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    Summary
    EudraCT Number:2011-005983-12
    Sponsor's Protocol Code Number:INT01/12
    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:2012-03-07
    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 number2011-005983-12
    A.3Full title of the trial
    Phase II study of the fully human monoclonal antibody against transforming growth factor-beta (TGF-beta) receptor ALK1 (PF-03446962) in relapsed or refractory urothelial cancer (UC) failing first-line treatment.
    Studio di fase II con PF-03446962, anticorpo monoclonale anti-ALK1 (recettore del Transforming Growth Factor-TGF-beta), in pazienti affetti da neoplasie uroteliali in fase localmente avanzata/metastatica ricaduti o refrattari alla prima linea di trattamento chemioterapico.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Trial aimed at evaluating the activity of the anti-ALK1 monoclonal antibody PF-03446962 in relapsed or refractory urothelial cancer (UC) failing first-line treatment.
    Studio che ha lo scopo di valutare l’attivita' antitumorale e la tollerabilita' dell’anticorpo monoclonale anti-ALK1 PF-03446962 in pazienti affetti da neoplasie uroteliali metastatiche ricadute/refrattarie.
    A.3.2Name or abbreviated title of the trial where available
    PF-03446962 (anti-ALK-1 mAb) in relapsed/refractory Urothelial Cancer
    PF-03446962 nel carcinoma uroteliale refrattario
    A.4.1Sponsor's protocol code numberINT01/12
    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 SponsorISTITUTO NAZIONALE PER LA CURA TUMORI
    B.1.3.4CountryItaly
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportFondazione IRCCS Istituto Nazionale dei Tumori Milano
    B.4.2CountryItaly
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationFondazione IRCCS Istituto Nazionale dei Tumori Milano
    B.5.2Functional name of contact pointUrologia
    B.5.3 Address:
    B.5.3.1Street Addressvia G. Venezian 1
    B.5.3.2Town/ cityMilano
    B.5.3.3Post code20133
    B.5.3.4CountryItaly
    B.5.4Telephone number02 2390 2402
    B.5.5Fax number02 2390 2708
    B.5.6E-mailandrea.necchi@istitutotumori.mi.it
    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 nameNA
    D.3.2Product code PF-03446962
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNNA
    D.3.9.1CAS number NA
    D.3.9.2Current sponsor codePF-03446962
    D.3.9.3Other descriptive nameNA
    D.3.9.4EV Substance CodeNA
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product Yes
    D.3.11.13.1Other medicinal product typeanticorpo monoclonale
    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
    Relapsed or refractory urothelial cancer after failure of 1st line platinum-containing chemotherapy regimen for metastatic disease.
    Carcinoma a cellule transizionali della vescica o delle vie urinarie in fase localmente avanzata o metastatica. In particolare, i pazienti eleggibili al trattamento sono coloro che hanno già ricevuto 1 linea di trattamento chemioterapico platino-contenente per malattia metastatica o coloro che sono ricaduti entro e non oltre 6 mesi da un precedente trattamento perioperatorio (adiuvante/neoadiuvante).
    E.1.1.1Medical condition in easily understood language
    Advanced urothelial cancers relapsing/not responding to prior chemotherapy regimen.
    Neoplasie dell'urotelio (vescica ed alte vie urinarie) in fase localmente avanzata/metastatica ed in ricaduta dopo prima linea di chemioterapia.
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level HLT
    E.1.2Classification code 10038502
    E.1.2Term Renal pelvis and ureter neoplasms malignant
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level PT
    E.1.2Classification code 10044410
    E.1.2Term Transitional cell cancer of the renal pelvis and ureter recurrent
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level PT
    E.1.2Classification code 10044412
    E.1.2Term Transitional cell carcinoma
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level PT
    E.1.2Classification code 10066750
    E.1.2Term Bladder transitional cell carcinoma recurrent
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the activity of the drug in patients with relapsed/refractory transitional cell tumors receiving the following treatment program: IV doses of PF-03446962 monotherapy fortnightly until disease progression or onset of unacceptable toxicity.
    Valutare l’attività di PF-03446962 in pazienti affetti da carcinoma uroteliale avanzato ricaduti o refrattari.
    E.2.2Secondary objectives of the trial
    To evaluate the safety and tolerability of PF-03446962 monotherapy in a population of chemotherapy pretreated patients with UC.
    Valutare la sicurezza e la tollerabilità di PF-03446962 somministrato in monoterapia in una popolazione di pazienti pre-trattati.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    • Age > 18 years. • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. • Life expectancy of at least 12 weeks. • Histologically confirmed diagnosis of transitional cell tumors of the bladder or the urothelium. Presence of divergent histologies (ex. Squamous-cell histology) may be acceptable provided that there is prevalence of urothelial component. • Locally advanced/Metastatic disease. • Measurable disease criteria, defined as ≥ 1 unidimensionally measurable lesion ≥ 2 cm by conventional techniques or ≥ 1 cm by spiral CT scan. • Failure of no more than 1 cisplatin-based conventional chemotherapy regimen for metastatic disease (pure second-line setting). • Neoadjuvant/adjuvant therapy considered if relapse occurred within 6 months of the last cycle of chemotherapy.
    • Consenso informato scritto. • Età ≥ 18 anni. • Diagnosi istologicamente confermata di carcinoma a cellule transizionali della vescica o delle vie urinarie. • Malattia localmente avanzata/metastatica. • Ricaduta/progressione dopo 1 linea di trattamento chemioterapico platino (cis- o carboplatino) contenente per malattia metastatica. • Ricaduta/progressione entro 6 mesi da un precedente trattamento peri-operatorio platino-contenente. • Malattia misurabile, definita come la presenza di ≥ 1 lesione misurabile uni-dimensionalmente con metodiche convenzionali (TC) di ≥ 2 cm o di ≥ 1 cm se misurata con TC spirale.
    E.4Principal exclusion criteria
    • Treatment with any of the following anti-cancer therapies: o radiation therapy, surgery or tumor embolization within 14 days prior to the first dose of PF-03446962 OR o chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of PF-03446962. • cardiovascular conditions within the past 6 months. • History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis.
    • Ogni chemioterapia o immunoterapia sia durante il trattamento che entro i 14 giorni precedenti l’arruolamento nello studio (o 5 volte il tempo dell’emivita del farmaco). • Radioterapia, chirurgia o embolizzazione tumorale durante o entro 14 giorni dall’arruolamento nello studio (la radioterapia a scopo palliativo è ammessa). • Importanti patologie cardiovascolari nei 6 mesi che precedono l’inizio di PF-03446962. • Metastasi cerebrali o meningee sintomatiche.
    E.5 End points
    E.5.1Primary end point(s)
    2-month progression-free survival rate
    Progression-free survival (PFS) a 2 mesi.
    E.5.1.1Timepoint(s) of evaluation of this end point
    2-month
    2 mesi
    E.5.2Secondary end point(s)
    • Assessment of the safety and tolerability: incidence, nature and severity of treatment-related adverse events (AEs) will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) v4.03. • Assessment of response-rate by RECIST v1.1 criteria. RR (%) = CR + PR. • Response-rate according to densitometry (CT). • Overall Survival. • 2-month PFS in the per protocol population. • Correlation of PET response with CT response (RECIST and densitometry) and with PFS. • Quality of life changes according to ESAS score. • Correlative endpoints.
    • Valutazione della sicurezza e della tollerabilità del trattamento: o Numero di pazienti che hanno avuto eventi avversi. o Tipo, frequenza, severità e correlazione al trattamento degli eventi avversi, valutati secondo i Common Terminology Criteria for Adverse Events (CTCAE) v4.03. • Valutazione del response-rate (RR) definito scondo i criteri RECIST 1.1. RR (%) = Risposte complete (RC) + risposte parziali (PR). o RC = Scomparsa di tutte le lesioni target; ogni linfonodo patologico deve avere una riduzione fino ad un diametro minore < 10 mm. o RP = Riduzione di almeno il 30% della somma dei diametri delle lesioni target, prendendo come riferimento la somma dei diametri basali. • RR valutato in base alla densitometria TC (per dettagli vedere il paragrafo 11 del full protocol). • PFS nella “per protocol population”. • Sopravvivenza globale (OS). • Correlazione della risposta metabolica (PET) con la risposta TC (RECIST e densitometria) e con la PFS. • Variazione dello score di qualità della vita durante il trattamento valutato con l’ESAS (Edmonton Symptom Assessment Scale). • Altri obiettivi di ricerca traslazionale (Biomarkers).
    E.5.2.1Timepoint(s) of evaluation of this end point
    variable
    variabile
    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 No
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    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 No
    E.8.1.1Randomised Information not present in EudraCT
    E.8.1.2Open Information not present in EudraCT
    E.8.1.3Single blind Information not present in EudraCT
    E.8.1.4Double blind Information not present in EudraCT
    E.8.1.5Parallel group Information not present in EudraCT
    E.8.1.6Cross over Information not present in EudraCT
    E.8.1.7Other Information not present in EudraCT
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Information not present in EudraCT
    E.8.2.2Placebo Information not present in EudraCT
    E.8.2.3Other Information not present in EudraCT
    E.8.2.4Number of treatment arms in the trial1
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.4.1Number of sites anticipated in Member State concerned1
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee No
    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
    If the study is stopped before entering stage 2, survival data will be collected until the cut off date, defined as 4 months after the last patient enters the trial. If the study continues on the stage 2 but <30% of patients are surviving, then the survival data will be collected until the cut off date. However, if the study continues in stage 2 and ≥30% of patients are surviving, the collection of survival data will be extended to additional 4 months from the cut off date.
    4 mesi dall'arruolamento dell'ultimo paziente (+ eventuali altri 4 mesi nel caso in cui lo studio continui nello stadio 2 e >= 30% dei pazienti sono vivi).
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years0
    E.8.9.1In the Member State concerned months19
    E.8.9.1In the Member State concerned days0
    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: 0
    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: 35
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 10
    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 state45
    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)
    All patients, regardless of whether or not they discontinued prior to or subsequent to disease progression, will be followed every 2 months for updates of initiation of next therapy and overall survival until tha date of data cut-off for the final analysis.
    Tutti i pazienti verranno seguiti ogni 2 mesi per aggiornamento sulla sopravvivenza o inizio di ulteriore terapia, fino alla data di conclusione dello studio.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2012-03-21
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2012-01-24
    P. End of Trial
    P.End of Trial StatusOngoing
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    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
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