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

NCT ID: NCT01379989

Last Updated: 2022-02-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 617 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-06-30
• Study Completion Date: 2020-12-17

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.

Conditions

Ovarian Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Carboplatin plus PLD

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

Group Type: ACTIVE_COMPARATOR

Carboplatin

Intervention Type: DRUG

Carboplatin AUC 5

Pegylated Lipoxomal Doxorubicin (PLD)

Intervention Type: DRUG

PLD 30 mg/m² i.v.

Trabectedin plus PLD

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

Group Type: EXPERIMENTAL

Pegylated Lipoxomal Doxorubicin (PLD)

Intervention Type: DRUG

PLD 30 mg/m² i.v.

Trabectedin

Intervention Type: 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.

Interventions

Carboplatin

Carboplatin AUC 5

Intervention Type: DRUG

Pegylated Lipoxomal Doxorubicin (PLD)

PLD 30 mg/m² i.v.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Carboplatin generic; Caelyx; Yondelis

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

PharmaMar

INDUSTRY

Sponsor Role: collaborator

Averion International Corporation

INDUSTRY

Sponsor Role: collaborator

Mario Negri Institute for Pharmacological Research

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nicoletta Colombo, MD

Role: PRINCIPAL_INVESTIGATOR

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

Locations

Krankenhaus Der Barmherzigen Brueder

Graz, AT, Austria

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

Innsbruck, AT, Austria

Medizinische Universitat Graz

Graz, , Austria

Univ. Klinik Frauenheilkunde AKH

Vienna, , Austria

Imeldaziekenhuis

Bonheiden, BE, Belgium

AZ Klina

Brasschaat, BE, Belgium

Antwerp University Hospital

Edegem, BE, Belgium

UZ Leuven

Leuven, BE, Belgium

CMSE Clinique et Maternité Sainte-Elisabeth

Namur, BE, Belgium

Az Damiaan

Ostend, BE, Belgium

Centrum Voor Oncologie

Turnhout, BE, Belgium

Centre Hospitalier Peltzer La Tourelle (CHPLT)

Verviers, BE, Belgium

CHU Dinant Godinne / UCL Namur

Yvoir, BE, Belgium

AZ Maria Middelares

Ghent, , Belgium

UZ Gent

Ghent, , Belgium

Odense University Hospital

Odense, DK, Denmark

Tampere University Hospital

Tampere, FI, Finland

Kuopio University Hospital - Kuopio

Kuopio, , Finland

Oulu University Hospital

Oulu, , Finland

Charite Universitaetsmedizin

Berlin, DE, Germany

Ev. Waldkrankenhaus Spandau

Berlin, DE, Germany

Praxis Dr. med. Jörg Schilling

Berlin, DE, Germany

Praxisklinik Krebsheilkunde für Frauen

Berlin, DE, Germany

Vivantes Netzwerk für Gesundheit GmbH

Berlin, DE, Germany

University Hospital Dresden

Dresden, DE, Germany

Dr. med. Georg Heinrich Schwerpunktpraxis für Gynäkologische Onkologie

Fürstenwalde, DE, Germany

Kath. Marienkrankenhaus

Hamburg, DE, Germany

Universitäts - Frauenklinik -Tübingen

Heidelberg, DE, Germany

Helios Klinikum Krefeld

Krefeld, DE, Germany

"Universitätsklinikum Schleswig-Holstein

Lübeck, DE, Germany

Staedtisches Klinikum Brandenburg

Brandenburg, , Germany

Universitatsfrauenklinik Dusseldorf

Düsseldorf, , Germany

Kliniken Essen Mitte Evang. Huyssens Stiftung

Essen, , Germany

University Medical Center Hamburg

Hamburg, , Germany

Universitaetsklinikum Jena

Jena, , Germany

Klinikum Leverkusen gGmbH

Leverkusen, , Germany

Studienzentrum Onkologie

Ravensburg, , Germany

UFK am Klinikum Suedstadt Rostock

Rostock, , Germany

Onkologische Schwerpunktpraxis

Speyer, , Germany

Azienda Ospedaliera SS Antonio e Biagio e Cesare Arrigo

Alessandria, AL, Italy

Ospedale Regionale Umberto Parini

Aosta, AO, Italy

"Ospedale Degli Infermi - Biella"

Biella, BI, Italy

Policlinico S.Orsola Malpighi

Bologna, BO, Italy

P.O. "A.Perrino" ASL Brindisi

Brindisi, BR, Italy

A.O. Spedali Civili di Brescia

Brescia, BS, Italy

Fondazione Poliambulanza

Brescia, BS, Italy

Azienda Ospedaliera S. Croce e Carle

Cuneo, CN, Italy

Ospedale Valduce

Como, CO, Italy

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

Catania, CT, 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

Ospedale SS Trinità - Sora

Sora, FR, Italy

Ente Ospedaliero Ospedali Galliera

Genova, GE, Italy

IRCCS San Martino IST - Genova

Genova, GE, 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

AO Ospedali Riuniti Villa Sofia Cervello

Palermo, PA, Italy

Ospedale Guglielmo da Saliceto - Piacenza

Piacenza, PC, Italy

Istituto Oncologico Veneto

Padua, PD, Italy

Ospedale Santa Chiara

Pisa, PI, Italy

Nuovo Ospedale di Prato S. Stefano

Prato, PO, Italy

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

Rionero in Vulture, PZ, Italy

Ospedale di Faenza

Faenza, RA, 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

Policlinico Umberto I, Universitàdi Roma "La Sapienza"

Roma, RM, Italy

Ospedale Infermi

Rimini, RN, Italy

Ospedale Civile di Sondrio

Sondrio, SO, Italy

Ospedale di Santa Chiara

Trento, TN, Italy

Fondazione Piemontese Per L'Oncologia - IRCCS, Candiolo

Candiolo, TO, Italy

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

Torino, TO, Italy

Ospedale Mauriziano

Torino, TO, Italy

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

Torino, TO, Italy

Ospedale Del Ponte - Varese

Varese, VA, Italy

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

Mirano, VE, Italy

Sacro Cuore Don Calabria

Negrar, VR, Italy

AOU Materdomini

Catanzaro, , Italy

Università degli Studi di Napoli Federico II

Napoli, , Italy

AOU Maggiore della Carità

Novara, , Italy

Presidio Ospedaliero A Tortora

Pagani, , Italy

ARNAS Civico

Palermo, , Italy

Casa di Cura La Maddalena

Palermo, , Italy

Ospedale S. Vincenzo

Taormina, , Italy

ASL VC Ospedale S. Andrea - Vercelli

Vercelli, , Italy

Radboud University Medical Centre

Nijmegen, NL, Netherlands

Radium Hospitalet Oslo University Hospital

Oslo, , Norway

Stavanger University Hospital

Stavanger, , Norway

University Hospital of North Norway

Tromsø, , Norway

Hospital General Universitario de Elche

Alicante, ES, Spain

Hospital Germans Trias I Pujol

Badalona, ES, Spain

Institut Català d´Oncologia, Hospitalet - Hospitalet de Llobregat

Barcelona, ES, Spain

Consorcio Hospitalario Provincial de Castellon

Castèllo, ES, Spain

Hospital Universitario Donostia - San Sebastian

Donostia / San Sebastian, ES, Spain

Institut Català d'Oncologia de Girona

Girona, ES, Spain

H. U. Arnau de Vilanova

Lleida, ES, Spain

MD Anderson Cancer Center

Madrid, ES, Spain

Althaia

Manresa, ES, Spain

Hospital Universitario J.M. Morales Meseguer

Murcia, ES, Spain

Hospital Son Espases

Palma de Mallorca, ES, Spain

Hospital Son Llatzer

Palma de Mallorca, ES, Spain

Complejo Hospitalario de Navarra

Pamplona, ES, Spain

Corporacion Sanitaria y Universitaria Parc Tauli

Sabadell, ES, Spain

Hospital General Universitario de Valencia

Valencia, ES, Spain

Hospital La Fe

Valencia, ES, Spain

IVO Instituto Valenciano de Oncologia

Valencia, ES, Spain

Hospital Reina Sofia

Córdoba, , Spain

Hospital Clinico Universitario Virgen De La Arrixaca

El Palmar, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Consorci Sanitari De Terrassa

Terrassa, , Spain

Hospital Lluis Alcanyis Xativa

Valencia, , Spain

Hospital Universitario Dr Peset

Valencia, , Spain

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

Bellinzona, Canton Ticino, Switzerland

Kantonsspital Aarau

Aarau, CH, Switzerland

Frauenklinik -Universitätsspital Basel

Basel, CH, Switzerland

Klinik Engeried

Bern, CH, Switzerland

Universitätsklinik für Frauenheilkunde, Universitätsklinik für Onkologische Medizin - Inselspital

Bern, CH, Switzerland

Kantonsspital Graubünden

Chur, CH, Switzerland

Kantonsspital Frauenfeld

Frauenfeld, CH, Switzerland

Luzerner Kantonsspital

Lucerne, CH, Switzerland

Kantonsspital Münsterlingen

Münsterlingen, CH, Switzerland

Kantonsspital Olten

Olten, CH, Switzerland

Kantonsspital St. Gallen

Sankt Gallen, CH, Switzerland

Kantonsspital

Winterthur, CH, Switzerland

Frauenklinik - Stadtspital Triemli

Zurich, CH, Switzerland

Royal Sussex County Hospital

Brighton, , United Kingdom

Velindre Cancer Center

Cardiff, , United Kingdom

Beatson West of Scotland Cancer Centre

Glasgow, , United Kingdom

The Churchill Hospital

Oxford, , United Kingdom

Worthingh Hospital

Worthing, , United Kingdom

Countries

Austria; Belgium; Denmark; Finland; Germany; Italy; Netherlands; Norway; Spain; Switzerland; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 36759720 (View on PubMed)

Other Identifiers

ET-D-009-10

Identifier Type: -

Identifier Source: org_study_id