Clinical trial NCT01379989: INOVATYON STUDY -International, Randomized Study in Patients With Ovarian Cancer
Official title: Phase III International, Randomized Study of Trabectedin Plus Pegylated Liposomal Doxorubicin (PLD) Versus Carboplatin Plus PLD in Patients With Ovarian Cancer Progressing Within 6-12 Months of Last Platinum
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Ovarian Cancer
Lead sponsor: Mario Negri Institute for Pharmacological Research
Sponsor class: OTHER
Collaborators: name: PharmaMar
name: Averion International Corporation
First posted: 2011-06-23
Enrollment: 617
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Female, aged ≥ 18 years
2. Histologically and/or cytologically proven epithelial ovarian, epithelial fallopian tube cancer or primary peritoneal cancer
3. 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
4. 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.
5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2
6. Estimated life expectancy ≥ 12 weeks
7. Patients must be accessible for treatment and follow-up
8. Adequate organ function within 14 days prior to first cycle as evidenced
9. Patients must be able to receive dexamethasone or its equivalent, which is required if randomly assigned to treatment with trabectedin plus PLD
10. Informed consent of the patient

Exclusion Criteria:

1. Non epithelial ovarian or mixed epithelial/non epithelial tumors (e.g., Mullerian tumors)
2. 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
3. Bowel obstruction, sub-occlusive disease or the presence of symptomatic brain metastases
4. Pre-existing grade \> 1 motor or sensory neuropathy according to the National Cancer Institute Common Toxicity Criteria Adverse Event (NCI-CTCAE) version 4.0
5. 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
6. History of liver disease
7. 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
8. 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)
9. Prior exposure to trabectedin
10. Prior resistance to anthracyclines or PLD defined as a progression during anthracycline-based chemotherapy or a recurrence within 6 months from its ending
11. Prior severe PLD related toxicity
12. Prior exposure to cumulative doses of doxorubicin \>400mg/m2 or epirubicin \>720mg/m2
13. Treatment with any investigational product within 30 days prior to inclusion in the study

Primary outcomes:
measure: Overall survival (OS)
timeFrame: This outcome measure will be assess approximately 4.5-5 years after the last patient enrolled
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: 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
measure: Objective RR
timeFrame: 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
measure: CA-125 serological response
timeFrame: 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
measure: Duration of Response
timeFrame: 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
measure: Time to subsequent chemotherapy administration
timeFrame: 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
measure: OS for Subsequent chemotherapies
timeFrame: 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
measure: PFS for the Subsequent Chemotherapies
timeFrame: 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
measure: Frequency of serious adverse events (SAEs)
timeFrame: 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
measure: QoL according to the EORTC QLQ-C30 and QLQ-OV28
timeFrame: 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
measure: Best response to each Subsequent chemotherapy line
timeFrame: 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
measure: Frequency of toxicities, graded according to the NCI-CTAE version 4.0
timeFrame: 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
measure: Frequency of toxicities leading to dose delays
timeFrame: 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
measure: Frequency of toxicities leading to dose modifications
timeFrame: 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
measure: Frequency of toxicities leading to treatment discontinuation
timeFrame: 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
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Krankenhaus Der Barmherzigen Brueder
state: AT
city: Innsbruck
country: Austria
facility: Univ. Clinic for Gynaecology and Obstetrics - Medical University of Innsbruck
state: AT
city: Graz
country: Austria
facility: Medizinische Universitat Graz
city: Wien
country: Austria
facility: Univ. Klinik Frauenheilkunde AKH
city: Bonheiden
country: Belgium
facility: Imeldaziekenhuis
state: BE
city: Brasschaat
country: Belgium
facility: AZ Klina
state: BE
city: Edegem
country: Belgium
facility: Antwerp University Hospital
state: BE
city: Leuven
country: Belgium
facility: UZ Leuven
state: BE
city: Namur
country: Belgium
facility: CMSE Clinique et Maternité Sainte-Elisabeth
state: BE
city: Oostende
country: Belgium
facility: Az Damiaan
state: BE
city: Turnhout
country: Belgium
facility: Centrum Voor Oncologie
state: BE
city: Verviers
country: Belgium
facility: Centre Hospitalier Peltzer La Tourelle (CHPLT)
state: BE
city: Yvoir
country: Belgium
facility: CHU Dinant Godinne / UCL Namur
state: BE
city: Gent
country: Belgium
facility: AZ Maria Middelares
city: Gent
country: Belgium
facility: UZ Gent
city: Odense
country: Denmark
facility: Odense University Hospital
state: DK
city: Tampere
country: Finland
facility: Tampere University Hospital
state: FI
city: Kuopio
country: Finland
facility: Kuopio University Hospital - Kuopio
city: Oulu
country: Finland
facility: Oulu University Hospital
city: Berlin
country: Germany
facility: Charite Universitaetsmedizin
state: DE
city: Berlin
country: Germany
facility: Ev. Waldkrankenhaus Spandau
state: DE
city: Berlin
country: Germany
facility: Praxis Dr. med. Jörg Schilling
state: DE
city: Berlin
country: Germany
facility: Praxisklinik Krebsheilkunde für Frauen
state: DE
city: Berlin
country: Germany
facility: Vivantes Netzwerk für Gesundheit GmbH
state: DE
city: Dresden
country: Germany
facility: University Hospital Dresden
state: DE
city: Fürstenwalde
country: Germany
facility: Dr. med. Georg Heinrich Schwerpunktpraxis für Gynäkologische Onkologie
state: DE
city: Hamburg
country: Germany
facility: Kath. Marienkrankenhaus
state: DE
city: Heidelberg
country: Germany
facility: Universitäts - Frauenklinik -Tübingen
state: DE
city: Krefeld
country: Germany
facility: Helios Klinikum Krefeld
state: DE
city: Lübeck
country: Germany
facility: "Universitätsklinikum Schleswig-Holstein
state: DE
city: Brandenburg an der Havel
country: Germany
facility: Staedtisches Klinikum Brandenburg
city: Dusseldorf
country: Germany
facility: Universitatsfrauenklinik Dusseldorf
city: Essen
country: Germany
facility: Kliniken Essen Mitte Evang. Huyssens Stiftung
city: Hamburg
country: Germany
facility: University Medical Center Hamburg
city: Jena
country: Germany
facility: Universitaetsklinikum Jena
city: Leverkusen
country: Germany
facility: Klinikum Leverkusen gGmbH
city: Ravensburg
country: Germany
facility: Studienzentrum Onkologie
city: Rostock
country: Germany
facility: UFK am Klinikum Suedstadt Rostock
city: Speyer
country: Germany
facility: Onkologische Schwerpunktpraxis
city: Alessandria
country: Italy
facility: Azienda Ospedaliera SS Antonio e Biagio e Cesare Arrigo
state: AL
city: Aosta
country: Italy
facility: Ospedale Regionale Umberto Parini
state: AO
city: Biella
country: Italy
facility: "Ospedale Degli Infermi - Biella"
state: BI
city: Bologna
country: Italy
facility: Policlinico S.Orsola Malpighi
state: BO
city: Brindisi
country: Italy
facility: P.O. "A.Perrino" ASL Brindisi
state: BR
city: Brescia
country: Italy
facility: A.O. Spedali Civili di Brescia
state: BS
city: Brescia
country: Italy
facility: Fondazione Poliambulanza
state: BS
city: Cuneo
country: Italy
facility: Azienda Ospedaliera S. Croce e Carle
state: CN
city: Como
country: Italy
facility: Ospedale Valduce
state: CO
city: Catania
country: Italy
facility: Azienda Ospedaliero Universitaria "Policlinico- Vittorio Emanuele" P.O. Gaspare Rodolico
state: CT
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) - IRCCS, Meldola e Cesena
state: FC
city: Empoli
country: Italy
facility: Ospedale San Giuseppe - Azienda USL11
state: FI
city: Sora
country: Italy
facility: Ospedale SS Trinità - Sora
state: FR
city: Genova
country: Italy
facility: Ente Ospedaliero Ospedali Galliera
state: GE
city: Genova
country: Italy
facility: IRCCS San Martino IST - Genova
state: GE
city: Lecco
country: Italy
facility: AO della Provincia di Lecco - Ospedale Alessandro Manzoni
state: LC
city: Lecce
country: Italy
facility: Ospedale Vito Fazzi
state: LE
city: Milan
country: Italy
facility: European Institute of Oncology, Department of Surgery Science
state: MI
city: Modena
country: Italy
facility: Azienda Ospedaliero Universitaria Policlinico di Modena
state: MO
city: Palermo
country: Italy
facility: AO Ospedali Riuniti Villa Sofia Cervello
state: PA
city: Piacenza
country: Italy
facility: Ospedale Guglielmo da Saliceto - Piacenza
state: PC
city: Padova
country: Italy
facility: Istituto Oncologico Veneto
state: PD
city: Pisa
country: Italy
facility: Ospedale Santa Chiara
state: PI
city: Prato
country: Italy
facility: Nuovo Ospedale di Prato S. Stefano
state: PO
city: Rionero in Vulture
country: Italy
facility: Istituto di Ricovero e Cura a Carattere Scientifico - Centro Regionale Oncologico Basilicata
state: PZ
city: Faenza
country: Italy
facility: Ospedale di Faenza
state: RA
city: Lugo
country: Italy
facility: Ospedale Umberto I
state: RA
city: Reggio Calabria
country: Italy
facility: Azienda Ospedaliera "Bianchi - Melacrino - Morelli"
state: RC
city: Reggio Emilia
country: Italy
facility: IRCCS - Arcispedale S. Maria Nuova
state: RE
city: Roma
country: Italy
facility: Policlinico Umberto I, Universitàdi Roma "La Sapienza"
state: RM
city: Rimini
country: Italy
facility: Ospedale Infermi
state: RN
city: Sondrio
country: Italy
facility: Ospedale Civile di Sondrio
state: SO
city: Trento
country: Italy
facility: Ospedale di Santa Chiara
state: TN
city: Candiolo
country: Italy
facility: Fondazione Piemontese Per L'Oncologia - IRCCS, Candiolo
state: TO
city: Torino
country: Italy
facility: AOU Città della salute e della scienza - OIRM S. Anna
state: TO
city: Torino
country: Italy
facility: Ospedale Mauriziano
state: TO
city: Torino
country: Italy
facility: Azienda Ospedaliero Universitaria Città Della Salute e Della Scienza di Torino - P.O. S. Anna
state: TO
city: Varese
country: Italy
facility: Ospedale Del Ponte - Varese
state: VA
city: Mirano
country: Italy
facility: U.L.S.S. 13 Mirano - Dolo - Noale
state: VE
city: Negrar
country: Italy
facility: Sacro Cuore Don Calabria
state: VR
city: Catanzaro
country: Italy
facility: AOU Materdomini
city: Napoli
country: Italy
facility: Università degli Studi di Napoli Federico II
city: Novara
country: Italy
facility: AOU Maggiore della Carità
city: Pagani
country: Italy
facility: Presidio Ospedaliero A Tortora
city: Palermo
country: Italy
facility: ARNAS Civico
city: Palermo
country: Italy
facility: Casa di Cura La Maddalena
city: Taormina
country: Italy
facility: Ospedale S. Vincenzo
city: Vercelli
country: Italy
facility: ASL VC Ospedale S. Andrea - Vercelli
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Centre
state: NL
city: Oslo
country: Norway
facility: Radium Hospitalet Oslo University Hospital
city: Stavanger
country: Norway
facility: Stavanger University Hospital
city: Tromsø
country: Norway
facility: University Hospital of North Norway
city: Alicante
country: Spain
facility: Hospital General Universitario de Elche
state: ES
city: Badalona
country: Spain
facility: Hospital Germans Trias I Pujol
state: ES
city: Barcellona
country: Spain
facility: Institut Català d´Oncologia, Hospitalet - Hospitalet de Llobregat
state: ES
city: Castèllo
country: Spain
facility: Consorcio Hospitalario Provincial de Castellon
state: ES
city: Girona
country: Spain
facility: Institut Català d'Oncologia de Girona
state: ES
city: Lleida
country: Spain
facility: H. U. Arnau de Vilanova
state: ES
city: Madrid
country: Spain
facility: MD Anderson Cancer Center
state: ES
city: Manresa
country: Spain
facility: Althaia
state: ES
city: Murcia
country: Spain
facility: Hospital Universitario J.M. Morales Meseguer
state: ES
city: Palma de Mallorca
country: Spain
facility: Hospital Son Espases
state: ES
city: Palma de Mallorca
country: Spain
facility: Hospital Son Llatzer
state: ES
city: Pamplona
country: Spain
facility: Complejo Hospitalario de Navarra
state: ES
city: Sabadell
country: Spain
facility: Corporacion Sanitaria y Universitaria Parc Tauli
state: ES
city: San Sebastian
country: Spain
facility: Hospital Universitario Donostia - San Sebastian
state: ES
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia
state: ES
city: Valencia
country: Spain
facility: Hospital La Fe
state: ES
city: Valencia
country: Spain
facility: IVO Instituto Valenciano de Oncologia
state: ES
city: Cordoba
country: Spain
facility: Hospital Reina Sofia
city: El Palmar
country: Spain
facility: Hospital Clinico Universitario Virgen De La Arrixaca
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Terrassa
country: Spain
facility: Consorci Sanitari De Terrassa
city: Valencia
country: Spain
facility: Hospital Lluis Alcanyis Xativa
city: Valencia
country: Spain
facility: Hospital Universitario Dr Peset
city: Aarau
country: Switzerland
facility: Kantonsspital Aarau
state: CH
city: Basel
country: Switzerland
facility: Frauenklinik -Universitätsspital Basel
state: CH
city: Bern
country: Switzerland
facility: Klinik Engeried
state: CH
city: Bern
country: Switzerland
facility: Universitätsklinik für Frauenheilkunde, Universitätsklinik für Onkologische Medizin - Inselspital
state: CH
city: Chur
country: Switzerland
facility: Kantonsspital Graubünden
state: CH
city: Frauenfeld
country: Switzerland
facility: Kantonsspital Frauenfeld
state: CH
city: Luzern
country: Switzerland
facility: Luzerner Kantonsspital
state: CH
city: Münsterlingen
country: Switzerland
facility: Kantonsspital Münsterlingen
state: CH
city: Olten
country: Switzerland
facility: Kantonsspital Olten
state: CH
city: St. Gallen
country: Switzerland
facility: Kantonsspital St. Gallen
state: CH
city: Winterthur
country: Switzerland
facility: Kantonsspital
state: CH
city: Zürich
country: Switzerland
facility: Frauenklinik - Stadtspital Triemli
state: CH
city: Bellinzona
country: Switzerland
facility: Ospedale Regionale Bellinzona e Valli - Istituto Oncologico Della Svizzera Italiana (IOSI)
state: TI
city: Brighton
country: United Kingdom
facility: Royal Sussex County Hospital
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Center
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
city: Oxford
country: United Kingdom
facility: The Churchill Hospital
city: Worthing
country: United Kingdom
facility: Worthingh Hospital
Study officials:
affiliation: European Institute of Oncology (I.E.O), Milan, Italy
name: Nicoletta Colombo, MD
role: PRINCIPAL_INVESTIGATOR
References: