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

Ovarian Cancer Clinical Trial

— INOVATYON  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01379989
• Other study ID #: ET-D-009-10
• Status: Completed
• Phase: Phase 3
• Start date: June 2011
• Est. completion date: December 17, 2020

Study information

• Verified date: February 2022
• Source: Mario Negri Institute for Pharmacological Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 617
• Est. completion date: December 17, 2020
• Est. primary completion date: December 17, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Ovarian Cancer
• Ovarian Neoplasms

Intervention

Drug:
• Carboplatin
Carboplatin AUC 5
• Pegylated Lipoxomal Doxorubicin (PLD)
PLD 30 mg/m² i.v.
• 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.

Locations

Country	Name	City	State
Austria	Krankenhaus Der Barmherzigen Brueder	Graz	AT
Austria	Medizinische Universitat Graz	Graz
Austria	Univ. Clinic for Gynaecology and Obstetrics - Medical University of Innsbruck	Innsbruck	AT
Austria	Univ. Klinik Frauenheilkunde AKH	Wien
Belgium	Imeldaziekenhuis	Bonheiden	BE
Belgium	AZ Klina	Brasschaat	BE
Belgium	Antwerp University Hospital	Edegem	BE
Belgium	AZ Maria Middelares	Gent
Belgium	UZ Gent	Gent
Belgium	UZ Leuven	Leuven	BE
Belgium	CMSE Clinique et Maternité Sainte-Elisabeth	Namur	BE
Belgium	Az Damiaan	Oostende	BE
Belgium	Centrum Voor Oncologie	Turnhout	BE
Belgium	Centre Hospitalier Peltzer La Tourelle (CHPLT)	Verviers	BE
Belgium	CHU Dinant Godinne / UCL Namur	Yvoir	BE
Denmark	Odense University Hospital	Odense	DK
Finland	Kuopio University Hospital - Kuopio	Kuopio
Finland	Oulu University Hospital	Oulu
Finland	Tampere University Hospital	Tampere	FI
Germany	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	Staedtisches Klinikum Brandenburg	Brandenburg an der Havel
Germany	University Hospital Dresden	Dresden	DE
Germany	Universitatsfrauenklinik Dusseldorf	Dusseldorf
Germany	Kliniken Essen Mitte Evang. Huyssens Stiftung	Essen
Germany	Dr. med. Georg Heinrich Schwerpunktpraxis für Gynäkologische Onkologie	Fürstenwalde	DE
Germany	Kath. Marienkrankenhaus	Hamburg	DE
Germany	University Medical Center Hamburg	Hamburg
Germany	Universitäts - Frauenklinik -Tübingen	Heidelberg	DE
Germany	Universitaetsklinikum Jena	Jena
Germany	Helios Klinikum Krefeld	Krefeld	DE
Germany	Klinikum Leverkusen gGmbH	Leverkusen
Germany	"Universitätsklinikum Schleswig-Holstein	Lübeck	DE
Germany	Studienzentrum Onkologie	Ravensburg
Germany	UFK am Klinikum Suedstadt Rostock	Rostock
Germany	Onkologische Schwerpunktpraxis	Speyer
Italy	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	A.O. Spedali Civili di Brescia	Brescia	BS
Italy	Fondazione Poliambulanza	Brescia	BS
Italy	P.O. "A.Perrino" ASL Brindisi	Brindisi	BR
Italy	Fondazione Piemontese Per L'Oncologia - IRCCS, Candiolo	Candiolo	TO
Italy	Azienda Ospedaliero Universitaria "Policlinico- Vittorio Emanuele" P.O. Gaspare Rodolico	Catania	CT
Italy	AOU Materdomini	Catanzaro
Italy	Ospedale Valduce	Como	CO
Italy	Azienda Ospedaliera S. Croce e Carle	Cuneo	CN
Italy	Ospedale San Giuseppe - Azienda USL11	Empoli	FI
Italy	Ospedale di Faenza	Faenza	RA
Italy	Ente Ospedaliero Ospedali Galliera	Genova	GE
Italy	IRCCS San Martino IST - Genova	Genova	GE
Italy	Ospedale Vito Fazzi	Lecce	LE
Italy	AO della Provincia di Lecco - Ospedale Alessandro Manzoni	Lecco	LC
Italy	Ospedale Umberto I	Lugo	RA
Italy	Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) - IRCCS, Meldola e Cesena	Meldola	FC
Italy	European Institute of Oncology, Department of Surgery Science	Milan	MI
Italy	U.L.S.S. 13 Mirano - Dolo - Noale	Mirano	VE
Italy	Azienda Ospedaliero Universitaria Policlinico di Modena	Modena	MO
Italy	Università degli Studi di Napoli Federico II	Napoli
Italy	Sacro Cuore Don Calabria	Negrar	VR
Italy	AOU Maggiore della Carità	Novara
Italy	Istituto Oncologico Veneto	Padova	PD
Italy	Presidio Ospedaliero A Tortora	Pagani
Italy	AO Ospedali Riuniti Villa Sofia Cervello	Palermo	PA
Italy	ARNAS Civico	Palermo
Italy	Casa di Cura La Maddalena	Palermo
Italy	Ospedale Guglielmo da Saliceto - Piacenza	Piacenza	PC
Italy	Ospedale Santa Chiara	Pisa	PI
Italy	Nuovo Ospedale di Prato S. Stefano	Prato	PO
Italy	Azienda Ospedaliera "Bianchi - Melacrino - Morelli"	Reggio Calabria	RC
Italy	IRCCS - Arcispedale S. Maria Nuova	Reggio Emilia	RE
Italy	Ospedale Infermi	Rimini	RN
Italy	Istituto di Ricovero e Cura a Carattere Scientifico - Centro Regionale Oncologico Basilicata	Rionero in Vulture	PZ
Italy	Policlinico Umberto I, Universitàdi Roma "La Sapienza"	Roma	RM
Italy	Ospedale Civile di Sondrio	Sondrio	SO
Italy	Ospedale SS Trinità - Sora	Sora	FR
Italy	Ospedale S. Vincenzo	Taormina
Italy	AOU Città della salute e della scienza - OIRM S. Anna	Torino	TO
Italy	Azienda Ospedaliero Universitaria Città Della Salute e Della Scienza di Torino - P.O. S. Anna	Torino	TO
Italy	Ospedale Mauriziano	Torino	TO
Italy	Ospedale di Santa Chiara	Trento	TN
Italy	Ospedale Del Ponte - Varese	Varese	VA
Italy	ASL VC Ospedale S. Andrea - Vercelli	Vercelli
Netherlands	Radboud University Medical Centre	Nijmegen	NL
Norway	Radium Hospitalet Oslo University Hospital	Oslo
Norway	Stavanger University Hospital	Stavanger
Norway	University Hospital of North Norway	Tromsø
Spain	Hospital General Universitario de Elche	Alicante	ES
Spain	Hospital Germans Trias I Pujol	Badalona	ES
Spain	Institut Català d´Oncologia, Hospitalet - Hospitalet de Llobregat	Barcellona	ES
Spain	Consorcio Hospitalario Provincial de Castellon	Castèllo	ES
Spain	Hospital Reina Sofia	Cordoba
Spain	Hospital Clinico Universitario Virgen De La Arrixaca	El Palmar
Spain	Institut Català d'Oncologia de Girona	Girona	ES
Spain	H. U. Arnau de Vilanova	Lleida	ES
Spain	Hospital Universitario 12 de Octubre	Madrid
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 Universitario Donostia - San Sebastian	San Sebastian	ES
Spain	Consorci Sanitari De Terrassa	Terrassa
Spain	Hospital General Universitario de Valencia	Valencia	ES
Spain	Hospital La Fe	Valencia	ES
Spain	Hospital Lluis Alcanyis Xativa	Valencia
Spain	Hospital Universitario Dr Peset	Valencia
Spain	IVO Instituto Valenciano de Oncologia	Valencia	ES
Switzerland	Kantonsspital Aarau	Aarau	CH
Switzerland	Frauenklinik -Universitätsspital Basel	Basel	CH
Switzerland	Ospedale Regionale Bellinzona e Valli - Istituto Oncologico Della Svizzera Italiana (IOSI)	Bellinzona	TI
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	Luzern	CH
Switzerland	Kantonsspital Münsterlingen	Münsterlingen	CH
Switzerland	Kantonsspital Olten	Olten	CH
Switzerland	Kantonsspital St. Gallen	St. Gallen	CH
Switzerland	Kantonsspital	Winterthur	CH
Switzerland	Frauenklinik - Stadtspital Triemli	Zürich	CH
United Kingdom	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

Sponsors (3)

Lead Sponsor	Collaborator
Mario Negri Institute for Pharmacological Research	Averion International Corporation, PharmaMar

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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