Hepatocellular carcinoma recurrence after curative treatment adversely influences clinical outcome. It is important to explore adjuvant therapies . This phase II/stage 1 multi- center, randomized trial investigated the safety, optimal dosage and preliminary efficacy of PI-88, a novel heparanase inhibitor, in the setting of post-operative recurrence of HCC according to a Simon's 2-stage design. Methods: Three groups were included : one untreated arm (Group A) and two PI -88 arms (Group B: 160 mg/day; Group C: 250 mg/day). Treatment groups received PI-88 over nine 4-week treatment cycles, followed by a 12-week treatment-free period. Safety and optimal dosage were assessed. Results: Overall, 172 patients were randomized and 168 were included in the intention-to-treat (ITT) population. Treatment-related adverse effects included cytopenia, injection site hemorrhage, PT prolongation, etc. Four serious adverse events were possibly related to PI-88 treatment. One (1.8%) group B patients and six (10.5%) group C had hepatotoxicity- related withdrawals. Among the ITT population, 29 patients( 50%) in Group A, 35 (63%) in Group B, and 22 (41%) in Group C remained recurrence-free at completion. Calculated T-1 value suggested 160 mg/day treatment satisfied the criteria for the next stage of the trial. Conclusions: PI-88 at 160 mg/day is optimal and safe, and shows preliminary efficacy as an adjunct therapy for postoperative HCC. ; 臨床醫學研究所 ; 醫學院 ; 期刊論文