoint(s) of evaluation of this end point
    These safety evaluations will be performed from ICF signature, throughout the study to 30 days after the last study treatment administration.
    Subjects will have CT scan (or MRI if the subject is allergic to CT contrast media) performed every 8 weeks that will be evaluated by the investigator site using RECIST guidelines Version 1.1 for complete response, partial response, stable disease or progressive disease.
    Queste valutazioni di sicurezza saranno eseguite dalla firma dell'ICF, durante lo studio fino a 30 giorni dopo l'ultima somministrazione del trattamento dello studio.
    I soggetti saranno sottoposti a TAC (o risonanza magnetica se il soggetto è allergico ai mezzi di contrasto CT) eseguita ogni 8 settimane che saranno valutati dal sito dello sperimentatore utilizzando le linee guida RECIST Versione 1.1 per una risposta completa, risposta parziale, malattia stabile o malattia progressiva.
    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 Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Biobanking
    Biobancaggio
    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 Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group Yes
    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.8.2.4Number 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 concerned12
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA110
    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
    Australia
    Brazil
    Canada
    Chile
    Israel
    Russian Federation
    Turkey
    United States
    Austria
    Belgium
    France
    Germany
    Hungary
    Italy
    Poland
    Spain
    United Kingdom
    Czechia
    Argentina
    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
    The study will be considered to have ended when 564 overall survival (OS) events have occurred. It is anticipated that approximately 2.5 years from first subject, first visit to last subject, last visit will be needed to reach this number of events.. The study will be finally completed when all subjects have died, are lost to follow-up or withdraw consent
    Lo studio sarà considerato concluso quando si saranno veriificati 564 eventi di sopravvivenza complessiva (OS). Si prevede che per raggiungere questo numero di eventi saranno necessari circa 2,5 anni dal primo soggetto, prima visita all'ultimo soggetto, ultima visita. Lo studio sarà infine completato quando tutte i soggetti saranno deceduti, saranno lost to follow-up o ritireranno il consenso
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months6
    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: 500
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 250
    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 state53
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 375
    F.4.2.2In the whole clinical trial 750
    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)
    No post trial treatment planned
    Non sono pianificati trattamenti post studio
    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 Decision2020-04-02
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-01-22
    P. End of Trial
    P.End of Trial StatusCompleted
    For support, Contact us.
    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
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Tue May 06 14:58:50 CEST 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA