Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   37749   clinical trials with a EudraCT protocol, of which   6186   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).
     
    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:2013-003868-31
    Sponsor's Protocol Code Number:GANNET53
    National Competent Authority:Austria - BASG
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2013-12-20
    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 ConcernedAustria - BASG
    A.2EudraCT number2013-003868-31
    A.3Full title of the trial
    A two-part, multicentre, international phase I and II trial assessing the safety and efficacy of the Hsp90 inhibitor ganetespib in combination with paclitaxel weekly in women with high-grade serous, high-grade endometrioid, or undifferentiated, platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal cancer
    Eine zweiteilige, multizentrische, internationale Phase-I- und Phase-II-Studie zur Überprüfung der Sicherheit und Wirksamkeit des Hsp90-Inhibitors Ganetespib in Kombination mit Paclitaxel weekly bei Frauen mit hochgradig serösem, hochgradig endometroidem oder undifferenzierten, platinresistentem epithelialem Ovarial-, Tuben- oder primärem Peritonealkarzinom
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A two-part, phase I and II international trial conducted at a number of trial sites assessing the safety and efficacy of ganetespib, an inhibitor of the protein Hsp90, in combination with a weekly administration of the chemotherapeutic agent paclitaxel in women with platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal cancer
    Eine internationale Phase-I- und Phase-II-Studie in zwei Teilen und mehreren Zentren, um die Sicherheit und Wirksamkeit von Ganetespib, einem Hemmer des Eiweißmoleküls Hsp90, in Kombination mit der wöchentlichen Gabe des Chemotherapeutikums Paclitaxel bei Frauen mit platinresistentem epithelialem Eierstock-, Eileiter- oder primärem Bauchfellkrebs
    A.3.2Name or abbreviated title of the trial where available
    GANNET53: Ganetespib in metastatic, p53 mutant, platinum-resistant ovarian cancer
    GANNET53: Ganetespib bei metastasiertem, p53-mutiertem, platinresistentem Ovarialkarzinom
    A.4.1Sponsor's protocol code numberGANNET53
    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 SponsorMedizinische Universität Innsbruck, AGO Studienzentrale
    B.1.3.4CountryAustria
    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 supportEuropean 7th Framework
    B.4.2CountryEuropean Union
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAGO Studienzentrale
    B.5.2Functional name of contact pointProject Manager
    B.5.3 Address:
    B.5.3.1Street AddressAnichstraße 35
    B.5.3.2Town/ cityInnsbruck
    B.5.3.3Post code6020
    B.5.3.4CountryAustria
    B.5.4Telephone number004351250424132
    B.5.5Fax number004351250422458
    B.5.6E-mailago.studienzentrale@i-med.ac.at
    D. IMP Identification
    D.IMP: 1
    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
    D.2.1.2Country which granted the Marketing AuthorisationAustria
    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 and solvent for 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 INNPACLITAXEL
    D.3.9.1CAS number 33069-62-4
    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 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 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 nameGanetespib
    D.3.2Product code STA-9090
    D.3.4Pharmaceutical form Concentrate and solvent for 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 INNGanetespib
    D.3.9.3Other descriptive nameGANETESPIB
    D.3.9.4EV Substance CodeSUB88334
    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 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
    platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal cancer with mutant p53
    platinresistentes epitheliales Ovarial-, Tuben- oder primäres Peritonealkarzinom mit mutiertem p53
    E.1.1.1Medical condition in easily understood language
    platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal cancer with mutant protein p53
    platinresistenter epithelialer Eierstock-, Eileiter- oder primäres Bauchfellkrebs mit mutiertem Eiweißmolekül p53
    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
    Part I: to determine the safety of ganetespib + paclitaxel weekly

    Part II: to determine efficacy of ganetespib + paclitaxel weekly vs. paclitaxel weekly alone
    Teil I: Bestimmung der Sicherheit von Ganetespib+Paclitaxel weekly

    Teil II: Bestimmung der Wirksamkeit von Ganetespib + Paclitaxel weekly vs. Paclitaxel weekly allein
    E.2.2Secondary objectives of the trial
    Part I: to determine the ganetespib combination dose to be used in part II

    Part II: Patient related outcome, Pharmacokinetik
    Teil I: Bestimmung der Kombinationsdosis für Ganetespib in Teil II

    Teil II: Bestimmung der Lebensqualität, Pharmakokinetik
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    • Ability to understand and willingness to sign and date a written informed consent document
    • Female patients ≥18 years of age
    • High-grade serous, high-grade endometrioid, or undifferentiated epithelial ovarian, fallopian tube or primary peritoneal cancer.
    o Patients in part II: High-grade serous, high-grade endometrioid, or undifferentiated epithelial ovarian, fallopian tube or primary peritoneal cancer confirmed by central histophathology through archival FFPE or fresh-frozen tumour samples.
    • Platinum-resistant disease:
    o primary platinum-resistant disease: progression > 1 month and ≤ 6 months after completion of primary platinum-based therapy
    o secondary platinum-resistant disease (including secondary platinum-refractory disease): progression ≤ 6 months after (or during) reiterative platinum-based therapy
    • Patients must have disease that is measurable according to RECIST 1.1 or assessable according to the GCIG CA-125 criteria.
    • ECOG performance status of 0-1
    • Life expectancy of at least 3 months as assessed by the investigator
    • Adequate function of the bone marrow:
    o Platelets ≥100 x 10^9/L
    o Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
    • Haemoglobin ≥ 8.5 g/dl. Patients may receive blood transfusion(s) to maintain haemoglobin values > 8.5 g/dl.
    • Adequate organ functions:
    o Creatinine < 2 mg/dl (< 177 µmol/L)
    o Total bilirubin ≤ 1.5 x upper limit of normal
    o SGOT/SGPT (AST/ALT) ≤ 3 x upper limit of normal
    o Urinanalysis or urine dipstick for proteinuria less than 2+. Patients with ≥ 2+ on dipstick should undergo 24-hour urine collection and must demonstrate < 1 g of protein/24 hours. Alternatively, proteinuria testing can be performed according to local standards.
    • Adequate coagulation parameters: aPTT ≤ 1.5 x ULN (patients on heparin treatment must have an aPTT between 1.5 – 2.5 x ULN), or INR ≤ 1.5. (In patients receiving anticoagulants (such as warfarin) INR must be between 2.0 and 3.0 in two consecutive measurements 1-4 days apart).
    • Negative urine/serum pregnancy test in women of childbearing potential (WOCBP, see section 5). WOCBP who are sexually active agree to use highly effective means of contraception during the study and for at least 6 months post-study treatment. Allowed are accepted and effective non-hormonal methods of contraception and sexual abstinence or vasectomised partners (>3 months previously). Vasectomy has to be confirmed by two negative semen analyses.

    Only in part II of the trial:
    • Availability of archival ovarian cancer tissue for central histopathological review and p53 mutational analysis
    • Unterschriebene und datierte Einwilligungserklärung
    • Patientinnen ≥ 18 Jahre
    • Hochgradig seröses, hochgradig endometrioides oder undifferenziertes epitheliales Ovarial-, Tuben- oder primäres Peritonealkarzinom.
    o Patientinnen in Teil II: Hochgradig seröses, hochgradig endometrioides oder undifferenziertes epitheliales Ovarial-, Tuben- oder primäres Peritonealkarzinom, bestätigt durch die zentrale Histopathologie mittels archiviertem Paraffinblock oder frisch eingefrorenen Tumorproben.
    • Platinresistente Krankheit:
    o primär platinresistente Krankheit: Progression > 1 Monate und ≤ 6 Monaten nach Beedingung der primären platinbasierten Therapie
    o sekundär platinresistente Krankheit (einschl. sekundär platinrefraktäre Krankheit): Progression ≤ 6 Monate nach (oder während) wiederholter platinbasierter Therapie
    • messbare Krankheit nach RECIST 1.1 oder laut GCIG CA-125-Kriterien
    • ECOG Performance Status 0-1
    • Lebenserwartung mind. 3 Monate laut Beurteilung des Prüfarztes
    • Angemessene Funktion des Knochenmarks:
    o Thrombozyten ≥ 100 x 10^9/L
    o Absolute Neutrophilenzahl ≥ 1.5 x 10^9/L
    • Hämoglobin ≥ 8.5 g/dl. Patientinnen dürfen Bluttransfusionen erhalten, um Hämoglobinwerte > 8.5 g/dl aufrecht zu erhalten.
    • Angemessene Organfunktionen:
    o Creatinin < 2 mg/dl (< 177 µmol/L)
    o Bilirubin gesamt ≤ 1.5 x oberer Normwert
    o SGOT/SGPT (AST/ALT) ≤ 3 x oberer Normwert
    o Urinanalyse oder Harnstreifentest für Proteinurie unter 2+. Patientinnen mit ≥ 2+ am Harnstreifentest sollten eine 24-Stunden-Harnsammlung durchführen und < 1 g Protein/24 Stunden anzeigen. Alternativ kann der Test für Proteinurie nach lokalen Standards durchgeführt werden.
    • Angemessene Koagulationsparameter: aPTT ≤ 1.5 x ULN (Patientinnen unter Heparin Behandlung müssen einen aPTT Wert von 1.5 - 2.5 x ULN aufweisen), oder INR ≤ 1.5. (bei Patientinnen die Antikoagulantien (wie Warfarin) einnehmen, muss der INR bei zwei aufeinander folgenden Messungen, welche 1 - 4 Tage auseinander liegen, zwischen 2.0 und 3.0 sein
    • Negativer Schwangerschaftstest im Urin/Serum bei gebärfährigen Frauen. Gebärfähige Frauen, die sexuell aktiv sind, stimmen zu, während der Studie und mindestens 6 Monate lang nach der Studientherapie hochwirksame Verhütungsmethoden zu verwenden. Erlaubt sind akzeptierte und wirksame nicht-hormonelle Verhütungsmittel und sexuelle Abstinenz oder vasektomierte Partner (>3 Monate vorher). Die Vasektomie muss durch zwei negative Samenanalysen bestätigt werden.

    Nur bei Teil II der Studie:
    • Verfügbarkeit von archiviertem Ovarialtumorgewebe zur zentralen histopathologischen Überprüfungund p53-Mutationsanalyse
    E.4Principal exclusion criteria
    CANCER-RELATED:
    • Ovarian tumours with low malignant potential (ie. borderline tumours)
    - Carcinosarcoma of the Ovary
    • Primary platinum-refractory disease (progression during primary platinum-based chemotherapy)

    PRIOR, CURRENT OR PLANNED TREATMENT:
    • Previous treatment with > 2 chemotherapy regimens in the platinum-resistant setting (excluding targeted and endocrine therapies)
    - Previous weekly paclitaxel in relapse treatment
    • More than 4 previous lines of chemotherapy
    • Any prior radiotherapy to the pelvis or abdomen
    • Surgery (including open biopsy and traumatic injury) within 4 weeks prior to first dose of ganetespib, or anticipation of the need for major surgery during study treatment
    • Minor surgical procedures, within 24 hours prior to the first study treatment
    • Current or recent (within 10 days prior to the first study drug dose) chronic daily treatment with aspirin (>325 mg/day).
    • Chronic daily treatment with corticosteroids (dose >10 mg/day methylprednisolone equivalent), excluding inhaled steroids.

    PRIOR OR CONCOMITANT CONDITIONS OR PROCEDURES:
    • Patients with a history of prior malignancies, except,
    o disease-free time-frame of ≥ 3 years prior to randomisation
    • Patients with prior in-situ carcinomas, except:
    o complete removal of the tumour is given
    • Known history of severe (grade 3 or 4) allergic or hypersensitivity reactions to excipients (e.g., polyethylene glycol [PEG] 300 and Polysorbate 80)
    • History of intolerance or hypersensitivity to paclitaxel and/or adverse events related to paclitaxel that resulted in paclitaxel being permanently discontinued
    • Peripheral neuropathy of grade > 2 per NCI CTCAE, version 4.03, within 4 weeks prior to randomisation
    • Clinically significant gastro-intestinal (GI) tract abnormalities that may increase the risk for GI bleeding and/or perforation including but not limited to: active peptic ulcer disease, known intraluminal metastatic lesion/s with risk of bleeding, inflammatory bowel disease (e.g. ulcerative colitis, Crohn’s disease), history of bowel obstruction within 1 year prior to first study treatment (excluding postoperative, i.e. within 4 weeks post surgery), other GI condition with increased risk of perforation such as a recurrence deeply infiltrating into the muscularis or mucosa of the rectosigmoid or the mucosa of the bladder, or history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess
    • Non-healing wound or non-healing bone fracture
    • Patients with symptomatic brain metastases
    • Left ventricular ejection fraction defined by MUGA/ECHO below the institutional lower limit of normal
    • Cerebrovascular accident (CVA) / stroke or transient ischemic attack (TIA) or sub-arachnoid haemorrhage within ≤6 months prior to first study treatment.
    • Significant cardiac disease: New York Heart Association (NYHA) Class 3 or 4; myocardial infarction within the past 6 months; unstable angina; coronary angioplasty or coronary artery bypass graft (CABG) within the past 6 months; or uncontrolled atrial or ventricular cardiac arrhythmias
    • History of prolonged QT syndrome, or family member with prolonged QT syndrome
    • QTc interval > 470 msec when 3 consecutive EKG values are averaged
    • Ventricular tachycardia or a supraventricular tachycardia that requires treatment with a Class Ia antiarrhythmic drug (eg., quinidine, procainamide, disopyramide) or Class III antiarrhythmic drug (e.g., sotalol, amiodarone, dofetilide). Use of other antiarrhythmic drugs is permitted.
    • Second- or third-degree atrioventricular (AV) block, except:
    o treated with a permanent pacemaker
    • Complete left bundle branch block (LBBB)
    • History of evidence of haemorrhagic disorders, patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorders, coagulopathy or tumour involving major vessels
    • Any other condition that, in the opinion of the investigator, may compromise the safety, compliance of the patient, or would preclude the patient from successful completion of the study.
    • Participation in another clinical study with experimental therapy within 28 days before start of treatment
    • Women who are pregnant or are lactating
    IM ZUSAMMENHANG MIT KREBS:
    • Ovarialtumor mit niedrig-malignem Potential (z.B. Borderlinetumoren)
    - Carcinosarkom der Eierstöcke
    • Primär platinrefraktäre Krankheit (Progression während der primären platinbasierten Chemotherapie)

    VORHERIGE, MOMENTANE ODER GEPLANTE BEHANDLUNG:
    • Vorherige Behandlung mit > 2 Chemotherapie-Regimen im platinresistenten Setting (ausschließl. zielgerichtete und endokrine Therapien)
    - Vorheriges weekly Paclitaxel im Rezidiv
    • Mehr als 4 vorherige Chemotherapien
    • Strahlentherapie des Pelvis oder Abdomens
    • Operation (einschließlich offener Biopsie und traumatischer Verletzung) innerhalb 4 Wochen vor der ersten Ganetespibdosis, oder Annahme, dass eine größere Operation während der Studienbehandlung notwendig werden könnte.
    • Kleinere Operationen, innerhalb 24 Stunden vor der ersten Gabe der Studienmedikation.
    • Laufende oder kürzlich abgeschlossene (innerhalb 10 Tagen vor der ersten Dosis der Studienmedikation) dauerhafte tägliche Einnahme von Aspirin (>325 mg/Tag)
    • Dauerhafte tägliche Einnahme von Kortikosteroiden (Dosis >10 mg/Tag Methylprednisolon Äquivalent), ausschließlich zu inhalierender Steroide.

    FRÜHERE ODER BEGLEITENDE KRANKHEITEN ODER EINGRIFFE :
    • Patientinnen mit einer Vorgeschichte von früheren Malignitäten, außer
    o krankheitsfreie Zeit von ≥ 3 Jahren vor Randomisierung
    • Patientinnen mit führeren In-Situ-Karzinomen, außer:
    o vollständige Entfernung des Tumors ist gegeben
    • Bekannte Vorgeschichte von schweren (Grad 3 oder 4) allergischen oder hypersensiblen Reaktionen auf Trägerstoffe (z.B. Polyethylen glycol [PEG] 300 und Polysorbat 80)
    • Vorgeschichte von Unverträglichkeit oder Hypersensibilität auf Paclitaxel und/oder unerwünschte Ereignisse in Verbindung mit Paclitaxel, die dazu führten, dass die Gabe von Paclitaxel dauerhaft eingestellt wurde
    • Periphäre Neuropathie Grad > 2 laut NCI CTCAE, Version 4.03, innerhalb von 4 Wochen vor Randomisierung
    • Klinisch signifikante Abnormitäten des Magen-Darm-Traktes, die das Risiko für Magen-Darm-Blutungen und/oder Perforationen erhöhen können, unter anderem: aktive Ulkuskrankheit, bekannte intraluminale metastatische Läsion(en) mit Blutungsrisiko, entzündliche Darmerkrankung (z. B. Colitis ulcerosa, Morbus Crohn), Vorgeschichte einer Darmobstruktion innerhalb eines Jahres vor Beginn der Studienbehandlung (außer postoperativ, d. h. innerhalb von 4 Wochen nach Operation), andere Magen-Darm-Beschwerden mit erhöhtem Perforationsrisiko wie ein Rezidiv, das tief in die Muscularis oder Mucosa des Rektosigmoids oder die Mucosa der Blase infiltriert, oder eine Vorgeschichte von abdominalen Fisteln, gastrointestinalen Perforationen oder intra-abdominalem Abszess
    • Nichtheilende Wunde oder nichtheilende Knochenfraktur
    • Patientinnen mit symptomatischen Hirnmetastasen
    • Linksventrikuläre Auswurffraktion laut MUGA/Echo unterhalb des lokalen unteren Normwertes
    • Schlaganfall oder transiente ischemische Attacke (TIA) oder sub-arachnoidale Blutung innerhalb ≤6 Monaten vor der ersten Studienbehandlung.
    • Beträchtliche Herzerkrankung: New York Heart Association (NYHA) Klasse 3 oder 4; Myokardinfarkt innerhalb der letzten 6 Monate; unstabile Angina; koronäre Angioplastie oder Koronarartierenbypass innerhalb der letzten 6 Monate; oder unkontrollierte atriale oder ventrikuläre Herzarrythmien
    • Vorgeschichte von verlängertem QT-Syndrom oder Familienmitglied mit verlängertem QT-Syndrom
    • QTc-Intervall > 470 msek im Durchschnitt von 3 aufeinander folgenden EKG-Werten
    • Ventrikuläre Tachykardie oder supraventrikuläre Tachykardie, die Behandlung mit einem antiarrythmischem Medikament der Klasse 1a (z. B. Quinidin, Procainamid, Disopyramid) der Klasse III (z. B. Sotalol, Amiodaron, Dofetilid) erfordert. Die Verwendung von anderen antiarrhythmischen Medikamenten ist erlaubt.
    • Atrioventrikulärer (AV-)Block zweiten oder dritten Grades, außer:
    o mit permanentem Herzschrittmacher behandelt
    • Kompletter Linksschenkelblock
    • Vorgeschichte von nachgewiesenen Blutungsstörungen, Patienten mit aktiver Blutung oder pathologischen Beschwerden mit hohem Blutungsrisiko wie bekannte Blutgerinnungsstörungen, Koagulopathie oder Tumor mit Beteiligung der Hauptblutgefäßen
    • Jegliche andere Beschwerden, die nach Meinung des Prüfarztes die Sicherheit und Compliance der Patientin beeinträchtigen oder die Patientin an der erfolgreichen Beendigung der Studie behindern könnten.
    • Teilnahme an einer anderen klinischen Studie mit experimenteller Therapie innerhalb von 28 Tagen vor Beginn der Behandlung
    • Schwangere oder stillende Frauen
    E.5 End points
    E.5.1Primary end point(s)
    Part I
    • Safety: Adverse events (AEs) (measure according to NCI CTCAE, version 4.03), laboratory parameters, Eastern Cooperative Oncology Group (ECOG) performance status (PS), vital signs

    Part II
    • Progression-free survival (PFS) and PFS rates at 6 months
    Teil I
    • Sicherheit: Unerwünschte Ereignisse (AEs) (gemessen nach NCI CTCAE, Version 4.03), Laborwerte, Eastern Cooperative Oncology Group (ECOG) Performance Status (PS), Vitalparameter

    Teil II
    • Progressionsfreies Überleben (PFS) und PFS-Rate nach 6 Monaten
    E.5.1.1Timepoint(s) of evaluation of this end point
    Part I
    • Safety: days 1, 8, 15 of each cycle

    Part II
    • Progression-free survival (PFS) at 6 months and after end of trial
    Teil I
    • Sicherheit: Tage 1, 8, 15 von jedem Zyklus

    Teil II
    • Progressionsfreies Überleben (PFS) nach 6 Monaten und bei Beendigung der Studie
    E.5.2Secondary end point(s)
    Part I
    • Objective response rate (ORR)
    • Progression-free survival (PFS)

    Part II
    • Overall survival (OS),
    • Objective response rate (ORR): best ORR, confirmed ORR
    - Post-progression PFS (PFS II)
    • Patient-reported outcome: EORTC C30, EORTC OV28
    • Safety: AEs (according to NCI CTCAE, version 4.03), laboratory parameters, ECOG PS, vital signs
    • Pharmacokinetics (only in selected sites)
    o evaluate the possible effects of paclitaxel on ganetespib pharmacokinetics
    o evaluate the possible effects of ganetespib on paclitaxel pharmacokinetics
    o quantify ganetespib and ganetespib metabolite exposures in the presence of paclitaxel

    Part II Exploratory endpoints:
    • Molecular efficacy before and during experimental therapy.
    • Biomarker analysis e.g. p53 status on DNA, RNA and protein level
    Teil I
    • Objektive Ansprechrate (ORR)
    • Progressionsfreies Überleben (PFS)

    Teil II
    • Gesamtüberleben (OS),
    • Objektive Ansprechrate (ORR): beste ORR, bestätigte ORR
    - progressionsfreies Überleben nach Progression (PFS II)
    • Patientenfragebögen: EORTC C30, EORTC OV28
    • Sicherheit: AEs (gemessen nach NCI CTCAE, Version 4.03), Laborwerte, ECOG PS, Vitalparameter
    • Pharmacokinetik (nur in ausgewählten Zentren)
    o Auswertung der möglichen Auswirkungen von Paclitaxel auf die Pharmakogenetik von Ganetespib
    o Auswertung der möglichen Auswirkungen von Ganetespib auf die Pharmakogenetik von Paclitaxel
    o Quantifizierung von Ganetespib und Ganetespib-Metabolitenexponierung in der Gegenwart von Paclitaxel

    Teil II Explorative Endpunkte:
    • Molekuläre Wirksamkeit vor und während der experimentellen Therapie.
    • Biomarkeranalyse, z. B. p53-Status auf DNS-, RNS- und Proteinebene
    E.5.2.1Timepoint(s) of evaluation of this end point
    Part I
    • Objective response rate (ORR): at end of trial
    • Progression-free survival (PFS): at 6 months and at end of trial

    Part II
    • Overall survival (OS): at death
    • Objective response rate (ORR), PFS II, Patient-reported outcome, Safety, Pharmacokinetics (only in selected sites): monitored throughout the study but evaluated at end of trial

    Part II Exploratory endpoints:
    • Molecular efficacy before and during experimental therapy and Biomarker analysis e.g. p53 status on DNA, RNA and protein level: at the end of the trial
    Teil I
    • Objektive Ansprechrate (ORR): am Ende der Studie
    • Progressionsfreies Überleben (PFS): nach 6 Monaten und bei Ende der Studie

    Teil II
    • Gesamtüberleben (OS): bei Tod
    • Objektive Ansprechrate (ORR), Patientenfragebögen, Sicherheit, Pharmacokinetik (nur in ausgewählten Zentren): Überwachung während der Studie , aber Auswertung am Ende der Studie

    Teil II Explorative Endpunkte:
    • Molekuläre Wirksamkeit vor und während der experimentellen Therapie, Biomarkeranalyse werden am Ende der Studie ausgewertet
    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 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) Yes
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other Yes
    E.7.1.3.1Other trial type description
    dose escalation/de-escalation
    Erhöhung/Verringerung der Dosis
    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 concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA13
    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 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
    LVLS
    letzte Visite der letzten Patientin
    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 months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years5
    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: 100
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 122
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male No
    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 state19
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 222
    F.4.2.2In the whole clinical trial 222
    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
    keine
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    G.4.1Name of Organisation AGO Austria
    G.4.3.4Network Country Austria
    G.4 Investigator Network to be involved in the Trial: 2
    G.4.1Name of Organisation AGO Germany
    G.4.3.4Network Country Germany
    G.4 Investigator Network to be involved in the Trial: 3
    G.4.1Name of Organisation NOGGO
    G.4.3.4Network Country Germany
    G.4 Investigator Network to be involved in the Trial: 4
    G.4.1Name of Organisation GINECO
    G.4.3.4Network Country France
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2014-03-20
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2014-04-22
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2017-12-04
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2020 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA