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    The EU Clinical Trials Register currently displays   44338   clinical trials with a EudraCT protocol, of which   7368   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).

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    Summary
    EudraCT Number:2017-002470-40
    Sponsor's Protocol Code Number:PROSORA
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2017-08-16
    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 ConcernedNetherlands - Competent Authority
    A.2EudraCT number2017-002470-40
    A.3Full title of the trial
    Observational study of the effects of probenecid on the pharmacokinetics and pharmacodynamics of sorafenib (PROSORA-study)
    Een observationele studie naar de effecten van probenecid op de farmacokinetiek en farmacodynamiek van sorafenib (PROSORA-studie)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Observational study of the effects of probenecid on the metabolism and working mechanism of sorafenib (PROSORA-study)
    Observationele studie naar de effecten van probenecid op het metabolisme en werkingsmechanisme van sorafenib (PROSORA-studie)
    A.3.2Name or abbreviated title of the trial where available
    PROSORA-studie
    A.4.1Sponsor's protocol code numberPROSORA
    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 SponsorErasmus MC Cancer Institute
    B.1.3.4CountryNetherlands
    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 supportErasmus MC
    B.4.2CountryNetherlands
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationErasmus MC
    B.5.2Functional name of contact pointRon Mathijssen
    B.5.3 Address:
    B.5.3.1Street Address's Gravendijkwal 230
    B.5.3.2Town/ cityRotterdam
    B.5.3.3Post code3015CE
    B.5.3.4CountryNetherlands
    B.5.6E-maila.mathijssen@erasmusmc.nl
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Sorafenib
    D.2.1.1.2Name of the Marketing Authorisation holderBayer Pharma AG
    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.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Probenecid
    D.2.1.1.2Name of the Marketing Authorisation holderMylan
    D.2.1.2Country which granted the Marketing AuthorisationUnited States
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameProbenecid
    D.3.2Product code M04AB01
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    patients with unresectable hepatocellular cancer, advanced clear-cell renal cell carcinoma, locally recurrent or metastatic, progressive, differentiated thyroid carcinoma refractory to radioactive iodine treatment.
    Patienten met niet resectabel HCC, gevorderd RCC, lokaal gerecidiveerd, gemetastaseerd, progressief of gedifferentieerd schildkliercarcinoom refractair na behandeling met radioactief jodium.
    E.1.1.1Medical condition in easily understood language
    Liver cancer, Renal cancer or a certain type of thyroid cancer
    leverkanker, nierkanker of een bepaald type schildklierkanker
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To demonstrate the bioequivalence of sorafenib with probenecid relative to sorafenib without probenecid based on the AUC in patients with unresectable hepatocellular cancer, advanced clear-cell renal cell carcinoma, locally recurrent or metastatic, progressive, differentiated thyroid carcinoma refractory to radioactive iodine treatment.
    Bioequivalentie aantonen van sorafenib met probenecid tov sorafenib zonder probenecid gebaseerd op de AUC.
    E.2.2Secondary objectives of the trial
    1. Other pharmacokinetic outcomes (i.e. clearance, maximum concentration (Cmax), Minimal concentration (Cmin), steady-state volume of distribution (Vss) and half-life (t½)).
    2. To evaluate the incidence and severity of side-effects of treatment with sorafenib in absence and presence of probenecid (in particular HFSR) .
    3. To evaluate the intracellular concentration of sorafenib in skin in patients treated with sorafenib in absence and presence of probenecid.
    1. Andere farmacokinetische uitkomsten (klaring, maximale concentratie (Cmax), minimale concentratie (Cmin), steady-state volume van verdeling (Vss) en halfwaardetijd (t1/2)
    2. incidentie en ernst van bijwerkingen van de behandeling met sorafenib in aan- en afwezigheid van probenecid onderzoeken (mn hand-voetsyndroom)
    3. Intracellulaire concentratie van sorafenib in de huid van patienten bepalen, die met sorafenib in aan- of afwezigheid van probenecid worden behandeld.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Age ≥ 18 years
    2. Histological or cytological confirmed diagnosis of mRCC, HCC or differentiated thyroid carcinoma
    3. Start of sorafenib therapy, at least 7 days prior to start of the study NB. Patients are allowed to have had previous sorafenib therapy or have started with sorafenib.
    4. WHO Performance Status ≤ 2 (appendix D)
    5. Able and willing to sign the Informed Consent Form prior to screening evaluations
    6. Adequate organ function as defined by:
    a. Total bilirubin ≤ 1.5 x ULN (except in case of documented Gilbert’s disease)
    b. ASAT ≤ 3.0 x ULN (or ≤ 5 x ULN if liver metastases are present)
    c. ALAT ≤ 3.0 x ULN (or ≤ 5 x ULN if liver metastases are present)
    d. Serum creatinin ≤ 1.5 x ULN
    7. Adequate baseline patient characteristics (complete blood count, and serum biochemistry which involves sodium, potassium, creatinin, calculation of creatinin clearance (MDRD), amylase, lipase, calcium, phosphate, AST, ALT, gamma glutamyltranspeptidase (-GT), lactate dehydrogenase (LDH), ALP, total bilirubin, albumin).
    1. Leeftijd >18 jaar
    2. Histologisch of cytologisch bevestigde diagnose van gemetastaseerd RCC, gedifferentieerd schildkliercarcinoom of HCC
    3. start van sorafenib therapie, tenminste 7 dagen voorafgaand aan de start van de studie NB. patienten mogen vooraf sorafenib hebben gehad of zijn gestart met sorafenib.
    4. WHO performance status <2
    5. Patient moet het toestemmingsformulier willen tekenen
    6. adequate orgaanfunctie gedefinieerd door
    a. totaal billirubine ≤ 1.5 x ULN (behalve als iemand bekend is met de ziekte van Gilbert)
    b. ASAT ≤ 3.0 x ULN (of ≤ 5 x ULN of als er sprake is van levermetastasen)
    c. ALAT ≤ 3.0 x ULN (of ≤ 5 x ULN of als er sprake is van levermetastasen)
    d. serum kreatinine ≤ 1.5 x ULN
    7. adequate baseline patientkarakteristieken (volledige bloedbeeld en plasma biochemie waaronder Natrium, Kalium, kreatinine, GFR, Amylase, lipase, calcium, fosfaat, ASAT, ALAT, GGT, LDH, AF, Totaal billirubine, albumine
    E.4Principal exclusion criteria
    1. Use of drugs which may show an increased systemic exposure when taken concomitantly with probenecid. (see appendix C)
    2. Patients with known blood dyscrasias, uric acid kidney stones or until an acute gouty attack has subsided.
    3. Use of (over the counter) medication or (herbal) supplements which can interact with either sorafenib or probenecid, e.g. by induction or inhibition of CYP3A4, UGT1A9 (see appendix B and C)
    4. Unable or unwilling to abstain from grapefruit, grapefruit juice, herbal dietary supplements, and herbal tea during the study
    5. Previous use of probenecid during the last 2 weeks prior to sorafenib treatment
    6. Contraindications for use of probenecid such as acute gouty attack or porphyria.
    7. Unwilling to undergo a skin biopsy
    1. gebruik van medicatie die kan zorgen voor een toegenomen systemische blootstelling wanneer ze samen ingenomen worden met probenecid
    2. patienten met hematologische problematiek, nierstenen obv urinezuur of patienten met een jichtaanval
    3. gebruik van (OTC) medicatie of (kruiden) supplementen die een interactie hebben met sorafenib of probenecid obv inductie of inhibitie van CYP3A4 of UGT1A9
    4. niet in staat of niet willend te stoppen met grapefruit, grapefruit sap, kruiden preparaten of kruidenthee tijdens de studie
    5. probenecid gebruikt in de 2 weken voorafgaand aan de studie
    6. contraindicaties voor het gebruik van probenecid zoals een acute jichtaanval of porfyrie
    7. Niet willen ondergaan van een huidbiopt
    E.5 End points
    E.5.1Primary end point(s)
    To demonstrate the bioequivalence of sorafenib with probenecid relative to sorafenib without probenecid based on the AUC in patients with unresectable hepatocellular cancer, advanced clear-cell renal cell carcinoma, locally recurrent or metastatic, progressive, differentiated thyroid carcinoma refractory to radioactive iodine treatment.
    Bioequivalentie aantonen van sorafenib met probenecid tov sorafenib zonder probenecid gebaseerd op de AUC.
    E.5.1.1Timepoint(s) of evaluation of this end point
    End of study
    Einde van de studie
    E.5.2Secondary end point(s)
    1. Other pharmacokinetic outcomes (i.e. clearance, maximum concentration (Cmax), Minimal concentration (Cmin), steady-state volume of distribution (Vss) and half-life (t½)).
    2. To evaluate the incidence and severity of side-effects of treatment with sorafenib in absence and presence of probenecid (in particular HFSR) .
    3. To evaluate the intracellular concentration of sorafenib in skin in patients treated with sorafenib in absence and presence of probenecid.
    1. Andere farmacokinetische uitkomsten (klaring, maximale concentratie (Cmax), minimale concentratie (Cmin), steady-state volume van verdeling (Vss) en halfwaardetijd (t1/2)
    2. incidentie en ernst van bijwerkingen van de behandeling met sorafenib in aan- en afwezigheid van probenecid onderzoeken (mn hand-voetsyndroom)
    3. Intracellulaire concentratie van sorafenib in de huid van patienten bepalen, die met sorafenib in aan- of afwezigheid van probenecid worden behandeld.
    E.5.2.1Timepoint(s) of evaluation of this end point
    End of study
    Einde van de studie
    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 No
    E.6.4Safety Yes
    E.6.5Efficacy No
    E.6.6Pharmacokinetic Yes
    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) No
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) Yes
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over Yes
    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
    The comparator is probenecid
    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.8.5The 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
    LVLS
    Laatste visite van de laatste patient
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months0
    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.1.1.1In 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: 12
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 4
    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 No
    F.3.3.1Women of childbearing potential not using contraception No
    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 state16
    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)
    Patients can continue the use of sorafenib post trial according to regular clinical practice
    Patienten kunnen doorgaan met de behandeling met sorafenib na de studie volgens de regulier geldende behandeling
    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 Decision2017-08-16
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-11-16
    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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