Randomized Phase III Study Of Gemcitabine (GEM) vs Pegylated Liposomal Doxorubicin (PLD) in progressive/recurrent ovarian cancer

Secondary Objective(s): Randomized Phase III Study Of Gemcitabine (GEM) vs Pegylated Liposomal Doxorubicin (PLD) in progressive/recurrent ovarian cancer Primary Objective: Compare TTP in progressive/recurrent ovarian cancer patients failing platinum/paclitaxel-based chemotherapy Secondary Objective(s): Overall Survival (OS) Response Rate (RR) Duration of response Safety/toxicity QoL Sample size: a total of 147 pts is needed (Alpha=0.05, Beta=0.8), in order to detect a difference in the hazard ratio of 58% (median TTP 12 to 19 weeks)

Inclusion Criteria Recurrent OC failing platinum/paclitaxel CT and measurable or evaluable lesions No more than one prior CT with a platinum+taxane regimen and treatment-free interval <12 months Age >18 ECOG Performance status < 2 , life expectancy >12 weeks Normal haematological, renal, hepatic, cardiac, respiratory function LVEF >50% Written informed consent

Exclusion Criteria Previous or current malignancies at other sites Brenner’s and borderline ovarian tumors Hb<9gr/dL; ANC<1500/uL; PLT<100000/uL; Creat.>1.5mg/dL or Creat. clear.<50 cc/min; Bil. >1.5mg/dL; AST,ALT>1.5 normal Other investigational cytotoxic drug within 4 weeks before Uncontrolled severe, viral, fungal or parasitic infection Symptomatic CNS metastases Severe medical problems unrelated to malignancy limiting compliance with the study or exposing the patient to extreme risk

Study Design GEMCITABINE: 1000 mg/m2 d1,8,15 q28 PLD: 40 mg/m2 d1 q28 (until progression of disease or unacceptable toxicity) Evaluation of response: every two cycles (RECIST)

Patient Characteristics at Diagnosis GEM PLD Enrolled 77 76 FIGO stage I-II III IV 3 51 23 4 49 23 Grading 1-2 3 n.a. 15 48 14 12 50 14 Histotype Serous Undifferentiated Clear cell Endometrioid Mucinous Mixed 59 4 6 5 1 2 64 2 4 3 1 Mito 3

Patient Characteristics at Recurrence GEM PLD Recruited 77 76 Age yrs (median,range) 63 (39 - 79) 63 (28 - 80) PFI < 6 months 43 (55.8%) 43 (56.6%) 7 - 12 months 34 (44.2%) 33 (43.4%) PS (ECOG) 0/1/2 38/33/6 33/39/4 Recurrence (site) Abdominal Lymph node Pelvis Mixed 25 8 36 24 6 12 34 CA125 (IU/ml (range)) 243 (3-9.870) 165 (4-3.280) Mito 3

Study Drug Administration Details GEM PLD Total Cycles administered 269 290 Median No. Cycles/patient (range) 3.0 (1 - 12) 3.5 (1 - 14) Median cumulative dose/patient (mg/mq) (range) 9,000 (1,000 - 31,000) 120 (35 - 600) No Cycles with delay 13 (4.5%) 32 (11.8%) No Cycles with reduction 24 (8.3%) 22 (8.2%) Mito 3