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

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

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.

Study Overview

• Status: Completed
• Conditions: Ovarian Cancer
• Intervention / Treatment: Drug: Carboplatin; Drug: Pegylated Lipoxomal Doxorubicin (PLD); Drug: Trabectedin

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.

• Study Type: Interventional
• Enrollment (Actual): 617
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria
    • Medizinische Universitat Graz
  • Wien, Austria
    • Univ. Klinik Frauenheilkunde AKH
  • AT
    • Graz, AT, Austria, 8020
      • Krankenhaus Der Barmherzigen Brueder
    • Innsbruck, AT, Austria
      • Univ. Clinic for Gynaecology and Obstetrics - Medical University of Innsbruck
• Belgium
  • Gent, Belgium
    • UZ Gent
  • Gent, Belgium
    • AZ Maria Middelares
  • BE
    • Bonheiden, BE, Belgium
      • Imeldaziekenhuis
    • Brasschaat, BE, Belgium
      • AZ Klina
    • Edegem, BE, Belgium
      • Antwerp University Hospital
    • Leuven, BE, Belgium
      • UZ Leuven
    • Namur, BE, Belgium
      • CMSE Clinique et Maternité Sainte-Elisabeth
    • Oostende, BE, Belgium
      • AZ Damiaan
    • Turnhout, BE, Belgium
      • Centrum Voor Oncologie
    • Verviers, BE, Belgium
      • Centre Hospitalier Peltzer La Tourelle (CHPLT)
    • Yvoir, BE, Belgium
      • CHU Dinant Godinne / UcL Namur
• Denmark
  • DK
    • Odense, DK, Denmark
      • Odense University Hospital
• Finland
  • Kuopio, Finland
    • Kuopio University Hospital - Kuopio
  • Oulu, Finland
    • Oulu University Hospital
  • FI
    • Tampere, FI, Finland, 33521
      • Tampere University Hospital
• Germany
  • Brandenburg an der Havel, Germany
    • Staedtisches Klinikum Brandenburg
  • Dusseldorf, Germany
    • Universitätsfrauenklinik Düsseldorf
  • Essen, Germany
    • Kliniken Essen Mitte Evang. Huyssens Stiftung
  • Hamburg, Germany
    • University Medical Center Hamburg
  • Jena, Germany
    • Universitaetsklinikum Jena
  • Leverkusen, Germany
    • Klinikum Leverkusen gGmbH
  • Ravensburg, Germany
    • Studienzentrum Onkologie
  • Rostock, Germany
    • UFK am Klinikum Suedstadt Rostock
  • Speyer, Germany
    • Onkologische Schwerpunktpraxis
  • DE
    • Berlin, DE, Germany, 10117
      • Charite Universitaetsmedizin
    • Berlin, DE, Germany
      • Ev. Waldkrankenhaus Spandau
    • Berlin, DE, Germany
      • Praxis Dr. med. Jörg Schilling
    • Berlin, DE, Germany
      • Praxisklinik Krebsheilkunde fur Frauen
    • Berlin, DE, Germany
      • Vivantes Netzwerk für Gesundheit GmbH
    • Dresden, DE, Germany
      • University Hospital Dresden
    • Fürstenwalde, DE, Germany
      • Dr. med. Georg Heinrich Schwerpunktpraxis für Gynäkologische Onkologie
    • Hamburg, DE, Germany
      • Kath. Marienkrankenhaus
    • Heidelberg, DE, Germany
      • Universitäts - Frauenklinik -Tübingen
    • Krefeld, DE, Germany
      • Helios Klinikum Krefeld
    • Lübeck, DE, Germany
      • "Universitätsklinikum Schleswig-Holstein
• Italy
  • Catanzaro, Italy
    • AOU Materdomini
  • Napoli, Italy
    • Università Degli Studi Di Napoli Federico Ii
  • Novara, Italy
    • AOU Maggiore della Carità
  • Pagani, Italy
    • Presidio Ospedaliero A Tortora
  • Palermo, Italy
    • Casa di Cura La Maddalena
  • Palermo, Italy
    • ARNAS Civico
  • Taormina, Italy
    • Ospedale S. Vincenzo
  • Vercelli, Italy
    • ASL VC Ospedale S. Andrea - Vercelli
  • AL
    • Alessandria, AL, Italy
      • Azienda Ospedaliera SS Antonio e Biagio e Cesare Arrigo
  • AO
    • Aosta, AO, Italy
      • Ospedale Regionale Umberto Parini
  • BI
    • Biella, BI, Italy
      • "Ospedale Degli Infermi - Biella"
  • BO
    • Bologna, BO, Italy
      • Policlinico S.Orsola Malpighi
  • BR
    • Brindisi, BR, Italy
      • P.O. "A.Perrino" ASL Brindisi
  • BS
    • Brescia, BS, Italy
      • A.O. Spedali Civili di Brescia
    • Brescia, BS, Italy
      • Fondazione Poliambulanza
  • CN
    • Cuneo, CN, Italy
      • Azienda Ospedaliera S. Croce e Carle
  • CO
    • Como, CO, Italy
      • Ospedale Valduce
  • CT
    • Catania, CT, Italy
      • Azienda Ospedaliero Universitaria "Policlinico- Vittorio Emanuele" P.O. Gaspare Rodolico
  • FC
    • Meldola, FC, Italy
      • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) - IRCCS, Meldola e Cesena
  • FI
    • Empoli, FI, Italy
      • Ospedale San Giuseppe - Azienda USL11
  • FR
    • Sora, FR, Italy
      • Ospedale SS Trinità - Sora
  • GE
    • Genova, GE, Italy, 16128
      • Ente Ospedaliero Ospedali Galliera
    • Genova, GE, Italy
      • IRCCS San Martino IST - Genova
  • LC
    • Lecco, LC, Italy
      • AO della Provincia di Lecco - Ospedale Alessandro Manzoni
  • LE
    • Lecce, LE, Italy
      • Ospedale Vito Fazzi
  • MI
    • Milan, MI, Italy, 20141
      • European Institute of Oncology, Department of Surgery Science
  • MO
    • Modena, MO, Italy
      • Azienda Ospedaliero Universitaria Policlinico di Modena
  • PA
    • Palermo, PA, Italy
      • AO Ospedali Riuniti Villa Sofia Cervello
  • PC
    • Piacenza, PC, Italy
      • Ospedale Guglielmo da Saliceto - Piacenza
  • PD
    • Padova, PD, Italy, 35128
      • Istituto Oncologico Veneto
  • PI
    • Pisa, PI, Italy, 56126
      • Ospedale Santa Chiara
  • PO
    • Prato, PO, Italy
      • Nuovo Ospedale di Prato S. Stefano
  • PZ
    • Rionero in Vulture, PZ, Italy
      • Istituto di Ricovero e Cura a Carattere Scientifico - Centro Regionale Oncologico Basilicata
  • RA
    • Faenza, RA, Italy
      • Ospedale Di Faenza
    • Lugo, RA, Italy
      • Ospedale Umberto I
  • RC
    • Reggio Calabria, RC, Italy
      • Azienda Ospedaliera "Bianchi - Melacrino - Morelli"
  • RE
    • Reggio Emilia, RE, Italy
      • IRCCS - Arcispedale S. Maria Nuova
  • RM
    • Roma, RM, Italy
      • Policlinico Umberto I, Universitàdi Roma "La Sapienza"
  • RN
    • Rimini, RN, Italy
      • Ospedale Infermi
  • SO
    • Sondrio, SO, Italy
      • Ospedale Civile Di Sondrio
  • TN
    • Trento, TN, Italy
      • Ospedale di Santa Chiara
  • TO
    • Candiolo, TO, Italy
      • Fondazione Piemontese Per L'Oncologia - IRCCS, Candiolo
    • Torino, TO, Italy, 10126
      • AOU Città della salute e della scienza - OIRM S. Anna
    • Torino, TO, Italy, 10128
      • Ospedale Mauriziano
    • Torino, TO, Italy
      • Azienda Ospedaliero Universitaria Città Della Salute e Della Scienza di Torino - P.O. S. Anna
  • VA
    • Varese, VA, Italy
      • Ospedale Del Ponte - Varese
  • VE
    • Mirano, VE, Italy
      • U.L.S.S. 13 Mirano - Dolo - Noale
  • VR
    • Negrar, VR, Italy
      • Sacro Cuore Don Calabria
• Netherlands
  • NL
    • Nijmegen, NL, Netherlands, 6525
      • Radboud University Medical Centre
• Norway
  • Oslo, Norway
    • Radium Hospitalet Oslo University Hospital
  • Stavanger, Norway
    • Stavanger University Hospital
  • Tromsø, Norway
    • University Hospital of North Norway
• Spain
  • Cordoba, Spain
    • Hospital Reina Sofia
  • El Palmar, Spain
    • Hospital Clinico Universitario Virgen de la Arrixaca
  • Madrid, Spain
    • Hospital Universitario 12 de Octubre
  • Terrassa, Spain
    • Consorci Sanitari de Terrassa
  • Valencia, Spain
    • Hospital Universitario Dr Peset
  • Valencia, Spain
    • Hospital Lluis Alcanyis Xativa
  • ES
    • Alicante, ES, Spain
      • Hospital General Universitario de Elche
    • Badalona, ES, Spain, 08916
      • Hospital Germans Trias i Pujol
    • Barcellona, ES, Spain
      • Institut Català d´Oncologia, Hospitalet - Hospitalet de Llobregat
    • Castèllo, ES, Spain
      • Consorcio Hospitalario Provincial de Castellon
    • Girona, ES, Spain
      • Institut Catala d'Oncologia de Girona
    • Lleida, ES, Spain, 25598
      • H. U. Arnau de Vilanova
    • Madrid, ES, Spain
      • MD Anderson Cancer Center
    • Manresa, ES, Spain
      • Althaia
    • Murcia, ES, Spain
      • Hospital Universitario J.M. Morales Meseguer
    • Palma de Mallorca, ES, Spain
      • Hospital Son Espases
    • Palma de Mallorca, ES, Spain
      • Hospital Son Llàtzer
    • Pamplona, ES, Spain
      • Complejo Hospitalario de Navarra
    • Sabadell, ES, Spain
      • Corporacion Sanitaria y Universitaria Parc Tauli
    • San Sebastian, ES, Spain
      • Hospital Universitario Donostia - San Sebastian
    • Valencia, ES, Spain
      • Hospital General Universitario de Valencia
    • Valencia, ES, Spain
      • Hospital la Fé
    • Valencia, ES, Spain
      • IVO Instituto Valenciano de Oncología
• Switzerland
  • CH
    • Aarau, CH, Switzerland
      • Kantonsspital Aarau
    • Basel, CH, Switzerland
      • Frauenklinik -Universitätsspital Basel
    • Bern, CH, Switzerland
      • Klinik Engeried
    • Bern, CH, Switzerland
      • Universitätsklinik für Frauenheilkunde, Universitätsklinik für Onkologische Medizin - Inselspital
    • Chur, CH, Switzerland
      • Kantonsspital Graubunden
    • Frauenfeld, CH, Switzerland
      • Kantonsspital Frauenfeld
    • Luzern, CH, Switzerland
      • Luzerner Kantonsspital
    • Münsterlingen, CH, Switzerland
      • Kantonsspital Münsterlingen
    • Olten, CH, Switzerland
      • Kantonsspital Olten
    • St. Gallen, CH, Switzerland
      • Kantonsspital St. Gallen
    • Winterthur, CH, Switzerland
      • Kantonsspital
    • Zürich, CH, Switzerland
      • Frauenklinik - Stadtspital Triemli
  • TI
    • Bellinzona, TI, Switzerland
      • Ospedale Regionale Bellinzona e Valli - Istituto Oncologico Della Svizzera Italiana (IOSI)
• United Kingdom
  • Brighton, United Kingdom
    • Royal Sussex County Hospital
  • Cardiff, United Kingdom
    • Velindre Cancer Center
  • Glasgow, United Kingdom
    • Beatson West Of Scotland Cancer Centre
  • Oxford, United Kingdom
    • The Churchill Hospital
  • Worthing, United Kingdom
    • Worthingh Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Carboplatin plus PLD; Pegylated Lipoxomal Doxorubicin (PLD) 30 mg/ m2 followed by carboplatin AUC 5.	Drug: Carboplatin; Carboplatin AUC 5; Other Names: Carboplatin generic; Drug: Pegylated Lipoxomal Doxorubicin (PLD); PLD 30 mg/m² i.v.; Other Names: Caelyx
Experimental: Trabectedin plus PLD; Pegylated Lipoxomal Doxorubicin (PLD) 30 mg/m2 infusion followed by trabectedin 1.1 mg/m2 infusion.	Drug: Pegylated Lipoxomal Doxorubicin (PLD); PLD 30 mg/m² i.v.; Other Names: Caelyx; Drug: Trabectedin; 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.; Other Names: Yondelis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	PFS will be measured from the date of randomization to the date of documented PD or death (regardless of cause of death).	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	Objective RR will be the best response obtained in any evaluation according to RECIST 1.1	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	CA-125 serological response will be the best response obtained in each arm	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	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.	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	The time from randomization to subsequent chemotherapy counted from the administration of subsequent chemotherapy will be evaluated as an exploratory analysis.	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
OS for Subsequent chemotherapies	the overall survival counted from the administration of subsequent chemotherapy until death	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 for the Subsequent Chemotherapies	the progression free survival counted from the administration of subsequent chemotherapy untill disease progression or death whichever occurs first	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
Frequency of serious adverse events (SAEs)	Number of SAEs for each randomization arm	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
QoL according to the EORTC QLQ-C30 and QLQ-OV28	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.	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
Best response to each Subsequent chemotherapy line	The best response obtained to each Subsequent chemotherapy line calculated as frequency of patients with CR, PR, SD or PD.	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
Frequency of toxicities, graded according to the NCI-CTAE version 4.0	Clinical and laboratory toxicities	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
Frequency of toxicities leading to dose delays	Clinical and laboratory toxicities	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
Frequency of toxicities leading to dose modifications	Clinical and laboratory toxicities	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
Frequency of toxicities leading to treatment discontinuation	Clinical and laboratory toxicities	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

Collaborators and Investigators

• Sponsor: Mario Negri Institute for Pharmacological Research
• Collaborators: PharmaMar; Averion International Corporation
• Investigators: Principal Investigator: Nicoletta Colombo, MD, European Institute of Oncology (I.E.O), Milan, Italy

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): December 17, 2020
• Study Completion (Actual): December 17, 2020

Study Registration Dates

• First Submitted: June 1, 2011
• First Submitted That Met QC Criteria: June 22, 2011
• First Posted (Estimate): June 23, 2011

Study Record Updates

• Last Update Posted (Actual): February 9, 2022
• Last Update Submitted That Met QC Criteria: February 8, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Carboplatin; Doxorubicin; Trabectedin
• Other Study ID Numbers: ET-D-009-10