MITO-2: A Study Comparing 2 Chemotherapy Regimens (Carboplatin/Liposomal Doxorubicin vs Carboplatin/Paclitaxel) in Patients With Ovarian Cancer

Phase III Randomized Multicentre Trial of Carboplatin + Liposomal Doxorubicin vs Carboplatin + Paclitaxel in Patients With Ovarian Cancer

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.

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

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