Flag of the European Union EU Clinical Trials Register Help

Clinical trials

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

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


    The EU Clinical Trials Register currently displays   44293   clinical trials with a EudraCT protocol, of which   7351   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2016-004340-11
    Sponsor's Protocol Code Number:BAY1163877/17403
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2019-09-13
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2016-004340-11
    A.3Full title of the trial
    A randomized, open label, multicenter Phase 2/3 study to evaluate the efficacy and safety of rogaratinib (BAY 1163877) compared to
    chemotherapy in patients with FGFR-positive locally advanced or metastatic urothelial carcinoma who have received prior platinum containing chemotherapy
    Studio randomizzato, multicentrico, in aperto, di fase 2/3 volto alla valutazione dell’efficacia e della sicurezza di rogaratinib (BAY 1163877) rispetto alla chemioterapia in pazienti con carcinoma uroteliale localmente avanzato o metastatico, positivo per FGFR, sottoposti in precedenza a chemioterapia contenente platino
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Phase 2/3 study of rogaratinib (pan FGFR inhibitor) vs chemotherapy in patients with locally advanced or metastatic urothelial carcinoma with a high amount of specific cell growth factor receptors 1 and 3 (FGFR1 and 3) in the tumor cells
    Studio di fase 2/3 su rogaratinib (BAY 1163877) rispetto alla chemioterapia in pazienti con carcinoma uroteliale localmente avanzato o metastatico, positivo per FGFR
    A.3.2Name or abbreviated title of the trial where available
    n.a.
    n.a.
    A.4.1Sponsor's protocol code numberBAY1163877/17403
    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 SponsorBAYER HEALTHCARE AG
    B.1.3.4CountryGermany
    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 supportBayer AG
    B.4.2CountryGermany
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationBayer AG
    B.5.2Functional name of contact pointBayer Clinical Trials Contact
    B.5.3 Address:
    B.5.3.1Street AddressCPT Team / Ref: "EU CTR"/ Bayer AG
    B.5.3.2Town/ cityBerlino
    B.5.3.3Post code13342
    B.5.3.4CountryGermany
    B.5.4Telephone number0
    B.5.5Fax number0
    B.5.6E-mailclinical-trials-contact@bayer.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 nameBAY 1163877 hydrochloride coated tablet 200 mg
    D.3.2Product code BAY 1163877 hydrochloride coat
    D.3.4Pharmaceutical form Coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMP
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNROGARATINIB
    D.3.9.2Current sponsor codeBAY 1213802 hydrate
    D.3.9.3Other descriptive nameBAY 1163877 hydrochloride hydrate
    D.3.9.4EV Substance CodeSUB188629
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number200
    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 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 Docetaxel cell pharm
    D.2.1.1.2Name of the Marketing Authorisation holdercell pharm 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.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMP
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNDOCETAXEL
    D.3.9.1CAS number 114977-28-5
    D.3.9.2Current sponsor code0000
    D.3.9.4EV Substance CodeSUB12492MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.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 Paclitaxel Aurobindo
    D.2.1.1.2Name of the Marketing Authorisation holderPUREN Pharma GmbH & Co. KG
    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.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMP
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPACLITAXEL
    D.3.9.1CAS number 33069-62-4
    D.3.9.2Current sponsor code0000
    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 number6
    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 Javlor
    D.2.1.1.2Name of the Marketing Authorisation holderPierre Fabre Médicament
    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 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 IMP
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNVINFLUNINE
    D.3.9.1CAS number 162652-95-1
    D.3.9.2Current sponsor code00000
    D.3.9.4EV Substance CodeSUB00063MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    D.3.11 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
    mRNA FGF receptor 1 and 3 positive locally advanced or metastatic urothelial carcinoma progressed after prior platinum-containing chemotherapy
    Positivo mRNA FGF recettori 1 e 3 localmente avanzato o metastatico, con carcinoma uroteliale in progressione sottoposti in precedenza a chemioterapia contenente platino
    E.1.1.1Medical condition in easily understood language
    Locally advanced or metastatic bladder cancer with a high amount of specific cell growth factor receptors 1 and 3 (FGFR1 and 3) in the tumor cells
    Localmente avanzato o metastatico carcinoma uroteliale con quantità elevate di recettore cellulare del fattore di crescita recettore 1 e 3 (FGFR 1 e 3) nelle cellule tumorali
    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 LLT
    E.1.2Classification code 10064467
    E.1.2Term Urothelial carcinoma
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Primary objective of this trial is to demonstrate the superiority of rogaratinib over chemotherapy in
    terms of prolonging overall survival of urothelial carcinoma patients with FGFR positive tumors.
    The objective for the Phase 2 part of the study is to demonstrate the efficacy of rogaratinib over chemotherapy in terms of objective response rate of urothelial carcinoma patients with FGFR positive tumors.
    Obiettivo primario: Dimostrare la superiorità di rogaratinib rispetto alla chemioterapia in termini di prolungamento della sopravvivenza globale dei pazienti affetti da carcinoma uroteliale con tumori positivi per FGFR.
    L’obiettivo della Fase 2 dello studio è dimostrare l’efficacia di rogaratinib rispetto alla chemioterapia in termini di tasso di risposta obiettiva dei pazienti affetti da carcinoma uroteliale con tumori positivi per FGFR.
    E.2.2Secondary objectives of the trial
    Secondary objective of this trial is to evaluate additional efficacy including the following variables:
    Progression-free survival (PFS)
    Objective response rate (ORR)
    Disease control rate (DCR)
    Duration of response (DOR)
    and to evaluate the safety of rogaratinib (adverse events)
    Tertiary objectives are:
    Patient-reported outcome (PRO)
    Evaluate biomarkers to investigate the drug (i.e. mode-of-action related)
    Pharmacokinetics
    effect and/or safety) and/or the pathomechanism of the disease.
    Pharmacokinetics
    Obiettivi secondari:
    • Valutare l’efficacia aggiuntiva, comprensiva delle seguenti variabili:
    o sopravvivenza libera da progressione (PFS)
    o tasso di risposta obiettiva (ORR)
    o tasso di controllo della malattia (DCR)
    o durata della risposta (DOR)
    • Valutare la sicurezza di rogaratinib (eventi avversi)
    Obiettivi terziari:
    • Esiti riferiti dai pazienti (PRO)
    • Valutazione dei biomarcatori per analizzare il farmaco (effetto e/o sicurezza correlati al meccanismo d’azione) e/o il meccanismo patologico della malattia
    • Profilo farmacocinetico
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Existence of archival or fresh biopsy for FGFR testing.
    FGFR testing of patients will be performed at the investigators' discretion up to a max. of 90 days prior to start of screening (signing of informed consent for study treatment eligibility). Investigators should ensure all patients will be eligible in terms of disease status and lines of treatment within this timeframe. If the patient is positive for FGFR 1
    and/or 3 and is unable start screening by 90 days after FGFR testing, the patient may still be considered for screening after discussion with the
    sponsor's designated medical representative and approval by the sponsor
    Male or female patients ≥ 18 years of age (at least age of legal
    maturity).
    Documented urothelial carcinoma (transitional cell carcinoma) including urinary bladder, renal pelvis, ureters, urethra, meeting all of the following criteria:
    Histologically or cytologically confirmed. Patients with mixed histologies are required to have a dominant transitional cell pattern.
    Locally advanced (T4b, any N; or any T, N 2−3) or metastatic disease (any T, any N and M1).
    Locally advanced bladder cancer must be unresectable i.e. invading the pelvic or abdominal wall (stage T4b) or presenting with bulky nodal
    disease (N2-3).
    ECOG Performance Status of 0 or 1.
    Disease progression during or following treatment with at least one platinum-containing regimen (patients should have been treated for at
    least 2 cycles). In patients who received prior adjuvant/neoadjuvant platinum-containing chemotherapy, progression had to occur within 12
    months of treatment.
    High FGFR1 or 3 mRNA expression levels (RNAscope score of 3+ or 4+; measurement is part of this protocol) in archival or fresh tumor biopsy
    specimen.
    At least 1 measurable lesion according to Response Evaluation Criteria in
    Solid Tumors (RECIST v.1.1) in contrast enhanced (unless contraindicated) CT or MRI.
    Adequate laboratory and organ function:
    Absolute neutrophil count (ANC) ≥ 1,500/mm3
    Platelet count ≥ 100,000/mm3
    Hemoglobin ≥ 9.0 g/dL (without transfusion or erythropoietin within 4
    weeks before randomization).
    Total bilirubin ≤ 1.5 times the upper limit of normal (ULN). Known
    Gilbert syndrome is allowed if total bilirubin is ≤ 3 x ULN.
    Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤
    2.5 x ULN (≤ 5 x ULN for patients with liver involvement of their cancer).
    Alkaline phosphatase limit ≤ 2.5 x ULN (≤ 5 x ULN for patients with liver
    and bone involvement of their cancer).
    Lipase < 2 x ULN
    Glomerular filtration rate (GFR) ≥ 30 mL/min/1.73 m2 according to
    Modification of Diet in Renal Disease (MDRD) abbreviated formula.
    International normalized ratio (INR) ≤ 1.5  ULN, and partial
    thromboplastin time (PTT) or activated PTT (aPTT) ≤ 1.5  ULN. Patients
    being treated with anticoagulant, e.g. warfarin or heparin, will be
    allowed to participate provided no prior evidence of an underlying
    abnormality in these parameters exists. Close monitoring of at least
    weekly evaluations will be performed until INR is stable based on a predose
    measurement as defined by the local standard of care.
    Women of childbearing potential (WOCBP) and fertile men must agree to
    use adequate contraception when sexually active from signing of the ICF
    for study treatment eligibility until at least 12 weeks after the last study
    drug administration. The investigator or a designated associate is
    requested to advise the patient how to achieve highly effective birth
    control. Highly effective (failure rate of less than 1% per year)
    contraception methods include:
    Combined (estrogen and progesterone containing: oral, intravaginal,
    transdermal) and progesterone-only (oral, injectable, implantable)
    hormonal contraception associated with inhibition of ovulation.
    Intrauterine device (IUD) or intrauterine hormone-releasing system
    (IUS).
    Bilateral tubal occlusion or vasectomized partner (provided that partner
    is the sole sexual partner and has received medical assessment of the
    surgical success).
    Sexual abstinence (reliability to be evaluated in relation to the duration
    of the clinical trial and the preferred and usual lifestyle of the patient).
    Periodic abstinence (e.g., calendar, ovulation, symptothermal, or
    postovulation methods) and withdrawal are not acceptable methods of
    contraception.
    Male patients with a female partner of childbearing potential must use a
    condom and ensure that an additional form of contraception is also used
    during treatment and until 12 weeks after last study drug
    administration.
    Negative serum pregnancy test in women of childbearing potential
    (performed within 7 days before randomization). Negative results must
    be available prior to study drug administration.
    • Disponibilità di un campione bioptico da archivio o appena prelevato per l’analisi dell’FGFR
    • L’analisi dell’FGFR sarà eseguita sui pazienti a discrezione degli sperimentatori al massimo 90 giorni prima dell’inizio dello screening. In questo periodo di tempo gli sperimentatori dovranno accertarsi che tutti i pazienti siano idonei in termini di stato della malattia e linee di trattamento.
    • Pazienti di sesso maschile o femminile di età ≥ 18 anni
    • Carcinoma uroteliale documentato (carcinoma a cellule transizionali), inclusi tumori alla vescica urinaria, pelvi renale, ureteri e uretra, che soddisfi tutti i seguenti criteri
    o Confermato istologicamente o citologicamente
    I pazienti con istologie miste devono presentare un pattern a cellule transizionali dominante.
    o Patologia localmente avanzata (T4b, qualsiasi N; o qualsiasi T, N 2−3) o metastatica (qualsiasi T, qualsiasi N e M1).
    Il cancro della vescica localmente avanzato deve essere non resecabile, ossia aver invaso la parete pelvica o addominale (stadio T4b) o presentare un interessamento linfonodale bulky (N2-3).
    • Performance status secondo ECOG pari a 0 o 1
    • Progressione della patologia durante o in seguito al trattamento con almeno un regime contenente platino (i pazienti devono essere stati trattati per almeno 2 cicli). Nei pazienti precedentemente trattati con chemioterapia adiuvante/neoadiuvante contenente platino, la progressione deve essersi verificata entro 12 mesi di trattamento.
    • Livelli elevati di espressione mRNA di FGFR1 o 3 (punteggio RNAscope di 3+ o 4+; la misurazione fa parte di questo protocollo) in un campione tumorale bioptico da archivio o appena prelevato
    • Almeno 1 lesione misurabile in base ai criteri Response Evaluation Criteria in Solid Tumors (RECIST v.1.1) evidenziata ad una TC o una RM con mezzo di contrasto (se non controindicata)
    Per l’elenco completo dei criteri di inclusione e di esclusione, consultare i paragrafi 6.1 e 6.2 del presente protocollo.
    E.4Principal exclusion criteria
    Previous or concurrent cancer except:
    cervical carcinoma in situ
    treated basal-cell or squamous cell skin carcinoma
    any cancer curatively treated > 3 years before randomization
    ocuratively treated incidental prostate cancer (T1/T2a)
    Symptomatic metastatic brain or meningeal tumors unless the patient is
    > 6 months from definitive therapy, has no radiological evidence of tumor growth and is clinically stable with respect to the tumor at
    randomization. Also the patient must not be undergoing acute steroid
    therapy or taper (chronic steroid therapy is acceptable provided that the
    dose is stable for one month prior to and following screening
    radiographic studies).
    Known human immunodeficiency virus (HIV) infection.
    Renal dialysis.
    Any malabsorption condition.
    Breast-feeding.
    Ongoing or previous treatment with anti-FGFR directed therapies (e.g.
    receptor tyrosine kinase inhibitors including rogaratinib or FGFR-specific
    antibodies) or with taxanes or vinflunine.
    More than two prior lines of systemic anti-cancer therapy for urothelial
    carcinoma.
    Ongoing or previous anti-cancer treatment within 4 weeks before
    randomization:
    Patients who have received prior treatment with anti-CTLA-4 may be
    enrolled provided at least 5 half-lives (approximately 75 days) have
    elapsed before randomization.
    Prior cancer vaccines and cellular immunotherapy are permitted.
    Previous radiotherapy is acceptable under the following conditions:
    Therapeutic radiotherapy ≥ 3 weeks before the baseline tumor scan.
    Palliative radiotherapy for bone metastases or soft tissue lesions is
    allowed and should be completed >7 days prior to baseline tumor scan.
    Lesions at the site of previous radiotherapy should have evidence of
    progressive disease if this is the only site of disease.
    Anti-cancer therapy is defined as any agent or combination of agents
    with clinically proven anti-tumor activity administered by any route with
    the purpose of affecting the malignancy, either directly or indirectly,
    including palliative and therapeutic endpoints.
    Use of strong inhibitors and inducers of CYP3A4 (see Appendix 16.1)
    should have been stopped 2 weeks before randomization.
    Concomitant therapies that are known to increase serum calcium or
    phosphate levels and cannot be discontinued or switched to a different
    medication before randomization.
    Substance abuse, medical, psychological or social conditions that may
    interfere with the patient's participation in the study or evaluation of the
    study results.
    Major surgery, or significant trauma within 4 weeks before
    randomization (central line surgery is not considered major surgery).
    Unresolved toxicity higher than National Cancer Institute's Common
    Terminology Criteria for Adverse Events, version 4.03 (CTCAE v.4.03)
    Grade 1 attributed to any prior therapy/procedure excluding alopecia,
    anemia and/or hypothyroidism.
    History or current condition of an uncontrolled cardiovascular disease
    including any of the following conditions:
    Congestive heart failure (CHF) NYHA > Class 2.
    Unstable angina (symptoms of angina at rest) or new-onset angina
    (within last 3 months before randomization).
    Myocardial infarction (MI) within past 6 months before randomization.
    Unstable cardiac arrhythmias requiring anti-arrhythmic therapy. Patients
    with arrhythmia under control with anti-arrhythmic therapy such as
    beta-blockers or digoxin are eligible.
    Arterial or venous thrombotic events or embolic events such as
    cerebrovascular accident (including transient ischemic attacks), deep
    vein thrombosis or pulmonary embolism within 3 months before
    randomization.
    Current evidence of endocrine alteration of calcium phosphate
    homeostasis (e.g. parathyroid disorder, history of parathyroidectomy,
    tumor lysis, tumoral calcinosis, paraneoplastic hypercalcemia).
    Current diagnosis of any retinal detachment, retinal pigment epithelial
    detachment (RPED), serous retinopathy or retinal vein occlusion.
    Active infection with hepatitis B or C, requiring treatment
    Active infections (≥ CTCAE v.4.03 Grade 3)
    Evidence or history of bleeding diathesis or coagulopathy
    Any hemorrhage / bleeding event ≥ CTCAE v.4.03 Grade 3 within 4
    weeks before randomization.
    Seizure disorder requiring therapy
    Serious, non-healing wound, ulcer or bone fracture
    Any condition that is unstable or could jeopardize the safety of the
    patient and his/her compliance in the study.
    Inability to swallow oral medications.
    Known hypersensitivity to any of the study drugs, study drug classes, or
    excipients in the formulation.
    Previous assignment to study treatment during this study.
    Investigational drug treatment outside of this study during or within 4 weeks before randomization.
    Close affiliation with the investigational site; e.g. a close relative of the investigator, dependent person (e.g. employee or student of the investigational site).
    • Tumore pregresso o concomitante, ad eccezione di
    o carcinoma cervicale in situ
    o carcinoma cutaneo basocellulare o squamocellulare trattato
    o qualsiasi tumore trattato con finalità terapeutiche > 3 anni prima della randomizzazione
    o carcinoma prostatico incidentale trattato con finalità terapeutiche (T1/T2a)
    • Trattamento antitumorale in corso o pregresso nelle 4 settimane precedenti la randomizzazione.
    • Più di due linee precedenti di terapia antitumorale sistemica per il carcinoma uroteliale
    • Trattamento in corso o pregresso con terapie mirate anti-FGFR (ad esempio inibitori dei recettori tirosin-chinasi, incluso rogaratinib, o anticorpi specifici per FGFR) oppure con taxani o vinflunina
    • Tossicità non risolta superiore al grado 1 secondo i criteri Common Terminology Criteria for Adverse Events del National Cancer Institute, versione 4.03 (CTCAE v.4.03), imputata a una terapia/procedura precedente, ad esclusione di alopecia, anemia e/o ipotiroidismo
    • Anamnesi o attuale presenza di malattie cardiovascolari non controllate, incluse le seguenti condizioni:
    o Insufficienza cardiaca congestizia (ICC) Classe NYHA > 2
    o Angina instabile (sintomi di angina a riposo) o angina di nuova insorgenza (nei 3 mesi precedenti la randomizzazione)
    o Infarto del miocardio (MI) nei 6 mesi precedenti la randomizzazione
    o Aritmie cardiache instabili che richiedono una terapia antiaritmica. I pazienti affetti da aritmia controllata con una terapia antiaritmica, ad esempio con betabloccanti o digossina, sono eleggibili.
    • Eventi trombotici o embolici arteriosi o venosi, quali accidente cerebrovascolare (inclusi attacchi ischemici transitori), trombosi venosa profonda o embolia polmonare nei 3 mesi precedenti la randomizzazione
    • Attuale evidenza di un’alterazione endocrina dell’omeostasi del calcio e del fosfato (ad esempio disturbo delle paratiroidi, anamnesi di paratiroidectomia, lisi tumorale, calcinosi tumorale, ipercalcemia paraneoplastica)
    • Qualsiasi emorragia/sanguinamento di Grado CTCAE v.4.03 ≥ 3 nelle 4 settimane precedenti alla randomizzazione
    • Attuale diagnosi di distacco della retina, distacco dell’epitelio pigmentato retinico (RPED), retinopatia sierosa o occlusione venosa retinica
    Per l’elenco completo dei criteri di inclusione e di esclusione, consultare i paragrafi 6.1 e 6.2 del presente protocollo.
    E.5 End points
    E.5.1Primary end point(s)
    Overall survival is the primary efficacy variable.
    The primary efficacy variable is overall survival (OS). OS data will be considered mature and the final OS analysis (i.e. primary completion)
    will be performed when approximately a total of 232 PIK3CA and RAS
    WT patients have died, in accordance with the power calculations
    specified for the full analysis set (FAS). For the primary efficacy variable
    of overall survival, a hierarchical fixed-sequence procedure based on
    stratified log-rank test controlling type I error at a level of 0.025 (onesided)
    will be conducted for the WT population first (step 1). A full alpha
    of 0.025 (one-sided) will be passed on to OS in all study population and
    some selected secondary endpoints (step 2), if and only if the null
    hypothesis of OS for WT population is rejected.in the following
    sequence: step 1) WT population; step 2) all study population. Step 2
    will be tested if and only if the null hypothesis of step 1) is rejected.
    Details on controlling family-wise type I error within step 2 for OS in all
    study population and selected secondary endpoints will be specified in
    the Statistical Analysis Plan (SAP).
    In addition, the hazard ratio (rogaratinib / chemotherapy) for OS and its
    95% confidence interval will be calculated using the Cox model,
    stratified by the same factors used for randomization, for both PIK3CA
    and/or RAS WT and all study population (referred as "both populations"
    below). Kaplan-Meier (KM) estimates for OS and KM survival curves will
    also be presented for each treatment arm and both populations. The KM
    estimates at time points such as 3 months, 6 months etc. together with
    corresponding 95% confidence intervals as well as the differences of
    these estimates will also be calculated between the rogaratinib arm and
    the chemotherapy arm for both populations.
    This study follows a Phase 2/3 design with interim analysis, meaning the
    patients recruited to the Phase 2 part of the study will automatically
    continue to the Phase 3 part without interruption if futility is not
    demonstrated at the 1st interim ORR analysis. The Phase 2 part will end
    at the time of the cut-off for the 1st interim ORR analysis. To help
    structure the protocol flow, we present this Phase 2/3 study as one
    study protocol with two interim analyses, while the first interim
    indicates the end of the Phase 2 part, and the second and final analyses
    are considered as the Phase 3 part including Phase 2 patients in the
    analyses.
    La variabile primaria di efficacia è la sopravvivenza globale (OS). I dati relativi all’OS saranno considerati maturi e l’analisi finale riguardante l’OS (analisi primaria di completamento) sarà eseguita dopo il decesso di un totale approssimativo di 232 pazienti con PIK3CA e RAS WT, in conformità ai calcoli di potenza specificati per il full analysis set (FAS). Per la variabile primaria di efficacia di sopravvivenza globale, sarà condotto prima un test log rank stratificato con controllo dell’errore di tipo I a un livello di 0,025 (a una coda) per la popolazione WT (step 1). Un alfa completo di 0,025 (a una coda) sarà applicato all’OS in tutte le popolazioni dello studio e ad alcuni endpoint secondari selezionati (step 2) se, e soltanto se, l’ipotesi nulla dell’OS per la popolazione WT sarà rigettata. Informazioni dettagliate sul controllo dell’errore di tipo I family-wise nell’ambito dello step 2 per l’OS nell’intera popolazione dello studio ed endpoint secondari selezionati saranno specificate nel Piano di analisi statistica (SAP). Inoltre, l’hazard ratio (rogaratinib/chemioterapia) per l’OS e il relativo intervallo di confidenza al 95% saranno calcolati utilizzando il modello di Cox, stratificato in base ai medesimi fattori utilizzati per la randomizzazione, sia per la popolazione con PIK3CA e RAS WT sia per l’intera popolazione dello studio (denominate “entrambe le popolazioni” nel prosieguo). Anche le stime di Kaplan-Meier (KM) per l’OS e le curve di sopravvivenza di KM saranno presentate per ciascun braccio di trattamento e per entrambe le popolazioni. Anche le stime di KM in corrispondenza di intervalli temporali quali 3 mesi, 6 mesi, ecc., insieme ai corrispondenti intervalli di confidenza al 95%, e le differenze di tali stime saranno calcolati tra il braccio rogaratinib e il braccio chemioterapia per entrambe le popolazioni.
    Questo studio segue un disegno di fase 2/3 con analisi ad interim. Ciò significa che se in occasione della 1a analisi ORR intermedia non ne sarà dimostrata la inutilità, i pazienti reclutati per la fase 2 dello studio proseguiranno automaticamente con la fase 3, senza alcuna interruzione. La fase 2 terminerà in corrispondenza del cut-off per la 1a analisi ORR ad interim. Per agevolare la strutturazione dello schema del protocollo, presentiamo questo studio di fase 2/3 come un solo protocollo dello studio con due analisi ad interim, in cui la prima analisi ad interim segna la fine della fase 2, mentre la seconda analisi ad interim e l’analisi finale costituiscono la fase 3 e includono i pazienti della fase 2.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Final OS analysis: at approx. 232 deaths in WT population (approx. 44.9
    months after the start of randomization).
    In addition, two interim analyses are planned:
    1st interim ORR analysis (Phase 2 part):
    At approx. the first 116 PIK3CA and RAS WT patients complete 4.5
    months of Treatment.
    2nd interim OS analysis (Phase 3 part):
    At approx. 116 deaths in PIK3CA and RAS WT patients (50% of 232 total
    death events in WT population, approx. 28.7 months after start of
    randomization).
    Analisi finale dell’OS: al raggiungimento di circa 232 decessi nella popolazione WT (circa 44,9 mesi dopo l’inizio della randomizzazione).
    Sono, inoltre, previste due analisi intermedie:
    • 1a analisi ORR ad interim (fase 2): all’incirca quando i primi 116 pazienti con PIK3CA e RAS WT avranno completato 4,5 mesi di trattamento
    2a analisi OS ad interim (fase 3): all’incirca dopo 116 decessi tra i pazienti con PIK3CA e RAS WT (50% dei 232 eventi di decesso totali nella popolazione WT, circa 28,7 mesi dopo l’inizio della randomizzazione)
    E.5.2Secondary end point(s)
    Vedere Allegato I Appendice 5 (26.01.2018)
    Vedere Allegato I Appendice 5 (26.01.2018)
    E.5.2.1Timepoint(s) of evaluation of this end point
    Secondary efficacy variables will be analyzed based on final database when approximately a total of 232 PIK3CA and RAS WT patients have died (approx. 44.9 months after the start of randomization).
    Le variabili di efficacia secondaria saranno analizzate nel database finale dopo il decesso di un totale approssimativo di 232 PIK3CA e RAS wt (appross. 44.9 mesi dopo l'inizio della randomizzazione)
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis Yes
    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 Yes
    E.6.10Pharmacogenetic Yes
    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) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    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 EEA107
    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
    Austria
    Belgium
    Brazil
    Canada
    China
    Czech Republic
    Denmark
    Finland
    France
    Germany
    Hong Kong
    Hungary
    Ireland
    Israel
    Italy
    Japan
    Korea, Republic of
    Netherlands
    Poland
    Portugal
    Russian Federation
    Singapore
    Slovakia
    Spain
    Sweden
    Switzerland
    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
    For each participating EU country, the end of the study according to the
    EU Clinical Trial Directive will be reached when the last visit of the last
    patient for all centers in the respective country has occurred.
    The end of the study as a whole will be reached when the last visit of
    the last patient has been achieved in all participating centers (EU and
    non-EU), or the primary completion event has been reached, whichever
    comes later.
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months2
    E.8.9.1In the Member State concerned days29
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months7
    E.8.9.2In all countries concerned by the trial days11
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1Number of subjects for this age range: 1
    F.1.1.1In Utero Information not present in EudraCT
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) Information not present in EudraCT
    F.1.1.3Newborns (0-27 days) Information not present in EudraCT
    F.1.1.4Infants and toddlers (28 days-23 months) Information not present in EudraCT
    F.1.1.5Children (2-11years) Information not present in EudraCT
    F.1.1.6Adolescents (12-17 years) Information not present in EudraCT
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 976
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 651
    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 Yes
    F.3.3.2Women of child-bearing potential using contraception No
    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 state81
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 925
    F.4.2.2In the whole clinical trial 1627
    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)
    none
    nessuno
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2018-04-26
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-02-27
    P. End of Trial
    P.End of Trial StatusCompleted
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA