INOVATYON STUDY -International, Randomized Study in Patients With Ovarian Cancer

NCT01379989 | Completed Phase 3 DMC

• 1 other identifier: ET-D-009-10
• Study Type: interventional
• Target: 617
• Locations: 11 countries
• Sites: 132

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.

Conditions

Ovarian Cancer

Outcome Measures

Primary Outcomes (1)

• Overall survival (OS)

  This is an event driven study. The study will continue until 442 events have occurred.

  This outcome measure will be assess approximately 4.5-5 years after the last patient enrolled

Secondary Outcomes (14)

• 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

• 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

• 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

• 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

• 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

Study Arms (2)

Carboplatin plus PLD

ACTIVE COMPARATOR

Pegylated Lipoxomal Doxorubicin (PLD) 30 mg/ m2 followed by carboplatin AUC 5.

Drug: Carboplatin; Drug: Pegylated Lipoxomal Doxorubicin (PLD)

Trabectedin plus PLD

EXPERIMENTAL

Pegylated Lipoxomal Doxorubicin (PLD) 30 mg/m2 infusion followed by trabectedin 1.1 mg/m2 infusion.

Drug: Pegylated Lipoxomal Doxorubicin (PLD); Drug: Trabectedin

Interventions

Carboplatin DRUG

Carboplatin AUC 5

Also known as: Carboplatin generic

Carboplatin plus PLD

Pegylated Lipoxomal Doxorubicin (PLD) DRUG

PLD 30 mg/m² i.v.

Also known as: Caelyx

Carboplatin plus PLD; Trabectedin plus PLD

Trabectedin DRUG

trabectedin 1.1 mg/m2 3-hour i.v. infusion on Day 1 every 3 weeks. The use of central venous access is strongly recommended.

Also known as: Yondelis

Trabectedin plus PLD

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mario Negri Institute for Pharmacological Research: lead
• PharmaMar: collaborator
• Averion International Corporation: collaborator

Study Sites (132)

Krankenhaus Der Barmherzigen Brueder

Graz, AT, 8020, Austria

Location

Univ. Clinic for Gynaecology and Obstetrics - Medical University of Innsbruck

Innsbruck, AT, Austria

Location

Medizinische Universitat Graz

Graz, Austria

Location

Univ. Klinik Frauenheilkunde AKH

Vienna, Austria

Location

Imeldaziekenhuis

Bonheiden, BE, Belgium

Location

AZ Klina

Brasschaat, BE, Belgium

Location

Antwerp University Hospital

Edegem, BE, Belgium

Location

UZ Leuven

Leuven, BE, Belgium

Location

CMSE Clinique et Maternité Sainte-Elisabeth

Namur, BE, Belgium

Location

Az Damiaan

Ostend, BE, Belgium

Location

Centrum Voor Oncologie

Turnhout, BE, Belgium

Location

Centre Hospitalier Peltzer La Tourelle (CHPLT)

Verviers, BE, Belgium

Location

CHU Dinant Godinne / UCL Namur

Yvoir, BE, Belgium

Location

AZ Maria Middelares

Ghent, Belgium

Location

UZ Gent

Ghent, Belgium

Location

Odense University Hospital

Odense, DK, Denmark

Location

Tampere University Hospital

Tampere, FI, 33521, Finland

Location

Kuopio University Hospital - Kuopio

Kuopio, Finland

Location

Oulu University Hospital

Oulu, Finland

Location

Charite Universitaetsmedizin

Berlin, DE, 10117, Germany

Location

Ev. Waldkrankenhaus Spandau

Berlin, DE, Germany

Location

Praxis Dr. med. Jörg Schilling

Berlin, DE, Germany

Location

Praxisklinik Krebsheilkunde für Frauen

Berlin, DE, Germany

Location

Vivantes Netzwerk für Gesundheit GmbH

Berlin, DE, Germany

Location

University Hospital Dresden

Dresden, DE, Germany

Location

Dr. med. Georg Heinrich Schwerpunktpraxis für Gynäkologische Onkologie

Fürstenwalde, DE, Germany

Location

Kath. Marienkrankenhaus

Hamburg, DE, Germany

Location

Universitäts - Frauenklinik -Tübingen

Heidelberg, DE, Germany

Location

Helios Klinikum Krefeld

Krefeld, DE, Germany

Location

"Universitätsklinikum Schleswig-Holstein

Lübeck, DE, Germany

Location

Staedtisches Klinikum Brandenburg

Brandenburg, Germany

Location

Universitatsfrauenklinik Dusseldorf

Düsseldorf, Germany

Location

Kliniken Essen Mitte Evang. Huyssens Stiftung

Essen, Germany

Location

University Medical Center Hamburg

Hamburg, Germany

Location

Universitaetsklinikum Jena

Jena, Germany

Location

Klinikum Leverkusen gGmbH

Leverkusen, Germany

Location

Studienzentrum Onkologie

Ravensburg, Germany

Location

UFK am Klinikum Suedstadt Rostock

Rostock, Germany

Location

Onkologische Schwerpunktpraxis

Speyer, Germany

Location

Azienda Ospedaliera SS Antonio e Biagio e Cesare Arrigo

Alessandria, AL, Italy

Location

Ospedale Regionale Umberto Parini

Aosta, AO, Italy

Location

"Ospedale Degli Infermi - Biella"

Biella, BI, Italy

Location

Policlinico S.Orsola Malpighi

Bologna, BO, Italy

Location

P.O. "A.Perrino" ASL Brindisi

Brindisi, BR, Italy

Location

A.O. Spedali Civili di Brescia

Brescia, BS, Italy

Location

Fondazione Poliambulanza

Brescia, BS, Italy

Location

Azienda Ospedaliera S. Croce e Carle

Cuneo, CN, Italy

Location

Ospedale Valduce

Como, CO, Italy

Location

Azienda Ospedaliero Universitaria "Policlinico- Vittorio Emanuele" P.O. Gaspare Rodolico

Catania, CT, Italy

Location

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) - IRCCS, Meldola e Cesena

Meldola, FC, Italy

Location

Ospedale San Giuseppe - Azienda USL11

Empoli, FI, Italy

Location

Ospedale SS Trinità - Sora

Sora, FR, Italy

Location

Ente Ospedaliero Ospedali Galliera

Genova, GE, 16128, Italy

Location

IRCCS San Martino IST - Genova

Genova, GE, Italy

Location

AO della Provincia di Lecco - Ospedale Alessandro Manzoni

Lecco, LC, Italy

Location

Ospedale Vito Fazzi

Lecce, LE, Italy

Location

European Institute of Oncology, Department of Surgery Science

Milan, MI, 20141, Italy

Location

Azienda Ospedaliero Universitaria Policlinico di Modena

Modena, MO, Italy

Location

AO Ospedali Riuniti Villa Sofia Cervello

Palermo, PA, Italy

Location

Ospedale Guglielmo da Saliceto - Piacenza

Piacenza, PC, Italy

Location

Istituto Oncologico Veneto

Padua, PD, 35128, Italy

Location

Ospedale Santa Chiara

Pisa, PI, 56126, Italy

Location

Nuovo Ospedale di Prato S. Stefano

Prato, PO, Italy

Location

Istituto di Ricovero e Cura a Carattere Scientifico - Centro Regionale Oncologico Basilicata

Rionero in Vulture, PZ, Italy

Location

Ospedale di Faenza

Faenza, RA, Italy

Location

Ospedale Umberto I

Lugo, RA, Italy

Location

Azienda Ospedaliera "Bianchi - Melacrino - Morelli"

Reggio Calabria, RC, Italy

Location

IRCCS - Arcispedale S. Maria Nuova

Reggio Emilia, RE, Italy

Location

Policlinico Umberto I, Universitàdi Roma "La Sapienza"

Roma, RM, Italy

Location

Ospedale Infermi

Rimini, RN, Italy

Location

Ospedale Civile di Sondrio

Sondrio, SO, Italy

Location

Ospedale di Santa Chiara

Trento, TN, Italy

Location

Fondazione Piemontese Per L'Oncologia - IRCCS, Candiolo

Candiolo, TO, Italy

Location

AOU Città della salute e della scienza - OIRM S. Anna

Torino, TO, 10126, Italy

Location

Ospedale Mauriziano

Torino, TO, 10128, Italy

Location

Azienda Ospedaliero Universitaria Città Della Salute e Della Scienza di Torino - P.O. S. Anna

Torino, TO, Italy

Location

Ospedale Del Ponte - Varese

Varese, VA, Italy

Location

U.L.S.S. 13 Mirano - Dolo - Noale

Mirano, VE, Italy

Location

Sacro Cuore Don Calabria

Negrar, VR, Italy

Location

AOU Materdomini

Catanzaro, Italy

Location

Università degli Studi di Napoli Federico II

Napoli, Italy

Location

AOU Maggiore della Carità

Novara, Italy

Location

Presidio Ospedaliero A Tortora

Pagani, Italy

Location

ARNAS Civico

Palermo, Italy

Location

Casa di Cura La Maddalena

Palermo, Italy

Location

Ospedale S. Vincenzo

Taormina, Italy

Location

ASL VC Ospedale S. Andrea - Vercelli

Vercelli, Italy

Location

Radboud University Medical Centre

Nijmegen, NL, 6525, Netherlands

Location

Radium Hospitalet Oslo University Hospital

Oslo, Norway

Location

Stavanger University Hospital

Stavanger, Norway

Location

University Hospital of North Norway

Tromsø, Norway

Location

Hospital General Universitario de Elche

Alicante, ES, Spain

Location

Hospital Germans Trias I Pujol

Badalona, ES, 08916, Spain

Location

Institut Català d´Oncologia, Hospitalet - Hospitalet de Llobregat

Barcelona, ES, Spain

Location

Consorcio Hospitalario Provincial de Castellon

Castèllo, ES, Spain

Location

Hospital Universitario Donostia - San Sebastian

Donostia / San Sebastian, ES, Spain

Location

Institut Català d'Oncologia de Girona

Girona, ES, Spain

Location

H. U. Arnau de Vilanova

Lleida, ES, 25598, Spain

Location

MD Anderson Cancer Center

Madrid, ES, Spain

Location

Althaia

Manresa, ES, Spain

Location

Hospital Universitario J.M. Morales Meseguer

Murcia, ES, Spain

Location

Hospital Son Espases

Palma de Mallorca, ES, Spain

Location

Hospital Son Llatzer

Palma de Mallorca, ES, Spain

Location

Complejo Hospitalario de Navarra

Pamplona, ES, Spain

Location

Corporacion Sanitaria y Universitaria Parc Tauli

Sabadell, ES, Spain

Location

Hospital General Universitario de Valencia

Valencia, ES, Spain

Location

Hospital La Fe

Valencia, ES, Spain

Location

IVO Instituto Valenciano de Oncologia

Valencia, ES, Spain

Location

Hospital Reina Sofia

Córdoba, Spain

Location

Hospital Clinico Universitario Virgen De La Arrixaca

El Palmar, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

Consorci Sanitari De Terrassa

Terrassa, Spain

Location

Hospital Lluis Alcanyis Xativa

Valencia, Spain

Location

Hospital Universitario Dr Peset

Valencia, Spain

Location

Ospedale Regionale Bellinzona e Valli - Istituto Oncologico Della Svizzera Italiana (IOSI)

Bellinzona, Canton Ticino, Switzerland

Location

Kantonsspital Aarau

Aarau, CH, Switzerland

Location

Frauenklinik -Universitätsspital Basel

Basel, CH, Switzerland

Location

Klinik Engeried

Bern, CH, Switzerland

Location

Universitätsklinik für Frauenheilkunde, Universitätsklinik für Onkologische Medizin - Inselspital

Bern, CH, Switzerland

Location

Kantonsspital Graubünden

Chur, CH, Switzerland

Location

Kantonsspital Frauenfeld

Frauenfeld, CH, Switzerland

Location

Luzerner Kantonsspital

Lucerne, CH, Switzerland

Location

Kantonsspital Münsterlingen

Münsterlingen, CH, Switzerland

Location

Kantonsspital Olten

Olten, CH, Switzerland

Location

Kantonsspital St. Gallen

Sankt Gallen, CH, Switzerland

Location

Kantonsspital

Winterthur, CH, Switzerland

Location

Frauenklinik - Stadtspital Triemli

Zurich, CH, Switzerland

Location

Royal Sussex County Hospital

Brighton, United Kingdom

Location

Velindre Cancer Center

Cardiff, United Kingdom

Location

Beatson West of Scotland Cancer Centre

Glasgow, United Kingdom

Location

The Churchill Hospital

Oxford, United Kingdom

Location

Worthingh Hospital

Worthing, United Kingdom

Location

Related Publications (1)

• Colombo N, Gadducci A, Sehouli J, Rulli E, Maenpaa J, Sessa C, Montes A, Ottevanger NB, Berger R, Vergote I, D'Incalci M, Churruca Galaz C, Chekerov R, Nyvang GB, Riniker S, Herbertson R, Fossati R, Barretina-Ginesta MP, Deryal M, Mirza MR, Biagioli E, Iglesias M, Funari G, Romeo M, Tasca G, Pardo B, Tognon G, Rubio-Perez MJ, DeCensi A, De Giorgi U, Zola P, Benedetti Panici P, Aglietta M, Arcangeli V, Zamagni C, Bologna A, Westermann A, Heinzelmann-Schwarz V, Tsibulak I, Wimberger P, Poveda A; INOVATYON study group. INOVATYON/ ENGOT-ov5 study: Randomized phase III international study comparing trabectedin/pegylated liposomal doxorubicin (PLD) followed by platinum at progression vs carboplatin/PLD in patients with recurrent ovarian cancer progressing within 6-12 months after last platinum line. Br J Cancer. 2023 Apr;128(8):1503-1513. doi: 10.1038/s41416-022-02108-7. Epub 2023 Feb 9.

  PMID: 36759720 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

Carboplatin; liposomal doxorubicin; Trabectedin

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Dioxoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrahydroisoquinolines; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Nicoletta Colombo, MD

  European Institute of Oncology (I.E.O), Milan, Italy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2011
• First Posted: June 23, 2011
• Study Start: June 1, 2011
• Primary Completion: December 17, 2020
• Study Completion: December 17, 2020
• Last Updated: February 9, 2022

Record last verified: 2022-02

Locations

FI (3); NL (1); NO (3); AU (4); IT (48); ES (23); CH (13); DK (1); DE (20); GB (5); BE (11)