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   41470   clinical trials with a EudraCT protocol, of which   6815   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) .
     
    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:2018-004004-19
    Sponsor's Protocol Code Number:QBGJ398-301
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2021-06-17
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2018-004004-19
    A.3Full title of the trial
    A Phase 3 Multicenter, Open-Label, Randomized, Controlled Study of Oral Infigratinib versus Gemcitabine with Cisplatin in Subjects with Advanced/Metastatic or Inoperable Cholangiocarcinoma with FGFR2 Gene Fusions/Translocations: The PROOF Trial
    Studio multicentrico di fase 3, in aperto, randomizzato,controllato con infigratinib orale rispetto a gemcitabina in combinazione con cisplatino in soggetti con colangiocarcinoma in stadio avanzato/metastatico o inoperabile con fusioni/traslocazioni del gene FGFR2: Sperimentazione PROOF
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    The PROOF Trial
    The PROOF Trial
    A.3.2Name or abbreviated title of the trial where available
    The PROOF Trial
    The PROOF Trial
    A.4.1Sponsor's protocol code numberQBGJ398-301
    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 SponsorQED Therapeutics 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 supportQED Therapeutics, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationPPD Global
    B.5.2Functional name of contact pointDerek Swartz
    B.5.3 Address:
    B.5.3.1Street Address3900 Paramount Parkway
    B.5.3.2Town/ cityMorrisville
    B.5.3.3Post codeNC 27560-7200
    B.5.3.4CountryUnited States
    B.5.4Telephone number0019196483421
    B.5.5Fax number000000000
    B.5.6E-mailderek.swartz@ppdi.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 No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameInfigratinib
    D.3.2Product code [BGJ398]
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNInfigratinib
    D.3.9.1CAS number 872511-34-7
    D.3.9.2Current sponsor codeBGJ398
    D.3.9.4EV Substance CodeSUB186757
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin 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 No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameInfigratinib
    D.3.2Product code [BGJ398]
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNINFIGRATINIB
    D.3.9.1CAS number 872511-34-7
    D.3.9.2Current sponsor codeBGJ398
    D.3.9.4EV Substance CodeSUB186757
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    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: 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.2.1.1.1Trade name GEMCI-cell®
    D.2.1.1.2Name of the Marketing Authorisation holderStada Pharm
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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 nameGEMCI-cell®
    D.3.2Product code [-]
    D.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous drip use (Noncurrent)
    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 number38
    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 GEMCI-cell®
    D.2.1.1.2Name of the Marketing Authorisation holderEG/Eurogenerics
    D.2.1.2Country which granted the Marketing AuthorisationBelgium
    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 nameGEMCI-cell®
    D.3.2Product code [-]
    D.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous drip use (Noncurrent)
    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.3.9.2Current sponsor code-
    D.3.9.4EV Substance CodeSUB07483MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number38
    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 Cisplatin TEVA®
    D.2.1.1.2Name of the Marketing Authorisation holderTEVA GmbH
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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 nameCisplatin
    D.3.2Product code [-]
    D.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous drip use (Noncurrent)
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCISPLATINO
    D.3.9.2Current sponsor codeCisplatin TEVA® 50mg/50mL
    D.3.9.4EV Substance CodeSUB07483MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1
    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.2.1.2Country which granted the Marketing AuthorisationNetherlands
    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 nameRenagel
    D.3.2Product code [-]
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNSEVELAMER
    D.3.9.2Current sponsor codeSevelamer
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number800
    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: 7
    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.2.1.2Country which granted the Marketing AuthorisationNetherlands
    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 nameSevelamer
    D.3.2Product code [-]
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNSEVELAMER
    D.3.9.2Current sponsor codeSevelamer
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number400
    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
    Cholangiocarcinoma
    Colangiocarcinoma
    E.1.1.1Medical condition in easily understood language
    Biliary tract malignancy
    Malignità del tratto biliare
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10008593
    E.1.2Term Cholangiocarcinoma
    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
    The primary objective is to determine if treatment with infigratinib improves progression-free survival (PFS) as assessed by blinded independent central review (BICR) compared to treatment with gemcitabine and cisplatin in subjects with unresectable locally advanced or metastatic cholangiocarcinoma with fibroblast growth factor receptor 2 (FGFR2) gene fusions/ translocations.
    L’obiettivo primario è determinare se il trattamento con infigratinib migliora la sopravvivenza libera da progressione (progression-free survival, [PFS]) valutata mediante revisione centrale indipendente in cieco (Blinded independent central review, BICR) rispetto al trattamento con gemcitabina e cisplatino in soggetti con colangiocarcinoma in stadio localmente avanzato o metastatico non resecabile con fusioni/traslocazioni del gene del recettore 2 del fattore di crescita dei fibroblasti (fibroblast growth factor receptor 2, [FGFR2]).
    E.2.2Secondary objectives of the trial
    •Determine if treatment with infigratinib improves overall survival (OS) compared to treatment with gemcitabine and cisplatin in subjects with unresectable locally advanced or metastatic cholangiocarcinoma with FGFR2 gene fusions/translocation
    •Evaluate the efficacy of infigratinib treatment compared to gemcitabine and cisplatin in terms of investigator assessed PFS.
    •Further evaluate the efficacy in subjects treated with infigratinib versus gemcitabine and cisplatin by overall response rate (ORR), best overall response (BOR), duration of response and disease control rate determined by BICR and by the investigator.
    •Characterize the safety and tolerability of single agent infigratinib.
    • Determinare se il trattamento con infigratinib migliora la sopravvivenza globale (overall survival, [OS]) rispetto al trattamento con gemcitabina e cisplatino nei soggetti con colangiocarcinoma in stadio localmente avanzato o metastatico non resecabile con fusioni/traslocazioni del gene FGFR2.
    •Valutare l’efficacia del trattamento con infigratinib rispetto a gemcitabina e cisplatino in termini di PFS valutata dallo sperimentatore.
    •Valutare ulteriormente l’efficacia in soggetti trattati con infigratinib rispetto a gemcitabina e cisplatino secondo il tasso di risposta complessiva (overall response rate, [ORR]), migliore risposta complessiva (best overall response, [BOR]), durata della risposta e tasso di controllo della malattia determinati mediante BICR e dallo sperimentatore.
    •Caratterizzare la sicurezza e la tollerabilità del singolo agente infigratinib.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Have histologically or cytologically confirmed unresectable locally advanced or metastatic cholangiocarcinoma. Subjects with gallbladder cancer or ampulla of Vater carcinoma are not eligible.
    2. Have written documentation of local laboratory or central laboratory determination of FGFR2 gene fusions/translocations from tumor tissue collected before treatment.
    3. Have an archival tissue sample available with sufficient tumor for central FGFR2 fusion/translocation molecular testing. However, if an archival tissue sample is not available, a newly obtained (before
    randomization) tumor biopsy may be submitted instead. If written documentation of FGFR2 fusion/translocation in tumor tissue is available from the central laboratory, an additional tumor sample does not need to
    be submitted for central FGFR2 fusion/translocation molecular testing.Note: All enrolled subject must have determination of FGFR2 gene fusions/translocations by the central laboratory as confirmation of local
    laboratory testing, but this central confirmation is not required prior toenrollment in the study.
    4. Have full recovery from the following permitted prior treatments (as applicable) such that the subject is reasonably expected to toleratestudy treatment (gemcitabine/cisplatin or infigratinib) according to the
    investigator's assessment:
    a. A non-curative operation (ie., R2 resection [with macroscopic residualdisease] or palliative bypass surgery only)
    b. Curative surgery with evidence of unresectable disease relapse requiring systemic chemotherapy
    c. Adjuvant radiotherapy (with or without radio-sensitizing low-dose chemotherapy) for localized disease provided there has been clear evidence of disease progression before inclusion in this study
    d. Adjuvant or neoadjuvant chemotherapy, provided recurrence afterdate of completion of therapy was = 6 months before trial entry
    e. Photodynamic treatment provided there is clear evidence of disease
    progression at the local site or at a new metastatic site.
    5. Are = 18 years of age of either gender.
    6. Have an Eastern Cooperative Oncology Group (ECOG) performance
    status = 1.
    7. Have a life expectancy > 3 months.
    8. Are able to read and/or understand the details of the study and provide written evidence of informed consent as approved by Institutional Review Board (IRB)/Independent Ethics Committee (IEC).
    9. Are able to swallow and retain oral medication.
    10. Are willing and able to comply with scheduled visits, treatment plan and laboratory tests.
    11. If a woman of childbearing potential (WOCBP), must have a negative pregnancy test within 7 days of the first dose of study drug. A woman is not of childbearing potential if she has undergone surgical
    sterilization (total hysterectomy, or bilateral tubal ligation or bilateral oophorectomy at least 6 weeks before taking study drug) or if she is postmenopausal and has had no menstrual bleeding of any kind including menstrual period, irregular bleeding, spotting, etc., for at least 12 months, with an appropriate clinical profile, and there is no other cause of amenorrhea (eg., hormonal therapy, prior chemotherapy).
    1. Essere affetti da un colangiocarcinoma istologicamente o citologicamente confermato non localmente avanzato o metastatico. I soggetti con tumore della colecisti o carcinoma dell’ampolla di Vater non sono idonei.
    2. Presentare documentazione scritta di un laboratorio locale o centrale della determinazione di fusioni/traslocazioni del gene FGFR2 dal tessuto tumorale prelevato prima del trattamento.
    3. Avere la disponibilità di un campione di tessuto di archivio contenente una quantità sufficiente di tessuto tumorale per l’analisi molecolare centrale di fusione/traslocazione del gene FGFR2. Tuttavia, se un campione di tessuto di archivio non è disponibile, al suo posto può essere presentata una nuova biopsia (precedente alla randomizzazione) del tessuto tumorale. Se è disponibile la documentazione scritta della fusione/traslocazione del gene FGFR2 nel tessuto tumorale da parte del laboratorio centrale, non è necessario presentare un altro campione tumorale per l’analisi molecolare centrale di fusione/traslocazione del gene FGFR2. Nota: tutti i soggetti arruolati devono essere sottoposti a determinazione delle fusioni/traslocazioni del gene FGFR2 da parte del laboratorio centrale come conferma dell’analisi del laboratorio locale, ma questa conferma centrale non è richiesta prima dell’arruolamento nello studio.
    4. Aver avuto un recupero completo dai seguenti trattamenti precedenti consentiti (se pertinente) in modo che si preveda ragionevolmente che il soggetto tolleri il trattamento dello studio (gemcitabina/cisplatino o infigratinib) secondo la valutazione dello sperimentatore:
    a. intervento non curativo (ovvero resezione R2 [con malattia macroscopica residua] o solo intervento di bypass palliativo)
    b. intervento chirurgico curativo con evidenza di recidiva non resecabile della malattia che richiede chemioterapia sistemica
    c. radioterapia adiuvante (con o senza chemioterapia radiosensibilizzante a basso dosaggio) per la malattia localizzata, a condizione che vi sia una chiara evidenza della progressione della malattia prima dell’inclusione in questo studio
    d. chemioterapia adiuvante o neoadiuvante, a condizione che la comparsa della recidiva si sia verificata =6 mesi dopo la data di completamento della terapia e prima dell’ingresso nella sperimentazione
    e. trattamento fotodinamico a condizione che vi sia una chiara evidenza di progressione della malattia nel sito localizzato o in un nuovo sito metastatico.
    5. Essere di età = 18 anni di entrambi i sessi.
    6. Presentare Eastern Cooperative Oncology Group (ECOG) performance status = 1.
    7. Avere un’aspettativa di vita > 3 mesi.
    8. Essere in grado di leggere e/o di comprendere i dettagli dello studio e di fornire evidenza scritta di consenso informato come approvato dall’Institutional Review Board (IRB)/Comitato Etico indipendente (CEI).
    9. Essere in grado di deglutire e trattenere il medicinale per uso orale.
    10. Essere disposti e in grado di rispettare le visite programmate, il programma terapeutico e gli esami di laboratorio.
    11. I soggetti di sesso femminile in età fertile (woman of childbearing potential, [WOCBP]) devono presentare un test di gravidanza con esito negativo 7 giorni prima della prima dose del farmaco dello studio. Una donna non è fertile se è stata sottoposta a sterilizzazione chirurgica (isterectomia totale o legatura bilaterale delle tube oppure ovariectomia bilaterale almeno 6 settimane prima di assumere il farmaco dello studio) o se è in postmenopausa e non ha avuto perdite mestruali di alcun tipo, inclusi ciclo mestruale, sanguinamento irregolare, spotting, ecc., per almeno 12 mesi, con un profilo clinico adeguato e senza alcuna altra causa dell’amenorrea (per es., terapia ormonale, precedente chemioterapia).
    E.4Principal exclusion criteria
    1.Have received treatment with any systemic anti-cancer therapy for unresectable locally, advanced or metastatic cholangiocarcinoma. Prior neoadjuvant or adjuvant therapy is permitted if documented disease
    recurrence occurred = 6 months after the last date of neoadjuvant or adjuvant therapy.
    2.Have history of a liver transplant.
    3 Have previously or currently is receiving treatment with a mitogenactivated protein kinase MEK or selective FGFR inhibitor.
    4.Have neurological symptoms related to underlying disease requiring increasing doses of corticosteroids. Note: Steroid use for management of central nervous system tumors is allowed but must be at a stable dose for at least 2 weeks preceding study entry.
    5.Have a history of another primary malignancy within 3 years exceptadequately treated in situ carcinoma of the cervix or non-melanoma carcinoma of the skin or any other curatively treated malignancy that is
    not expected to require treatment for recurrence during the course of the study.
    6.Have any other medical condition that would, in the investigator's judgment, prevent the subject's participation in the clinical study due to safety concerns or compliance with clinical study procedures.
    7.Have current evidence of corneal or retinal disorder/keratopathy including, but not limited to, bullous/band keratopathy, inflammation or ulceration, keratoconjunctivitis, confirmed by ophthalmic examination.
    Subjects with asymptomatic ophthalmic conditions assessed by the investigator to pose minimal risk for study participation may be enrolled in the study.
    8.Have a history and/or current evidence of extensive tissue calcification including, but not limited to, the soft tissue, kidneys,intestine, myocardium, vascular system and lung with the exception of calcified lymph nodes, minor pulmonary parenchymal calcifications, and asymptomatic coronary calcification.
    9.Have impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral infigratinib (eg., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption
    syndrome, small bowel resection).
    10.Have current evidence of endocrine alterations of calcium/phosphate homeostasis, eg., parathyroid disorders, history of parathyroidectomy, tumor lysis, tumoral calcinosis etc.
    11.Are currently receiving or are planning to receive during participation in this study, treatment with agents that are known strong inducers or inhibitors of CYP3A4 and medications which increase serum phosphorus and/or calcium concentration. Subjects are not permitted toreceive enzyme-inducing anti-epileptic drugs, including carbamazepine, phenytoin, phenobarbital, and primidone.
    12.Have consumed grapefruit, grapefruit juice, grapefruit hybrids, pomegranates, star fruits, pomelos, Seville oranges or products containing juice of these fruits within 7 days prior to first dose of study drug.
    13.Have used medications known to prolong the QT interval and/or are associated with a risk of Torsades de Pointes (TdP) 7 days prior to first dose of study drug.
    14.Have used amiodarone within 90 days prior to first dose of study drug.
    15. Have insufficient bone marrow function:
    a. Absolute neutrophil count (ANC) <1,000/mm3 (1.0 × 109/L)
    b. Platelets <100,000/mm3 (<100× 109/L)
    c. Hemoglobin <9.0 g/dL
    1. Aver ricevuto un trattamento con qualsiasi terapia antitumorale sistemica per colangiocarcinoma non resecabile, localmente avanzato o metastatico. Una precedente terapia neoadiuvante o adiuvante è consentita se la recidiva di malattia documentata si è verificata =6 mesi dopo l’ultima data della terapia neoadiuvante o adiuvante.
    2. Presentare un’anamnesi di un trapianto di fegato.
    3. Aver ricevuto un trattamento precedente o attuale con un inibitore di proteine chinasi attivate da mitogeno (mitogen-activated protein kinase, MEK) o un inibitore selettivo di FGFR.
    4. Manifestare sintomi neurologici correlati alla malattia sottostante che richiedono dosi crescenti di corticosteroidi. Nota: L’uso di steroidi per la gestione dei tumori del sistema nervoso centrale è consentito, ma deve avere un dosaggio stabile per almeno 2 settimane prima dell’ingresso nello studio.
    5. Presentare un’anamnesi di un’altra neoplasia maligna primaria nei 3 anni precedenti, ad eccezione di carcinoma del collo dell’utero in situ adeguatamente trattato oppure di carcinoma cutaneo non melanoma o di qualsiasi altro tumore maligno trattato con intento curativo che non si prevede possa richiedere un trattamento per la recidiva nel corso dello studio.
    6. Essere affetti da una qualsiasi altra patologia medica che, a giudizio dello sperimentatore, prevenga la partecipazione del soggetto allo studio clinico a causa di problemi di sicurezza o di conformità alle procedure dello studio clinico.
    7. Presentare un’attuale evidenza di disturbo corneale o retinico/cheratopatia, incluse, in modo non limitativo, cheratopatia bollosa/a banda, infiammazione o ulcerazione e cheratocongiuntivite confermate mediante esame oftalmologico. I soggetti con patologie oftalmiche asintomatiche valutate dallo sperimentatore come comportanti un rischio minimo per la partecipazione allo studio possono essere arruolati allo studio.
    8. Presentare un’anamnesi e/o un’attuale evidenza di estesa calcificazione dei tessuti, inclusi, in modo non limitativo, tessuti molli, reni, intestino, miocardio, sistema vascolare e polmone con l’eccezione di linfonodi calcificati, calcificazioni di lieve entità del parenchima polmonare e calcificazione coronarica asintomatica.
    9. Presentare un’insufficienza della funzione gastrointestinale (GI) o una malattia GI che possa alterare significativamente l’assorbimento orale di infigratinib (per es., malattie ulcerose, nausea, vomito e diarrea non controllati, sindrome da malassorbimento, resezione dell’intestino tenue).
    10. Presentare un’evidenza attuale di alterazioni endocrine dell’omeostasi del calcio/fosfato, per es., patologie delle paratiroidi, anamnesi di paratiroidectomia, lisi tumorale, calcinosi tumorale, ecc.
    11. Essere attualmente sottoposti, o prevedere di essere sottoposti, durante la partecipazione a questo studio, a un trattamento con agenti che sono noti per essere forti induttori o inibitori di CYP3A4 e medicinali che aumentano la concentrazione sierica di fosforo e/o di calcio. I soggetti non sono autorizzati a ricevere farmaci antiepilettici induttori enzimatici, inclusi carbamazepina, fenitoina, fenobarbital e primidone. Vedere Appendice 2 (Sezione 17.2) per i dettagli.
    12. Aver consumato pompelmo, succo di pompelmo, ibridi di pompelmo, melograno, frutti di carambola, pomeli, arance amare o prodotti a base di succhi di questi frutti nei 7 giorni precedenti la prima dose del farmaco dello studio.
    13. Aver assunto medicinali noti per prolungare l’intervallo QT e/o che siano associati a un rischio di Torsade de pointes (TdP) nei 7 giorni precedenti la prima dose del farmaco dello studio.
    14. Aver assunto amiodarone nei 90 giorni precedenti la prima dose del farmaco dello studio.
    15. Presentare un’insufficiente funzionalità del midollo osseo:
    a. conta assoluta dei neutrofili (Absolute neutrophil count, [ANC]) < 1.000/mm3 (1.0 × 109/l)
    b. piastrine < 100.000/mm3 (< 100 ×109/l)
    c. emoglobina < 9,0 g/dl
    E.5 End points
    E.5.1Primary end point(s)
    Progression-free survival (from date of randomization until date of progression as determined by BICR or death due to any cause).
    PFS (dalla data di randomizzazione fino alla data di progressione determinata mediante BICR o dal decesso per qualsiasi causa)
    E.5.1.1Timepoint(s) of evaluation of this end point
    From date of randomization until date of progression as determined by BICR or death due to any cause.
    Dalla data di randomizzazione alla data di progressione determinata mediante valutazione centrale indipendente (BICR) o decesso per qualsiasi causa
    E.5.2Secondary end point(s)
    1. Overall survival (from date of randomization until date of death).
    2. Progression-free survival (PFS) as determined by the investigator.
    3. Overall response rate (ORR) assessed by BICR according to Response Evaluation Criteria in Solid Tumors (RECIST)
    Version 1.1.
    4. ORR assessed by the investigator according to RECIST Version 1.1.
    5. Best overall response (BOR), disease control rate (partial response [PR] + complete response [CR] + stable disease [SD]), and duration of response (only for subjects who have a response) assessed by BICR and by the investigator according to RECIST 1.1.
    6. Type, frequency, and severity of adverse events (AEs) and serious AEs (SAEs), laboratory abnormalities, and other safety findings.
    1.OS (dalla data di randomizzazione fino alla data di decesso)
    2.PFS come determinata dallo sperimentatore
    3. ORR valutato mediante BICR secondo i Criteri di valutazione della risposta nei tumori solidi (Response Evaluation Criteria in Solid Tumors, [RECIST]) Versione 1.1
    4.ORR valutato dallo sperimentatore secondo i criteri RECIST Versione 1.1
    5.BOR, tasso di controllo della malattia (risposta parziale (partial response, [PR]) + risposta completa (complete response, [CR]) + malattia stabile (stable disease, [SD])) e durata della
    risposta (solo per i soggetti che hanno una risposta) valutati mediante BICR e dallo sperimentatore secondo i criteri RECIST 1.1
    6. Tipo, frequenza e gravità di eventi avversi (EA) ed eventi avversi seri (serious adverse event, [SAE]), di anomalie di laboratorio e di altri risultati di sicurezza
    E.5.2.1Timepoint(s) of evaluation of this end point
    1. From date of randomization until date of death every 3 months; every 3 months after disease progression
    2. Every 8 weeks
    3. Every 8 weeks
    4. Every 8 weeks
    5. Every 8 weeks
    6. From randomization until 30 days after the last dose of study drug
    1. Ogni 3 mesi dalla data di randomizzazione alla data di decesso; ogni 3 mesi dopo la progressione della malattia
    2. Ogni 8 settimane
    3. Ogni 8 settimane
    4. Ogni 8 settimane
    5. Ogni 8 settimane
    6. Dalla randomizzazione fino a 30 giorni dopo l’ultima dose di farmaco dello studio
    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 No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Assessment of Biomarkers and genetic mutation
    Valutazione dei biomarcatori e mutazione genetica
    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) No
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    Gemcitabina and Cisplatino
    Gemcitabine and Cisplatin
    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 concerned7
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA48
    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
    Belgium
    Canada
    China
    France
    Germany
    Hungary
    Italy
    Korea, Republic of
    Spain
    Taiwan
    Thailand
    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 end of trial (study) is defined as the time when at least 274 OS events have been reached (for the primary OS analysis) and the last study subject has completed study treatment
    La fine della sperimentazione e' definita comedefinita come il momento in cui vengono raggiunti almeno 274 eventi di OS (per l’analisi di OS primaria) e l’ultimo soggetto ha completato il trattamento dello studio.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years5
    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 years5
    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: 191
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 193
    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 state24
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 100
    F.4.2.2In the whole clinical trial 384
    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)
    Best standard of care at investigator’s discretion
    Migliore cura standard a discrezione dello sperimentatore
    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 Decision2020-03-12
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-01-24
    P. End of Trial
    P.End of Trial StatusOngoing
    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