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    Summary
    EudraCT Number:2011-004687-30
    Sponsor's Protocol Code Number:MM-398-07-03-01
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2012-03-30
    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 number2011-004687-30
    A.3Full title of the trial
    NAPOLI 1: A Randomized, Open Label Phase 3 Study of MM-398, with or without 5-Fluorouracil and Leucovorin, versus 5-Fluorouracil and
    Leucovorin, in Patients with Metastatic Pancreatic Cancer Who have Failed Prior Gemcitabine-based Therapy
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study of MM-398 with or without 5-Fluorouracil and Leucovorin
    compared with 5- Fluorouracil and Leucovorin in Patients with advanced
    pancreatic cancer who were previously treated unsuccessfully with a
    gemcitabine-based therapy.
    A.3.2Name or abbreviated title of the trial where available
    NAPOLI 1
    A.4.1Sponsor's protocol code numberMM-398-07-03-01
    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 SponsorMerrimack Pharmaceuticals 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 supportMerrimack Pharmaceuticals
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMERRIMACK PHARMACEUTICALS, INC
    B.5.2Functional name of contact pointMerrimack MM398 Clinical Trial Mger
    B.5.3 Address:
    B.5.3.1Street AddressOne Kendall Square, Suite B7201
    B.5.3.2Town/ cityCambridge,
    B.5.3.3Post codeMA 02139
    B.5.3.4CountryUnited States
    B.5.4Telephone number001617441-1000
    B.5.5Fax number001617812-7776
    B.5.6E-mailclinical@merrimackpharma.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 No
    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 nameNanoliposomal Irinotecan
    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 Hydrochloride
    D.3.9.1CAS number 136572-09-3
    D.3.9.3Other descriptive nameNanoliposomal Irinotecan
    D.3.9.4EV Substance CodeSUB02772MIG
    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: 2
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    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 injection/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: 3
    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.2.5The 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 injection/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 INNCalcium folinate
    D.3.9.1CAS number 58-05-9
    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 number10
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Metastatic Pancreatic Cancer
    E.1.1.1Medical condition in easily understood language
    cancer of the pancreas that has spread to other areas
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level PT
    E.1.2Classification code 10033610
    E.1.2Term Pancreatic carcinoma 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 14.1
    E.1.2Level LLT
    E.1.2Classification code 10033599
    E.1.2Term Pancreatic adenocarcinoma 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 14.1
    E.1.2Level LLT
    E.1.2Classification code 10033605
    E.1.2Term Pancreatic 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 Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To compare overall survival following treatment with MM-398, with
    orwithout 5-fluorouracil and leucovorin,versus 5-fluorouracil and
    leucovorin in patients with metastatic pancreatic cancer that have
    progressed on gemcitabine based therapy.
    E.2.2Secondary objectives of the trial
    • To compare the following time-to-event efficacy
    endpoints between the two treatment arms:
    Progression-free survival (PFS)
    Time to treatment failure (TTF)
    • To compare the Objective Response Rate (ORR) between the two
    treatment arms
    • To compare the tumor marker response of CA 19-9 between the
    two treatment arms
    • To compare the Clinical Benefit Response (CBR) rate between
    the two treatment arms
    • To assess patient-reported outcomes (PROs) between the two
    treatment arms using the European Organization for Research and
    Treatment of Cancer (EORTC) quality-of-life core questionnaire
    (EORTC-QLQ-C30)
    • To compare the safety and adverse event profile between
    the two treatment arms
    •To determine the pharmacokinetic properties of MM-398, as a single agent and in combination with 5-FU and leucovorin, in this
    population
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Translational Research Companion Protocol for NAPOLI-1: A
    Randomized, Open Label Phase 3 Study of MM-398, with or without 5-Fluorouracil and Leucovorin, versus 5- Fluorouracil and
    Leucovorin, in Patients with Metastatic Pancreatic Cancer Who have
    Failed Prior Gemcitabine-based Therapy
    E.3Principal inclusion criteria
    • Histologically or cytologically confirmed adenocarcinoma of
    exocrine pancreas
    • Documented metastatic disease; disease status may be measurable or non-measurable as defined by RECIST v1.1 guidelines
    • Documented disease progression after prior gemcitabine or
    gemcitabine containing therapy, in locally advanced or metastatic
    setting. Examples of permitted therapies include, but are not limited to:
    o Single agent gemcitabine
    o Any one gemcitabine-based regimen, with or without
    maintenance gemcitabine
    o Single agent gemcitabine to which a platinum agent, a
    fluoropyrimidine, or erlotinib was subsequently added
    o Gemcitabine administered in the adjuvant setting if disease
    recurrence occurred within 6 months of completing the
    adjuvant therapy
    • KPS > 70
    • Adequate bone marrow reserves as evidenced by:
    o ANC > 1,500 cells/μl without the use of hematopoietic growth
    factors; and
    o Platelet count > 100,000 cells/μl; and
    o Hemoglobin > 9 g/dL
    • Adequate hepatic function as evidenced by:
    o Serum total bilirubin within normal range for the institution
    (biliary drainage is allowed for biliary obstruction)
    o Albumin levels ≥ 3.0 g/dL
    o Aspartate aminotransferase (AST) and alanine
    aminotransferase (ALT) ≤ 2.5 x ULN (≤ 5 x ULN is acceptable
    if liver metastases are present)
    • Adequate renal function as evidenced by a serum creatinine ≤1.5
    x ULN
    • Normal ECG or ECG without any clinically significant findings
    • Recovered from the effects of any prior surgery, radiotherapy or
    other anti-neoplastic therapy
    • At least 18 years of age
    • Able to understand and sign an informed consent (or have a legal
    representative who is able to do so)
    E.4Principal exclusion criteria
    • Active CNS metastases (indicated by clinical symptoms, cerebral
    edema, steroid requirement, or progressive disease) patients should have been off steroids for at least 28 days prior to starting study therapy
    • Clinically significant gastrointestinal disorder including hepatic
    disorders, bleeding, inflammation, occlusion, or diarrhea > grade 1
    • History of any second malignancy in the last 5 years; subjects with prior history of in-situ cancer or basal or squamous cell skin cancer are eligible. Subjects with other malignancies are eligible if they have been continuously disease free for at least 5 years.
    • Severe arterial thromboembolic events (myocardial infarction,
    unstable angina pectoris, stroke) less than 6 months before inclusion
    • NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure
    • 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, patients with tumor fever may be enrolled), which in the investigator's opinion might compromise the patient's participation in the trial or affect the study outcome
    • Known hypersensitivity to any of the components of MM-398, other liposomal products, fluropyrimidines or leucovorin
    • Investigational therapy administered within 4 weeks, or within a time interval less than at least 5 half lives of the investigational agent, whichever is longer, prior to the first scheduled day of dosing in this study
    • Any other medical or social condition deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results
    • Pregnant or breast feeding; females of child-bearing potential must test negative for pregnancy at the time of enrollment based on a urine or serum pregnancy test. Both male and female patients ofreproductive potential must agree to use a reliable method of birth control, during the study and for 3 months following the last dose of study drug.
    E.5 End points
    E.5.1Primary end point(s)
    Overall survival (OS)
    E.5.1.1Timepoint(s) of evaluation of this end point
    The analysis for primary endpoint will take place once at least 305 death events have occurred.
    E.5.2Secondary end point(s)
    Progression Free Survival
    Time to treatment failure
    Objective Response Rate
    Clinical Benefit Response
    Tumor Marker Response
    Patient Reported Outcome
    E.5.2.1Timepoint(s) of evaluation of this end point
    On-going
    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 No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) 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 No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial3
    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 concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA33
    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
    Argentina
    Australia
    Brazil
    Canada
    Czech Republic
    France
    Germany
    Hungary
    India
    Italy
    Korea, Republic of
    Russian Federation
    South Africa
    Spain
    Taiwan
    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
    As per protocol
    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 months0
    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 months0
    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: 150
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 255
    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 state16
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 150
    F.4.2.2In the whole clinical trial 405
    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)
    As per protocol
    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 Decision2012-03-19
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2012-05-09
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2015-11-06
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