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

Sponsor
Mario Negri Institute for Pharmacological Research (Other)
Overall Status
Completed
CT.gov ID
NCT01379989
Collaborator
PharmaMar (Industry), Averion International Corporation (Industry)
617
Enrollment
132
Locations
2
Arms
114.6
Duration (Months)
4.7
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

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 Design

Study Type:
Interventional
Actual Enrollment :
617 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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 Start Date :
Jun 1, 2011
Actual Primary Completion Date :
Dec 17, 2020
Actual Study Completion Date :
Dec 17, 2020

Arms and Interventions

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Overall survival (OS) [This outcome measure will be assess approximately 4.5-5 years after the last patient enrolled]

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

    Secondary Outcome Measures

    1. 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]

      PFS will be measured from the date of randomization to the date of documented PD or death (regardless of cause of death).

    2. 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]

      Objective RR will be the best response obtained in any evaluation according to RECIST 1.1

    3. 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]

      CA-125 serological response will be the best response obtained in each arm

    4. 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]

      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.

    5. 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]

      The time from randomization to subsequent chemotherapy counted from the administration of subsequent chemotherapy will be evaluated as an exploratory analysis.

    6. OS for Subsequent chemotherapies [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]

      the overall survival counted from the administration of subsequent chemotherapy until death

    7. PFS for the Subsequent Chemotherapies [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]

      the progression free survival counted from the administration of subsequent chemotherapy untill disease progression or death whichever occurs first

    8. Frequency of serious adverse events (SAEs) [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]

      Number of SAEs for each randomization arm

    9. QoL according to the EORTC QLQ-C30 and QLQ-OV28 [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]

      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.

    10. Best response to each Subsequent chemotherapy line [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]

      The best response obtained to each Subsequent chemotherapy line calculated as frequency of patients with CR, PR, SD or PD.

    11. Frequency of toxicities, graded according to the NCI-CTAE version 4.0 [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]

      Clinical and laboratory toxicities

    12. Frequency of toxicities leading to dose delays [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]

      Clinical and laboratory toxicities

    13. Frequency of toxicities leading to dose modifications [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]

      Clinical and laboratory toxicities

    14. Frequency of toxicities leading to treatment discontinuation [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]

      Clinical and laboratory toxicities

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Krankenhaus Der Barmherzigen Brueder Graz AT Austria 8020
    2 Univ. Clinic for Gynaecology and Obstetrics - Medical University of Innsbruck Innsbruck AT Austria
    3 Medizinische Universitat Graz Graz Austria
    4 Univ. Klinik Frauenheilkunde AKH Wien Austria
    5 Imeldaziekenhuis Bonheiden BE Belgium
    6 AZ Klina Brasschaat BE Belgium
    7 Antwerp University Hospital Edegem BE Belgium
    8 UZ Leuven Leuven BE Belgium
    9 CMSE Clinique et Maternité Sainte-Elisabeth Namur BE Belgium
    10 Az Damiaan Oostende BE Belgium
    11 Centrum Voor Oncologie Turnhout BE Belgium
    12 Centre Hospitalier Peltzer La Tourelle (CHPLT) Verviers BE Belgium
    13 CHU Dinant Godinne / UCL Namur Yvoir BE Belgium
    14 AZ Maria Middelares Gent Belgium
    15 UZ Gent Gent Belgium
    16 Odense University Hospital Odense DK Denmark
    17 Tampere University Hospital Tampere FI Finland 33521
    18 Kuopio University Hospital - Kuopio Kuopio Finland
    19 Oulu University Hospital Oulu Finland
    20 Charite Universitaetsmedizin Berlin DE Germany 10117
    21 Ev. Waldkrankenhaus Spandau Berlin DE Germany
    22 Praxis Dr. med. Jörg Schilling Berlin DE Germany
    23 Praxisklinik Krebsheilkunde für Frauen Berlin DE Germany
    24 Vivantes Netzwerk für Gesundheit GmbH Berlin DE Germany
    25 University Hospital Dresden Dresden DE Germany
    26 Dr. med. Georg Heinrich Schwerpunktpraxis für Gynäkologische Onkologie Fürstenwalde DE Germany
    27 Kath. Marienkrankenhaus Hamburg DE Germany
    28 Universitäts - Frauenklinik -Tübingen Heidelberg DE Germany
    29 Helios Klinikum Krefeld Krefeld DE Germany
    30 "Universitätsklinikum Schleswig-Holstein Lübeck DE Germany
    31 Staedtisches Klinikum Brandenburg Brandenburg an der Havel Germany
    32 Universitatsfrauenklinik Dusseldorf Dusseldorf Germany
    33 Kliniken Essen Mitte Evang. Huyssens Stiftung Essen Germany
    34 University Medical Center Hamburg Hamburg Germany
    35 Universitaetsklinikum Jena Jena Germany
    36 Klinikum Leverkusen gGmbH Leverkusen Germany
    37 Studienzentrum Onkologie Ravensburg Germany
    38 UFK am Klinikum Suedstadt Rostock Rostock Germany
    39 Onkologische Schwerpunktpraxis Speyer Germany
    40 Azienda Ospedaliera SS Antonio e Biagio e Cesare Arrigo Alessandria AL Italy
    41 Ospedale Regionale Umberto Parini Aosta AO Italy
    42 "Ospedale Degli Infermi - Biella" Biella BI Italy
    43 Policlinico S.Orsola Malpighi Bologna BO Italy
    44 P.O. "A.Perrino" ASL Brindisi Brindisi BR Italy
    45 A.O. Spedali Civili di Brescia Brescia BS Italy
    46 Fondazione Poliambulanza Brescia BS Italy
    47 Azienda Ospedaliera S. Croce e Carle Cuneo CN Italy
    48 Ospedale Valduce Como CO Italy
    49 Azienda Ospedaliero Universitaria "Policlinico- Vittorio Emanuele" P.O. Gaspare Rodolico Catania CT Italy
    50 Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) - IRCCS, Meldola e Cesena Meldola FC Italy
    51 Ospedale San Giuseppe - Azienda USL11 Empoli FI Italy
    52 Ospedale SS Trinità - Sora Sora FR Italy
    53 Ente Ospedaliero Ospedali Galliera Genova GE Italy 16128
    54 IRCCS San Martino IST - Genova Genova GE Italy
    55 AO della Provincia di Lecco - Ospedale Alessandro Manzoni Lecco LC Italy
    56 Ospedale Vito Fazzi Lecce LE Italy
    57 European Institute of Oncology, Department of Surgery Science Milan MI Italy 20141
    58 Azienda Ospedaliero Universitaria Policlinico di Modena Modena MO Italy
    59 AO Ospedali Riuniti Villa Sofia Cervello Palermo PA Italy
    60 Ospedale Guglielmo da Saliceto - Piacenza Piacenza PC Italy
    61 Istituto Oncologico Veneto Padova PD Italy 35128
    62 Ospedale Santa Chiara Pisa PI Italy 56126
    63 Nuovo Ospedale di Prato S. Stefano Prato PO Italy
    64 Istituto di Ricovero e Cura a Carattere Scientifico - Centro Regionale Oncologico Basilicata Rionero in Vulture PZ Italy
    65 Ospedale di Faenza Faenza RA Italy
    66 Ospedale Umberto I Lugo RA Italy
    67 Azienda Ospedaliera "Bianchi - Melacrino - Morelli" Reggio Calabria RC Italy
    68 IRCCS - Arcispedale S. Maria Nuova Reggio Emilia RE Italy
    69 Policlinico Umberto I, Universitàdi Roma "La Sapienza" Roma RM Italy
    70 Ospedale Infermi Rimini RN Italy
    71 Ospedale Civile di Sondrio Sondrio SO Italy
    72 Ospedale di Santa Chiara Trento TN Italy
    73 Fondazione Piemontese Per L'Oncologia - IRCCS, Candiolo Candiolo TO Italy
    74 AOU Città della salute e della scienza - OIRM S. Anna Torino TO Italy 10126
    75 Ospedale Mauriziano Torino TO Italy 10128
    76 Azienda Ospedaliero Universitaria Città Della Salute e Della Scienza di Torino - P.O. S. Anna Torino TO Italy
    77 Ospedale Del Ponte - Varese Varese VA Italy
    78 U.L.S.S. 13 Mirano - Dolo - Noale Mirano VE Italy
    79 Sacro Cuore Don Calabria Negrar VR Italy
    80 AOU Materdomini Catanzaro Italy
    81 Università degli Studi di Napoli Federico II Napoli Italy
    82 AOU Maggiore della Carità Novara Italy
    83 Presidio Ospedaliero A Tortora Pagani Italy
    84 ARNAS Civico Palermo Italy
    85 Casa di Cura La Maddalena Palermo Italy
    86 Ospedale S. Vincenzo Taormina Italy
    87 ASL VC Ospedale S. Andrea - Vercelli Vercelli Italy
    88 Radboud University Medical Centre Nijmegen NL Netherlands 6525
    89 Radium Hospitalet Oslo University Hospital Oslo Norway
    90 Stavanger University Hospital Stavanger Norway
    91 University Hospital of North Norway Tromsø Norway
    92 Hospital General Universitario de Elche Alicante ES Spain
    93 Hospital Germans Trias I Pujol Badalona ES Spain 08916
    94 Institut Català d´Oncologia, Hospitalet - Hospitalet de Llobregat Barcellona ES Spain
    95 Consorcio Hospitalario Provincial de Castellon Castèllo ES Spain
    96 Institut Català d'Oncologia de Girona Girona ES Spain
    97 H. U. Arnau de Vilanova Lleida ES Spain 25598
    98 MD Anderson Cancer Center Madrid ES Spain
    99 Althaia Manresa ES Spain
    100 Hospital Universitario J.M. Morales Meseguer Murcia ES Spain
    101 Hospital Son Espases Palma de Mallorca ES Spain
    102 Hospital Son Llatzer Palma de Mallorca ES Spain
    103 Complejo Hospitalario de Navarra Pamplona ES Spain
    104 Corporacion Sanitaria y Universitaria Parc Tauli Sabadell ES Spain
    105 Hospital Universitario Donostia - San Sebastian San Sebastian ES Spain
    106 Hospital General Universitario de Valencia Valencia ES Spain
    107 Hospital La Fe Valencia ES Spain
    108 IVO Instituto Valenciano de Oncologia Valencia ES Spain
    109 Hospital Reina Sofia Cordoba Spain
    110 Hospital Clinico Universitario Virgen De La Arrixaca El Palmar Spain
    111 Hospital Universitario 12 de Octubre Madrid Spain
    112 Consorci Sanitari De Terrassa Terrassa Spain
    113 Hospital Lluis Alcanyis Xativa Valencia Spain
    114 Hospital Universitario Dr Peset Valencia Spain
    115 Kantonsspital Aarau Aarau CH Switzerland
    116 Frauenklinik -Universitätsspital Basel Basel CH Switzerland
    117 Klinik Engeried Bern CH Switzerland
    118 Universitätsklinik für Frauenheilkunde, Universitätsklinik für Onkologische Medizin - Inselspital Bern CH Switzerland
    119 Kantonsspital Graubünden Chur CH Switzerland
    120 Kantonsspital Frauenfeld Frauenfeld CH Switzerland
    121 Luzerner Kantonsspital Luzern CH Switzerland
    122 Kantonsspital Münsterlingen Münsterlingen CH Switzerland
    123 Kantonsspital Olten Olten CH Switzerland
    124 Kantonsspital St. Gallen St. Gallen CH Switzerland
    125 Kantonsspital Winterthur CH Switzerland
    126 Frauenklinik - Stadtspital Triemli Zürich CH Switzerland
    127 Ospedale Regionale Bellinzona e Valli - Istituto Oncologico Della Svizzera Italiana (IOSI) Bellinzona TI Switzerland
    128 Royal Sussex County Hospital Brighton United Kingdom
    129 Velindre Cancer Center Cardiff United Kingdom
    130 Beatson West of Scotland Cancer Centre Glasgow United Kingdom
    131 The Churchill Hospital Oxford United Kingdom
    132 Worthingh Hospital Worthing United Kingdom

    Sponsors and Collaborators

    • Mario Negri Institute for Pharmacological Research
    • PharmaMar
    • Averion International Corporation

    Investigators

    • Principal Investigator: Nicoletta Colombo, MD, European Institute of Oncology (I.E.O), Milan, Italy

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Mario Negri Institute for Pharmacological Research
    ClinicalTrials.gov Identifier:
    NCT01379989
    Other Study ID Numbers:
    • ET-D-009-10
    First Posted:
    Jun 23, 2011
    Last Update Posted:
    Feb 9, 2022
    Last Verified:
    Feb 1, 2022
    Additional relevant MeSH terms:
    Ovarian Neoplasms
    Carcinoma, Ovarian Epithelial
    Carboplatin
    Doxorubicin
    Trabectedin

    Study Results

    No Results Posted as of Feb 9, 2022