Clinical trial NCT00326456: MITO-2: A Study Comparing 2 Chemotherapy Regimens (Carboplatin/Liposomal Doxorubicin vs Carboplatin/Paclitaxel) in Patients With Ovarian Cancer
Official title: Phase III Randomized Multicentre Trial of Carboplatin + Liposomal Doxorubicin vs Carboplatin + Paclitaxel in Patients With Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Ovarian Cancer
Keywords: ovarian cancer
chemotherapy
first-line
Lead sponsor: National Cancer Institute, Naples
Sponsor class: OTHER
First posted: 2006-05-16
Enrollment: 820
Sex: FEMALE
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare the effectiveness (progression free survival) of the experimental combination of carboplatin + liposomal doxorubicin with the standard combination of carboplatin + paclitaxel in first line treatment of patients with ovarian cancer.

Secondary objectives are to evaluate overall survival, quality of life, objective response rate, and toxicity.

Detailed description: Ovarian cancer is the second most frequent and the most deadly gynaecologic cancer. The high mortality rate is due to the late diagnosis of this malignancy that often develops without symptoms, as well as to limited results in treatment of the disease. Patients may respond well initially to chemotherapy, but the vast majority of patients will experience a progression of the disease. The poor long term results in the standard treatment available today for first-line chemotherapy of ovarian cancer make research into new, more beneficial treatment strategies necessary. The proven efficacy of liposomal doxorubicin in second line treatment, where it is the first drug to have shown some significant benefit in terms of survival, and the possibility of easily combining it with full doses and normal use of carboplatin, encourages the testing of the effectiveness of the combination of carboplatin and liposomal doxorubicin in first line treatment.

Patients enrolled into this study will be randomly assigned to one of two treatment groups:

· Standard therapy consisting of 6 cycles of chemotherapy:

* carboplatin AUC 5 given intravenously on day 1 every 3 weeks AND
* paclitaxel 175 mg/m2 given intravenously on day 1 every 3 weeks

OR

· Experimental therapy consisting of 6 cycles of chemotherapy:

* carboplatin AUC 5 given intravenously on day 1 every 3 weeks AND
* liposomal doxorubicin 30 mg/m2 given intravenously on day 1 every 3 weeks

Eligibility criteria: Inclusion Criteria:

* Cytologic / histologic diagnosis of stage Ic-IV ovarian cancer
* Indication for chemotherapy treatment
* Age 75 years or less
* Life expectancy of at least 3 months

Exclusion Criteria:

* Previous or concomitant malignant neoplasia (not including basocellular or spinocellular skin carcinoma or in-situ carcinoma of the uterine cervix, provided they are being adequately treated)
* Performance status (ECOG) \> 2
* Previous chemotherapy treatment
* Heart disease (heart failure, myocardial heart attack within 6 months prior to randomization, atrioventricular block of any degree, serious arrhythmia)
* Leukocytes \< 4000/mm3, neutrophils \< 2000/mm3, platelets \< 100000/mm3
* Impaired renal function (creatinine \> 1.25 times the upper normal limit) or liver function (SGOT or SGPT \> 1.25 times the upper normal limit)
* Present or suspected hemorrhagic syndromes
* Uncooperative and/or unreliable patients
* Patient's inability to access the center
* Refusal of informed consent

Primary outcomes:
measure: Progression free survival
timeFrame: at 2 years
Secondary outcomes:
measure: overall survival
timeFrame: 4 years
measure: quality of life
timeFrame: at baseline and every 3 weeks during treatment
measure: objective response rate
timeFrame: at 9 and 18 weeks after starting study therapy
measure: adverse events
timeFrame: every 3 weeks during chemotherapy
Other outcomes:
Locations:
city: Avellino
country: Italy
facility: Clinica Malzoni, Reparto di Ginecologia Oncologica
state: AV
city: Monteforte Irpino
country: Italy
facility: Azienda Ospedaliera S. Giuseppe Moscati, U.O. di Oncologia Medica
state: AV
city: Acquaviva delle Fonti
country: Italy
facility: Ospedale Regionale Miulli, Divisione Medicina Interna Sezione Oncologica
state: BA
city: Bari
country: Italy
facility: IRCCS Oncologico Bari, Oncologia Medica
state: BA
city: Bari
country: Italy
facility: Istituto Oncologico di Bari, U.O. di Oncologia Medica e Sperimentale
state: BA
city: Bergamo
country: Italy
facility: Ospedale Riuniti di Bergamo, U.O. di Ostetricia e Ginecologia
state: BG
city: Benevento
country: Italy
facility: Ospedale Fatebenefratelli, U.O. di Oncologia
state: BN
city: Bentivoglio
country: Italy
facility: Ospedale di Bentivoglio
state: BO
city: Bologna
country: Italy
facility: Ospedale Bellari, U.O. di Oncologia
state: BO
city: Budrio
country: Italy
facility: Ospedale di Budrio
state: BO
city: Cagliari
country: Italy
facility: Policlinico Universitario, Oncologia Medica II
state: CA
city: Campobasso
country: Italy
facility: Università Cattolica del Sacro Cuore, Dipartimento di Oncologia
state: CB
city: Cosenza
country: Italy
facility: Ospedale Mariano Santo, U.O. di Oncologia Medica
state: CS
city: Catania
country: Italy
facility: Ospedale Cannizzaro, Divisione di Ostetricia e Ginecologia
state: CT
city: Ferrara
country: Italy
facility: Azienda Ospedaliera Universitaria Acrispedale Sant'Anna
state: FE
city: Forli'
country: Italy
facility: Ospedale Pierantoni, Divisione di Oncologia Medica
state: FO
city: Mantova
country: Italy
facility: Azienda Ospedaliera Carlo Poma, Divisione di Oncologia ed Ematologia
state: MN
city: Carpi
country: Italy
facility: Ospedale Ramazzini, Day Hospital Oncologico
state: MO
city: Palermo
country: Italy
facility: Policlinico Universitario P. Giaccone
state: PA
city: Palermo
country: Italy
facility: Ospedale M. Ascoli
state: PA
city: Palermo
country: Italy
facility: Casa di Cura La Maddalena S.p.A., Dipartimento Oncologico
state: PA
city: Penne
country: Italy
facility: Ospedale S. Massimo, Day Hospital Oncologico
state: PE
city: Aviano
country: Italy
facility: Centro di Riferimento Oncologico, Divisione di Oncolgia Medica C
state: PN
city: Pordenone
country: Italy
facility: Azienda Ospedaliera S. Maria degli Angeli, Servizio di Oncologia
state: PN
city: Faenza
country: Italy
facility: Ospedale Civile di Faenza, Divisione di Oncologia Medica
state: RA
city: Reggio Calabria
country: Italy
facility: Azienda Ospedaliera Bianchi Melacrino Morelli Ospedale Riuniti, Divisione di Oncologia Medica
state: RE
city: Rimini
country: Italy
facility: Ospedale degli Infermi, U.O. Oncologia Medica
state: RI
city: Nocera Inferiore
country: Italy
facility: Ospedale Civile Umberto I, Day Hospital Oncoematologico
state: SA
city: Trento
country: Italy
facility: Ospedale S. Chiara, U.O. di Oncologia Medica
state: TN
city: Torino
country: Italy
facility: Ospedale S. Anna, Day Hospital Oncologico Divisione A
state: TO
city: Vicenza
country: Italy
facility: Ospedale S. Bortolo ULSS 6, U.O. di Oncologia Medica
state: VI
city: Napoli
country: Italy
facility: Azienda Ospedaliera D. Cotugno
city: Napoli
country: Italy
facility: Istituto Nazionale dei Tumori , Divisione di Oncologia Medica B
city: Napoli
country: Italy
facility: Istituto Nazionale dei Tumori, Divisione di Oncologia Medica C
city: Roma
country: Italy
facility: Istituto Regina Elena, Divisione di Oncologia Medica
city: Roma
country: Italy
facility: Ospedale S. Giovanni Calibita Gatebenefratelli
city: Coimbra
country: Portugal
facility: CHC Maternidade Bissaya-Barreto, Gynecology Unit
city: Istanbul
country: Turkey
facility: Istanbul University Medical Oncology
Study officials:
affiliation: National Cancer Institute, Naples
name: Sandro Pignata, M.D., Ph.D
role: PRINCIPAL_INVESTIGATOR
affiliation: National Cancer Institute, Naples
name: Francesco Perrone, M.D., Ph.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pignata S, Scambia G, Savarese A, Breda E, Scollo P, De Vivo R, Rossi E, Gebbia V, Natale D, Del Gaizo F, Naglieri E, Ferro A, Musso P, D'Arco AM, Sorio R, Pisano C, Di Maio M, Signoriello G, Annunziata A, Perrone F; MITO Investigators. Safety of a 3-weekly schedule of carboplatin plus pegylated liposomal doxorubicin as first line chemotherapy in patients with ovarian cancer: preliminary results of the MITO-2 randomized trial. BMC Cancer. 2006 Aug 1;6:202. doi: 10.1186/1471-2407-6-202.
citation: Pignata S, Scambia G, Savarese A, Breda E, Sorio R, Pisano C, Lorusso D, Cognetti F, Vernaglia Lombardi A, Gebbia V, Scollo P, Morabito A, Signoriello G, Perrone F. Carboplatin and pegylated liposomal doxorubicin for advanced ovarian cancer: preliminary activity results of the MITO-2 phase III trial. Oncology. 2009;76(1):49-54. doi: 10.1159/000178760. Epub 2008 Nov 27.
citation: Pignata S, Scambia G, Ferrandina G, Savarese A, Sorio R, Breda E, Gebbia V, Musso P, Frigerio L, Del Medico P, Lombardi AV, Febbraro A, Scollo P, Ferro A, Tamberi S, Brandes A, Ravaioli A, Valerio MR, Aitini E, Natale D, Scaltriti L, Greggi S, Pisano C, Lorusso D, Salutari V, Legge F, Di Maio M, Morabito A, Gallo C, Perrone F. Carboplatin plus paclitaxel versus carboplatin plus pegylated liposomal doxorubicin as first-line treatment for patients with ovarian cancer: the MITO-2 randomized phase III trial. J Clin Oncol. 2011 Sep 20;29(27):3628-35. doi: 10.1200/JCO.2010.33.8566. Epub 2011 Aug 15.