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   43871   clinical trials with a EudraCT protocol, of which   7290   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:2011-001138-40
    Sponsor's Protocol Code Number:IOM-605
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2011-09-08
    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 ConcernedGermany - BfArM
    A.2EudraCT number2011-001138-40
    A.3Full title of the trial
    First Line Pazopanib in Poor Risk Patients with Metastatic Renal Cell Carcinoma
    Einarmige, multizentrische Studie zur Bewertung von Pazopanib als Erstlinientherapie in Hochrisikopatienten mit fortgeschrittenem oder metastasierendem Nierenzellkarzinom
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    First Line Pazopanib in Poor Risk Patients with Metastatic Renal Cell Carcinoma
    Einarmige, multizentrische Studie zur Bewertung von Pazopanib als Erstlinientherapie in Hochrisikopatienten mit fortgeschrittenem oder metastasierendem Nierenzellkarzinom
    A.3.2Name or abbreviated title of the trial where available
    FLIPPER
    A.4.1Sponsor's protocol code numberIOM-605
    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 SponsoriOMEDICO AG
    B.1.3.4CountryGermany
    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 supportNovartis AG
    B.4.2CountryGermany
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationiOMEDICO AG
    B.5.2Functional name of contact pointiOMEDICO AG
    B.5.3 Address:
    B.5.3.1Street AddressHanferstr. 28
    B.5.3.2Town/ cityFreiburg
    B.5.3.3Post code79108
    B.5.3.4CountryGermany
    B.5.4Telephone number0049761152420
    B.5.5Fax number00497611524280
    B.5.6E-mailinfo@iomedico.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 Yes
    D.2.1.1.1Trade name Votrient
    D.2.1.1.2Name of the Marketing Authorisation holderNovartis Europharm Limited
    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.3.1Product nameVotrient
    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 INNPAZOPANIB
    D.3.9.1CAS number 444731-52-6
    D.3.9.4EV Substance CodeSUB29175
    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 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
    Locally advanced or metastatic renal cell carcinoma
    lokal fortgeschrittener oder metastasierter Nierzellkrebs
    E.1.1.1Medical condition in easily understood language
    Locally advanced or metastatic renal cell carcinoma
    lokal fortgeschrittener oder metastasierter Nierzellkrebs
    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 10038407
    E.1.2Term Renal cell cancer
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Primary analysis will focus on the rate of poor risk patients as defined by the MSKCC criteria who are free of disease progression at 6 months after start of first line treatment with pazopanib.
    E.2.2Secondary objectives of the trial
    - Estimate the progression free survival of patients treated with pazopanib
    - To assess overall survival of poor risk patients treated with pazopanib.
    - To assess the overall response rate (ORR) according to RECIST-criteria 1.1 and the duration of response
    - To assess the safety profile of pazopanib in first line poor risk patients
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Explorative analysis - Biomarker:

    - Assessment of the pre- and post-treatment pattern of circulating markers in serum samples (e.g. cytokines, metalloproteases, apoptosis markers)
    - Assessment of the pre- and post-treatment changes in circulating markers of angiogenesis (e.g. VEGF, sVEGFR2) in plasma samples.
    - Assessment of the effect of the pre- and post-treatment pattern of circulating markers with regard to progression free survival of patients treated with pazopanib.
    - Assessment of the effect of pre- and post-treatment patterns of circulating markers of angiogenesis with regard to progression free survival of patients treated with pazopanib.
    - Determination of the baseline expression levels of pVHL and its associated pathway (e.g. pS6, pAKT, PTEN) in archival tumor samples when available.
    - To assess mutational status of genes involved in pathway deregulation e.g. VHL, PTEN, PI3KCA, in tumor samples, when available.
    - Assessment of the pazopanib trough levels
    - Assessment of the pre- and post-treatment changes in circulating genomic tumor markers (e.g. CpG island hypermethylation, cell-free circulation DNA, miRNA) in serum plasma samples.
    - Assessment of serum levels of pazopanib
    - Assessment of serum biomarkers, influenced by Pazopanib which might be used as predictive tool (e.g. chemokines like IL-8, apoptosis markers, VEGF)

    Explorative analysis - DCE-MRI:
    Functional MRI in selected sites
    Assessment ofs functional MRI-parameters (e. g. DCE-MRI, DWI and T1-quantification) at baseline and during pazopanib treatment as potential biomarkers (selected sites only)
    E.3Principal inclusion criteria
    1. Histologically confirmed metastatic or locally advanced (defined as non operable tumor), predominantly clear cell renal cell carcinoma.
    2. At least three of the following six predictors of short survival are required:
    o LDH > 1.5 x ULN
    o Hemoglobin < LLN
    o corrected serum calcium level > 10 mg/dl (2.5 mmol/l)
    o time from initial diagnosis of renal-cell carcinoma to occurrence of metastases of less than 1 year
    o Karnofsky Status of 60 or 70
    3. Karnofsky Status ≥ 60
    4. Age ≥ 18 years or legal age of consent if greater than 18 years
    5. Dated and signed written informed consent prior to performance of study-specific procedures or assessments
    E.4Principal exclusion criteria
    - Other malignancy. (Patients who have undergone prior radical or partial nephrectomy for RCC are allowed). Subjects who have had another malignancy and have been disease-free for five years, or subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible.
    - Prior systemic treatment for renal cell carcinoma. (NB: all treatments, neo-adjuvant, adjuvant or for locally advanced or metastatic RCC are not permitted.)
    - History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for 6 months prior to first dose of study drug. Screening with CNS imaging studies (computed tomography (CT) or magnetic resonance imaging (MRI) is required only if clinically indicated or if the subject has a history of CNS metastases.
    - Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:
    o Active peptic ulcer disease
    o Known intraluminal metastatic lesion/s with risk of bleeding
    o Inflammatory bowel disease (e.g. ulcerative colitis, Chrohn’s disease), or other gastrointestinal conditions with increased risk of perforation
    o History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment
    - History of any one or more of the following cardiovascular conditions within the past 6 months:
    o Myocardial infarction
    o Cardiac angioplasty or stenting
    o Unstable angina
    o Coronary artery bypass graft surgery
    o Symptomatic peripheral vascular disease
    o Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA)
    - Poorly controlled hypertension (defined as systolic blood pressure (SBP) of ≥140 mmHg or diastolic blood pressure (DBP) of ≥ 90mmHg). Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. BP must be re-assessed on two occasions at intervals of at least one hour if it is not <140/90 mmHg at baseline assesment. On each of these occasions, SBP / DBP values from each BP assessment must be <140/90 mmHg in order for a subject to be eligible for the study
    - Pregnant or breast-feeding women
    - Known hypersensitive reaction to any of the components of study treatments
    E.5 End points
    E.5.1Primary end point(s)
    Rate of poor risk patients as defined by the MSKCC criteria who are free of disease progression at 6 months after start of first line treatment with pazopanib.
    Ermittlung des Anteils der Hochrisikopatienten (definiert nach den MSKCC Kriterien), der 6 Monate nach Beginn der Erstlinienbehandlung mit Pazopanib progressionsfrei ist.
    E.5.1.1Timepoint(s) of evaluation of this end point
    6 months (26 weeks)
    6 Monate (26 Wochen)
    E.5.2Secondary end point(s)
    • To assess overall survival (OS) of poor risk patients treated with pazopanib.
    • To assess the safety profile of pazopanib in first line poor risk patients
    • To assess progression free survival (PFS) of patients treated with pazopanib
    • To assess overall response (ORR) rate and duration of response (DR) according to RECIST 1.1

    Explorative analysis (Biomarker):
    • Relation between biomarkers and clinical outcome (response, stable disease, progression of disease)
    Explorative analysis (DCE-MRI):
    • To assess the overall response rate (ORR) according to RECIST-criteria 1.1 and the duration of response to first line therapy with pazopanib
    • To assess early clinical effects of therapy with pazopanib starting from 7 days compared with 2 months after first dose.
    • To assess the functional effects of therapy with pazopanib, e.g. vascularization of the tumor including morphological changes according to RECIST 1.1
    • To assess the relationship of baseline parameters, early and late therapy effects with clinical outcome (overall and progression free survival)
    • Gesamtüberleben (OS) von Hochrisikopatienten, die mit Pazopanib behandelt wurden
    • Sicherheitsprofil von Hochrisikopatienten, die mit Pazopanib behandelt wurden
    • Schätzung des progressionsfreien Intervalls von mit Pazopanib behandelten Patienten
    • Gesamtansprechrate gemäß RECIST 1.1 und Dauer des Ansprechens

    Explorative Untersuchungen (Begleitprojekt Biomarker):
    • Die Beziehung zwischen Biomarkern und klinischem Nutzen (Ansprechen, stabile Erkrankung und Progression / kein klinischer Nutzen)

    Explorative Untersuchungen (Begleitprojekt DCE-MRI):
    • Gesamtansprechrate gemäß RECIST 1.1 sowie Dauer des Ansprechens und die prognostische Identifizierung von ansprechenden und nicht ansprechenden Patienten auf die Erstlinientherapie mit Pazopanib
    • Die Bewertung von frühen Effekten der Therapie mit Pazopanib ab 7 Tagen nach Beginn der Einnahme im Vergleich mit Therapieeffekten nach 2 Monaten
    • Die Korrelation von funktionellen Therapieeffekten wie z.B. Durchblutung des Tumors mit Veränderungen der Morphologie nach RECIST 1.1
    • Korrelation von baseline-Parametern, frühen und späten Therapieeffekten mit der klinischen Wirkung (Überleben, progressionsfreies Überleben)
    E.5.2.1Timepoint(s) of evaluation of this end point
    OS: date of death
    Safety profile: continuosly
    PFS: Day 1 of 9th and 17th week, after 6 months (26 weeks), after 32 weeks; after that period every 8 weeks until end of therapy
    ORR/DR: Day 1 of 9th and 17th week, after 6 months (26 weeks), after 32 weeks; after that period every 8 weeks until end of therapy
    Explorative Analyses: At Baseline, 2 weeks after start of therapy, on first day of cycles 2, 3, 5 and 7 and at end of therapy
    MRI substudy: Day 1, day 8 and week 8 of treatment
    OS: Tag des Todes
    Sicherheitsprofil: fortlaufend
    PFS: Tag 1 der 9. und 17. Therapiewoche, nach 6 Monaten (26 Wochen), nach 32 Wochen; danach alle 8 Wochen bis zum Therapieende
    ORR/DR: Tag 1 der 9. und 17. Therapiewoche, nach 6 Monaten (26 Wochen), nach 32 Wochen; danach alle 8 Wochen bis zum Therapieende
    Explorative Analysen: Zu Behandlungsbeginn, 2 Wochen nach Behandlungsbeginn, am ersten Tag des zweiten Zyklus sowie am ersten Tag von Zyklus 3, 5 und 7 und bei Therpieende
    MRI Substudie: An Tag 1, Tag 8 und in der 8. Therapiewoche
    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 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 No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    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 concerned10
    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
    End of the trial is defined as last visit of the last patient (LPLV).
    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 months6
    E.8.9.1In the Member State concerned days7
    E.8.9.2In all countries concerned by the trial years5
    E.8.9.2In all countries concerned by the trial months6
    E.8.9.2In all countries concerned by the trial days7
    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: 44
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 44
    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 state44
    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)
    normal treatment of condition
    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 Decision2011-11-16
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2011-11-17
    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-Thu May 02 00:31:05 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA