Efficacy Study of Chemotherapy to Treat Ovarian Cancer Recurrence by Prolonging the Platinum Free Interval

Liposomal Doxorubicin Versus Carboplatin/Paclitaxel in Patients With Ovarian Cancer Recurrence Between 6 and 12 Months After Previous Platinum Based Therapy: Phase III Randomized Multicenter Study Amendment Title Protocol Version 2.0: Phase III International Multicenter Randomized Study Testing the Effect on Survival of Prolonging Platinum-free Interval in Patients With Ovarian Cancer Recurring Between 6 and 12 Months After Previous Platinum Based Chemotherapy.

This study aims to test the hypothesis that the artificial prolongation of the platinum-free interval with a non-platinum treatment will improve the effectiveness of overall therapy in patients with ovarian cancer progression occurring 6-12 months after first-line treatment with a platinum-derivative.

Ovarian cancer is the most deadly gynecologic cancer. Though many patients respond well initially to chemotherapy, most of them in time will suffer a relapse. Patients often receive multiple lines of chemotherapy for their recurrences, and the choice of chemotherapy depends largely on the time interval since the last therapy. Patients whose disease recurs longer than 12 months after a platinum containing treatment are considered to be platinum sensitive, and are candidates for retreatment with a platinum regimen.

Patients in whom disease recurs less than 6 months after a platinum containing treatment are considered platinum resistant or refractory, and are treated with a non platinum chemotherapy. The option of treatment is less clear for patients whose disease recurs between 6 and 12 months after platinum containing therapy. It is hypothesized that prolonging the interval since last platinum treatment by using a non platinum chemotherapy will result in better outcomes for these patients.

This study will evaluate if the experimental sequence of a non platinum based chemotherapy, followed at a later progression by a platinum based chemotherapy is superior, in terms of the effect on overall survival, to the standard inverse sequence of treatment.

Inclusion Criteria:

• Histological or cytological diagnosis of ovarian cancer
• Disease recurrence between 6 and 12 months after a first-line platinum based therapy
• Indication for chemotherapy, but no more than 2 previous lines of previous therapy
• Life expectancy of more than 3 months

Exclusion Criteria:

• Previous or concomitant malignant malignancy (excluding adequately treated baso-or squamocellular carcinoma of the skin and carcinoma in situ of the cervix)
• ECOG Performance Status at least 3
• Previous treatment with stealth liposomal doxorubicin
• Residual peripheral neuropathy Grade 3 or higher
• Heart disease (congestive heart failure, myocardial infarction within 6 months from study entry, atrioventricular block of any grade, severe arrhythmias)
• Neutrophils < 2000 x mm3, platelets < 100000 x mm3
• Inadequate renal function (creatinine no greater than 1.25 x normal values) or liver function (ALT or AST no greater than 1.25 x normal values)
• Present or suspected hemorrhagic syndromes
• Inability to comply with protocol and follow-up
• Inability to access study site for clinical visits
• Refusal of informed consent