INOVATYON STUDY -International, Randomized Study in Patients With Ovarian Cancer
- Conditions
- Ovarian Cancer
- Interventions
- Registration Number
- NCT01379989
- Lead Sponsor
- Mario Negri Institute for Pharmacological Research
- Brief Summary
The objective of this multicentric, randomised, Phase III study is to demonstrate superiority, in terms of survival, of trabectedin and Pegylated Liposomal Doxorubicin (PLD) versus carboplatin and PLD in partially-platinum sensitive ovarian cancer patients.
- Detailed Description
Patients will be randomised to:
Arm A: PLD 30 mg/m2 and carboplatin AUC 5; Arm B: PLD 30 mg/m2 and trabectedin 1.1 mg/m2. Patients' characteristics: patients over 18 years of age with advanced, progressive ovarian cancer 6-12 months after completion of first line or second line treatment with platinum-based chemotherapy.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 617
- Female, aged ≥ 18 years
- Histologically and/or cytologically proven epithelial ovarian, epithelial fallopian tube cancer or primary peritoneal cancer
- Progression free interval between six and twelve (6-12) months (calculated from the first day of the last cycle of the last platinum-based chemotherapy until the date of progression confirmation through radiologic imagery). Patients may have received up to two platinum-based chemotherapy lines, of which at least one must have contained a taxane
- Measurable or evaluable disease confirmed by radiological imaging, such as magnetic resonance imaging (MRI), computed tomography (CT) scan, or PET/CT scan at study entry (CA-125 rise not supported by radiological evidence of disease is not accepted as criteria for defining progression) or histological proven recurrent ovarian cancer even in the absence of postoperatively measurable or evaluable lesions.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2
- Estimated life expectancy ≥ 12 weeks
- Patients must be accessible for treatment and follow-up
- Adequate organ function within 14 days prior to first cycle as evidenced
- Patients must be able to receive dexamethasone or its equivalent, which is required if randomly assigned to treatment with trabectedin plus PLD
- Informed consent of the patient
- Non epithelial ovarian or mixed epithelial/non epithelial tumors (e.g., Mullerian tumors)
- Patients who did not respond to last platinum-based therapy or in whom last relapse occurred < 6 months or > 12 months from the last dose of platinum
- Bowel obstruction, sub-occlusive disease or the presence of symptomatic brain metastases
- Pre-existing grade > 1 motor or sensory neuropathy according to the National Cancer Institute Common Toxicity Criteria Adverse Event (NCI-CTCAE) version 4.0
- Myocardial infarct within six months before enrolment, New York Association (NYHA) Class II or worse heart failure (Appendix 1. The New York Heart Association), uncontrolled angina, severe uncontrolled ventricular arrythmias, clinically significant pericardial disease, or electrocardiographic evidence of acute ischemic or active conduction system abnormalities
- History of liver disease
- Concurrent severe medical problems or any unstable medical condition unrelated to malignancy, which would significantly limit full compliance with the study or expose the patient to extreme risk or decreased life expectancy
- Breastfeeding women and women of child bearing potential must use effective contraception during treatment and 3 months thereafter, which may include prescription contraceptives (oral, injection, or patch), intrauterine device, double-barrier method or male partner sterilization (not applicable to patients that are surgically sterile)
- Prior exposure to trabectedin
- Prior resistance to anthracyclines or PLD defined as a progression during anthracycline-based chemotherapy or a recurrence within 6 months from its ending
- Prior severe PLD related toxicity
- Prior exposure to cumulative doses of doxorubicin >400mg/m2 or epirubicin >720mg/m2
- Treatment with any investigational product within 30 days prior to inclusion in the study
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Carboplatin plus PLD Pegylated Lipoxomal Doxorubicin (PLD) Pegylated Lipoxomal Doxorubicin (PLD) 30 mg/ m2 followed by carboplatin AUC 5. Carboplatin plus PLD Carboplatin Pegylated Lipoxomal Doxorubicin (PLD) 30 mg/ m2 followed by carboplatin AUC 5. Trabectedin plus PLD Pegylated Lipoxomal Doxorubicin (PLD) Pegylated Lipoxomal Doxorubicin (PLD) 30 mg/m2 infusion followed by trabectedin 1.1 mg/m2 infusion. Trabectedin plus PLD Trabectedin Pegylated Lipoxomal Doxorubicin (PLD) 30 mg/m2 infusion followed by trabectedin 1.1 mg/m2 infusion.
- Primary Outcome Measures
Name Time Method Overall survival (OS) This outcome measure will be assess approximately 4.5-5 years after the last patient enrolled This is an event driven study. The study will continue until 442 events have occurred.
- Secondary Outcome Measures
Name Time Method Time to subsequent chemotherapy administration This outcome measure will be assess approximately 4.5-5 years after the last patient enrolled, at the same time points of the Primary Endpoint The time from randomization to subsequent chemotherapy counted from the administration of subsequent chemotherapy will be evaluated as an exploratory analysis.
CA-125 serological response This outcome measure will be assess approximately 4.5-5 years after the last patient enrolled, at the same time points of the Primary Endpoint CA-125 serological response will be the best response obtained in each arm
OS for Subsequent chemotherapies This outcome measure will be assess approximately 4.5-5 years after the last patient enrolled, at the same time points of the Primary Endpoint the overall survival counted from the administration of subsequent chemotherapy until death
Best response to each Subsequent chemotherapy line This outcome measure will be assess approximately 4.5-5 years after the last patient enrolled, at the same time points of the Primary Endpoint The best response obtained to each Subsequent chemotherapy line calculated as frequency of patients with CR, PR, SD or PD.
Duration of Response This outcome measure will be assess approximately 4.5-5 years after the last patient enrolled, at the same time points of the Primary Endpoint Duration of response: will be calculated from the date of first documentation of response (CR or partial response \[PR\], whichever occurs first) to the date of documented PD or death.
Progression Free Survival (PFS) This outcome measure will be assess approximately 4.5-5 years after the last patient enrolled, at the same time points of the Primary Endpoint PFS will be measured from the date of randomization to the date of documented PD or death (regardless of cause of death).
Objective RR This outcome measure will be assess approximately 4.5-5 years after the last patient enrolled, at the same time points of the Primary Endpoint Objective RR will be the best response obtained in any evaluation according to RECIST 1.1
PFS for the Subsequent Chemotherapies This outcome measure will be assess approximately 4.5-5 years after the last patient enrolled, at the same time points of the Primary Endpoint the progression free survival counted from the administration of subsequent chemotherapy untill disease progression or death whichever occurs first
Frequency of serious adverse events (SAEs) This outcome measure will be assess approximately 4.5-5 years after the last patient enrolled, at the same time points of the Primary Endpoint Number of SAEs for each randomization arm
QoL according to the EORTC QLQ-C30 and QLQ-OV28 This outcome measure will be assess approximately 4.5-5 years after the last patient enrolled, at the same time points of the Primary Endpoint Two PRO instruments will be administered in this study: the EORTC QLQ-C30 and QLQ-OV28.PRO instruments will be completed by the patient at screening (before randomization) and within four weeks after the 6th cycle or at the time of progression, whichever occurs first.
Frequency of toxicities leading to dose delays This outcome measure will be assess approximately 4.5-5 years after the last patient enrolled, at the same time points of the Primary Endpoint Clinical and laboratory toxicities
Frequency of toxicities, graded according to the NCI-CTAE version 4.0 This outcome measure will be assess approximately 4.5-5 years after the last patient enrolled, at the same time points of the Primary Endpoint Clinical and laboratory toxicities
Frequency of toxicities leading to treatment discontinuation This outcome measure will be assess approximately 4.5-5 years after the last patient enrolled, at the same time points of the Primary Endpoint Clinical and laboratory toxicities
Frequency of toxicities leading to dose modifications This outcome measure will be assess approximately 4.5-5 years after the last patient enrolled, at the same time points of the Primary Endpoint Clinical and laboratory toxicities
Trial Locations
- Locations (132)
Medizinische Universitat Graz
🇦🇹Graz, Austria
Radboud University Medical Centre
🇳🇱Nijmegen, NL, Netherlands
Stavanger University Hospital
🇳🇴Stavanger, Norway
CMSE Clinique et Maternité Sainte-Elisabeth
🇧🇪Namur, BE, Belgium
Oulu University Hospital
🇫🇮Oulu, Finland
Kantonsspital
🇨🇭Winterthur, CH, Switzerland
University Hospital of North Norway
🇳🇴Tromsø, Norway
Kantonsspital Aarau
🇨🇭Aarau, CH, Switzerland
AZ Klina
🇧🇪Brasschaat, BE, Belgium
Antwerp University Hospital
🇧🇪Edegem, BE, Belgium
Centrum Voor Oncologie
🇧🇪Turnhout, BE, Belgium
Kuopio University Hospital - Kuopio
🇫🇮Kuopio, Finland
Ospedale Regionale Bellinzona e Valli - Istituto Oncologico Della Svizzera Italiana (IOSI)
🇨🇭Bellinzona, TI, Switzerland
Univ. Clinic for Gynaecology and Obstetrics - Medical University of Innsbruck
🇦🇹Innsbruck, AT, Austria
Imeldaziekenhuis
🇧🇪Bonheiden, BE, Belgium
Centre Hospitalier Peltzer La Tourelle (CHPLT)
🇧🇪Verviers, BE, Belgium
UZ Gent
🇧🇪Gent, Belgium
Tampere University Hospital
🇫🇮Tampere, FI, Finland
Radium Hospitalet Oslo University Hospital
🇳🇴Oslo, Norway
Klinik Engeried
🇨🇭Bern, CH, Switzerland
Kantonsspital Graubünden
🇨🇭Chur, CH, Switzerland
Universitätsklinik für Frauenheilkunde, Universitätsklinik für Onkologische Medizin - Inselspital
🇨🇭Bern, CH, Switzerland
Policlinico S.Orsola Malpighi
🇮🇹Bologna, BO, Italy
Azienda Ospedaliera S. Croce e Carle
🇮🇹Cuneo, CN, Italy
Ospedale SS Trinità - Sora
🇮🇹Sora, FR, Italy
AO della Provincia di Lecco - Ospedale Alessandro Manzoni
🇮🇹Lecco, LC, Italy
Ospedale Vito Fazzi
🇮🇹Lecce, LE, Italy
European Institute of Oncology, Department of Surgery Science
🇮🇹Milan, MI, Italy
Azienda Ospedaliero Universitaria Policlinico di Modena
🇮🇹Modena, MO, Italy
Ospedale Guglielmo da Saliceto - Piacenza
🇮🇹Piacenza, PC, Italy
Istituto Oncologico Veneto
🇮🇹Padova, PD, Italy
Istituto di Ricovero e Cura a Carattere Scientifico - Centro Regionale Oncologico Basilicata
🇮🇹Rionero in Vulture, PZ, Italy
AO Ospedali Riuniti Villa Sofia Cervello
🇮🇹Palermo, PA, Italy
U.L.S.S. 13 Mirano - Dolo - Noale
🇮🇹Mirano, VE, Italy
ASL VC Ospedale S. Andrea - Vercelli
🇮🇹Vercelli, Italy
Krankenhaus Der Barmherzigen Brueder
🇦🇹Graz, AT, Austria
Ospedale Regionale Umberto Parini
🇮🇹Aosta, AO, Italy
P.O. "A.Perrino" ASL Brindisi
🇮🇹Brindisi, BR, Italy
University Hospital Dresden
🇩🇪Dresden, DE, Germany
Kliniken Essen Mitte Evang. Huyssens Stiftung
🇩🇪Essen, Germany
University Medical Center Hamburg
🇩🇪Hamburg, Germany
Universitatsfrauenklinik Dusseldorf
🇩🇪Dusseldorf, Germany
Helios Klinikum Krefeld
🇩🇪Krefeld, DE, Germany
"Universitätsklinikum Schleswig-Holstein
🇩🇪Lübeck, DE, Germany
Charite Universitaetsmedizin
🇩🇪Berlin, DE, Germany
CHU Dinant Godinne / UCL Namur
🇧🇪Yvoir, BE, Belgium
Odense University Hospital
🇩🇰Odense, DK, Denmark
Praxis Dr. med. Jörg Schilling
🇩🇪Berlin, DE, Germany
Azienda Ospedaliera SS Antonio e Biagio e Cesare Arrigo
🇮🇹Alessandria, AL, Italy
"Ospedale Degli Infermi - Biella"
🇮🇹Biella, BI, Italy
Vivantes Netzwerk für Gesundheit GmbH
🇩🇪Berlin, DE, Germany
Universitäts - Frauenklinik -Tübingen
🇩🇪Heidelberg, DE, Germany
Universitaetsklinikum Jena
🇩🇪Jena, Germany
UFK am Klinikum Suedstadt Rostock
🇩🇪Rostock, Germany
Kath. Marienkrankenhaus
🇩🇪Hamburg, DE, Germany
Studienzentrum Onkologie
🇩🇪Ravensburg, Germany
A.O. Spedali Civili di Brescia
🇮🇹Brescia, BS, Italy
Fondazione Poliambulanza
🇮🇹Brescia, BS, Italy
Ospedale Valduce
🇮🇹Como, CO, Italy
Azienda Ospedaliero Universitaria "Policlinico- Vittorio Emanuele" P.O. Gaspare Rodolico
🇮🇹Catania, CT, Italy
Hospital General Universitario de Valencia
🇪🇸Valencia, ES, Spain
Hospital Universitario Donostia - San Sebastian
🇪🇸San Sebastian, ES, Spain
Complejo Hospitalario de Navarra
🇪🇸Pamplona, ES, Spain
Ospedale Santa Chiara
🇮🇹Pisa, PI, Italy
Nuovo Ospedale di Prato S. Stefano
🇮🇹Prato, PO, Italy
Ospedale Infermi
🇮🇹Rimini, RN, Italy
AOU Città della salute e della scienza - OIRM S. Anna
🇮🇹Torino, TO, Italy
Ospedale Del Ponte - Varese
🇮🇹Varese, VA, Italy
ARNAS Civico
🇮🇹Palermo, Italy
Ospedale S. Vincenzo
🇮🇹Taormina, Italy
Ospedale Umberto I
🇮🇹Lugo, RA, Italy
Azienda Ospedaliera "Bianchi - Melacrino - Morelli"
🇮🇹Reggio Calabria, RC, Italy
IRCCS - Arcispedale S. Maria Nuova
🇮🇹Reggio Emilia, RE, Italy
Ospedale Civile di Sondrio
🇮🇹Sondrio, SO, Italy
Fondazione Piemontese Per L'Oncologia - IRCCS, Candiolo
🇮🇹Candiolo, TO, Italy
Ospedale Mauriziano
🇮🇹Torino, TO, Italy
AOU Maggiore della Carità
🇮🇹Novara, Italy
Presidio Ospedaliero A Tortora
🇮🇹Pagani, Italy
Policlinico Umberto I, Universitàdi Roma "La Sapienza"
🇮🇹Roma, RM, Italy
Ospedale di Santa Chiara
🇮🇹Trento, TN, Italy
Azienda Ospedaliero Universitaria Città Della Salute e Della Scienza di Torino - P.O. S. Anna
🇮🇹Torino, TO, Italy
Sacro Cuore Don Calabria
🇮🇹Negrar, VR, Italy
AOU Materdomini
🇮🇹Catanzaro, Italy
Università degli Studi di Napoli Federico II
🇮🇹Napoli, Italy
Casa di Cura La Maddalena
🇮🇹Palermo, Italy
Corporacion Sanitaria y Universitaria Parc Tauli
🇪🇸Sabadell, ES, Spain
Hospital Son Espases
🇪🇸Palma de Mallorca, ES, Spain
Hospital Son Llatzer
🇪🇸Palma de Mallorca, ES, Spain
Hospital Germans Trias I Pujol
🇪🇸Badalona, ES, Spain
H. U. Arnau de Vilanova
🇪🇸Lleida, ES, Spain
Consorcio Hospitalario Provincial de Castellon
🇪🇸Castèllo, ES, Spain
Institut Català d'Oncologia de Girona
🇪🇸Girona, ES, Spain
Consorci Sanitari De Terrassa
🇪🇸Terrassa, Spain
Frauenklinik -Universitätsspital Basel
🇨🇭Basel, CH, Switzerland
Luzerner Kantonsspital
🇨🇭Luzern, CH, Switzerland
Royal Sussex County Hospital
🇬🇧Brighton, United Kingdom
The Churchill Hospital
🇬🇧Oxford, United Kingdom
Worthingh Hospital
🇬🇧Worthing, United Kingdom
Kantonsspital Frauenfeld
🇨🇭Frauenfeld, CH, Switzerland
Kantonsspital Münsterlingen
🇨🇭Münsterlingen, CH, Switzerland
Frauenklinik - Stadtspital Triemli
🇨🇭Zürich, CH, Switzerland
Kantonsspital Olten
🇨🇭Olten, CH, Switzerland
MD Anderson Cancer Center
🇪🇸Madrid, ES, Spain
Althaia
🇪🇸Manresa, ES, Spain
Hospital Reina Sofia
🇪🇸Cordoba, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Lluis Alcanyis Xativa
🇪🇸Valencia, Spain
Hospital La Fe
🇪🇸Valencia, ES, Spain
Hospital Universitario Dr Peset
🇪🇸Valencia, Spain
Klinikum Leverkusen gGmbH
🇩🇪Leverkusen, Germany
Onkologische Schwerpunktpraxis
🇩🇪Speyer, Germany
Univ. Klinik Frauenheilkunde AKH
🇦🇹Wien, Austria
UZ Leuven
🇧🇪Leuven, BE, Belgium
Az Damiaan
🇧🇪Oostende, BE, Belgium
Ev. Waldkrankenhaus Spandau
🇩🇪Berlin, DE, Germany
AZ Maria Middelares
🇧🇪Gent, Belgium
Praxisklinik Krebsheilkunde für Frauen
🇩🇪Berlin, DE, Germany
Staedtisches Klinikum Brandenburg
🇩🇪Brandenburg an der Havel, Germany
Dr. med. Georg Heinrich Schwerpunktpraxis für Gynäkologische Onkologie
🇩🇪Fürstenwalde, DE, Germany
Ente Ospedaliero Ospedali Galliera
🇮🇹Genova, GE, Italy
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) - IRCCS, Meldola e Cesena
🇮🇹Meldola, FC, Italy
Ospedale San Giuseppe - Azienda USL11
🇮🇹Empoli, FI, Italy
IRCCS San Martino IST - Genova
🇮🇹Genova, GE, Italy
Ospedale di Faenza
🇮🇹Faenza, RA, Italy
Institut Català d´Oncologia, Hospitalet - Hospitalet de Llobregat
🇪🇸Barcellona, ES, Spain
Hospital Universitario J.M. Morales Meseguer
🇪🇸Murcia, ES, Spain
Hospital General Universitario de Elche
🇪🇸Alicante, ES, Spain
IVO Instituto Valenciano de Oncologia
🇪🇸Valencia, ES, Spain
Hospital Clinico Universitario Virgen De La Arrixaca
🇪🇸El Palmar, Spain
Beatson West of Scotland Cancer Centre
🇬🇧Glasgow, United Kingdom
Kantonsspital St. Gallen
🇨🇭St. Gallen, CH, Switzerland
Velindre Cancer Center
🇬🇧Cardiff, United Kingdom