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 are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   42174   clinical trials with a EudraCT protocol, of which   6938   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 in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .

    Clinical Trials marked as "Trial now transitioned" were transitioned to the Clinical Trial Regulation 536/2014 and can be further followed in the Clinical Trial Information System  
     
    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:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:GB - no longer in EU/EEA
    Date on which this record was first entered in the EudraCT database:2020-01-15
    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 ConcernedUK - MHRA
    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 nab-paclitaxel plus gemcitabine in subjects who have not previously received chemotherapy for metastatic adenocarcinoma of the pancreas
    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
    A.3.2Name or abbreviated title of the trial where available
    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 number001617679 8000
    B.5.5Fax number001617679 8752
    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
    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 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.3.9.2Current sponsor codeMM-398
    D.3.9.3Other descriptive nameliposomal irinotecan
    D.3.9.4EV Substance CodeSUB08295MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number4.3
    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 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.3.4Pharmaceutical 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 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/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 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 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.3.4Pharmaceutical 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 INNFLUOROURACIL
    D.3.9.1CAS number 51-21-8
    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 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 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
    D.2.1.1.2Name of the Marketing Authorisation holderAbraxis BioScience Australia Pty Ltd.
    D.2.1.2Country which granted the Marketing AuthorisationAustralia
    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 Powder for suspension 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.3.9.3Other descriptive namePaclitaxel- albumin bound
    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 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 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.3.4Pharmaceutical form Powder 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 INNGEMCITABINE
    D.3.9.1CAS number 95058-81-4
    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 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: 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.3.4Pharmaceutical form Lyophilisate for suspension 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.3.9.3Other descriptive nameFOLINIC ACID
    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 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
    Previously Untreated, Metastatic Pancreatic Adenocarcinoma
    E.1.1.1Medical condition in easily understood language
    Pancreatic Cancer
    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.
    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.
    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 (i.e. fertile, following menarche and until becoming postmenopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy) must test negative for pregnancy at the time of screening based on a urine or serum pregnancy test. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. 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 (see also Appendix 4).
    (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) Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening and within 7 days prior to randomisation.
    (7) Subject has adequate biological parameters as demonstrated by the following blood counts:
    (a) Absolute neutrophil count (ANC) ≥2000/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) <450 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:
    (a) CD4 count is ≥350 cells/uL, viral load is undetectable, and not taking prohibited cytochrome (CYP)-interacting medications
    (b) Probable long-term survival with HIV if cancer were not present
    (c) Stable on a highly active antiretroviral therapy (HAART) regimen for ≥4 weeks and willing to adhere to their HAART regimen with minimal overlapping toxicity and drug-drug interactions with the experimental agents in this study
    (d) HIV is not multi-drug resistant
    (e) Taking medication and/or receiving antiretroviral therapy that does not interact or have overlapping toxicities with the study medication.
    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
    c.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 treatment-related toxicities are present
    5.Subject has only localised advanced disease
    6.Documented serum albumin <3 g/dL within 7 days prior to randomisation
    7.Known history of central nervous system (CNS) metastases. (Subjects on a stable or decreasing dose of steroids and deemed clinically stable as per the investigator’s assessment are eligible)
    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 (note that subjects with hepatitis C who have been clinically cured, defined as persistent absence of hepatitis C ribonucleic acid (RNA) detected by polymerase chain reaction (PCR) test in serum 12 weeks after completing antiviral treatment, are eligible for this study)
    13.Active infection or an unexplained fever >38.5°C during screening visits or on the first scheduled day of dosing (at the discretion of the investigator, subjects with tumour fever may be enroled), 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 (please refer to Appendix 1). 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 (carcinoid, islet cell) or acinar pancreatic carcinoma
    19.Subjects who, in the opinion of the investigator, have symptoms or signs suggestive of clinically unacceptable deterioration of the primary disease at the time of screening
    20.History of systemic tissue disorders (e.g. lupus, scleroderma, arteritis nodosa)
    21.History of interstitial lung disease, history of slowly progressive dyspnoea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies
    22.History of peripheral artery disease (e.g. claudication, Leo Buerger's disease)
    23.Subjects who have received a live vaccine within 4 weeks prior to randomisation
    24.Please refer to Exclusion Criteria 24.
    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.
    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.
    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 nab-paclitaxel+gemcitabine. Investigator-assessed tumour response will be used in efficacy analysis.
    - Plasma concentrations of total irinotecan and SN-38 will be used to characterise corresponding PK parameters, in co-administration with 5-FU and oxaliplatin, using a nonlinear mixed effects approach. Individual PK parameters will be estimated if warranted by the data. Oxaliplatin and/or 5-FU concentrations might be used for further PK characterisation if more investigations are required.
    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.
    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.
    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
    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 No
    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
    Austria
    Belgium
    Brazil
    Canada
    Czech Republic
    France
    Germany
    Hungary
    Israel
    Italy
    Poland
    Portugal
    Russian Federation
    Spain
    United Kingdom
    United States
    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 565 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
    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 days
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months6
    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: 525
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 225
    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 state20
    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
    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 Decision2020-02-27
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-05-07
    P. End of Trial
    P.End of Trial StatusGB - no longer in EU/EEA
    For support, visit the EMA Service Desk , log in using your EMA account and open a ticket specifying "EU CTR" in your request.
    If you do not have an account, please visit the EMA Account management page page click on "Create an EMA account" and follow the instructions.
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2022 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA