CHUN-JEN LIUPO-HUANG LEELin D.-Y.Wu C.-C.Jeng L.-B.Lin P.-W.Mok K.-T.Lee W.-C.Yeh H.-Z.MING-CHIH HOYang S.-S.Lee C.-C.Yu M.-C.REY-HENG HUPeng C.-Y.Lai K.-L.Chang S.S.-C.PEI-JER CHEN2020-02-192020-02-1920090168-8278https://www.scopus.com/inward/record.uri?eid=2-s2.0-84984569951&doi=10.1016%2fj.jhep.2008.12.023&partnerID=40&md5=216d251a9678ba022249dadcf8cbdd4bhttps://scholars.lib.ntu.edu.tw/handle/123456789/461667Background/Aims: 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 T1 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 post-operative HCC. ? 2009 European Association for the Study of the Liver.[SDGs]SDG3pi 88; placebo; acute pancreatitis; adjuvant therapy; adult; adverse outcome; alanine aminotransferase blood level; alopecia; article; aspartate aminotransferase blood level; brain hemorrhage; cancer recurrence; cancer staging; cancer surgery; clinical trial; controlled clinical trial; controlled study; cytopenia; drug dose comparison; drug efficacy; drug safety; drug tolerability; drug withdrawal; female; gingiva bleeding; human; human cell; human tissue; injection site bleeding; liver cell carcinoma; liver rupture; liver toxicity; major clinical study; male; metastasis; multicenter study; multiple cycle treatment; muscle spasm; neutropenia; outcome assessment; patient satisfaction; phase 2 clinical trial; postoperative complication; priority journal; pt prolongation; QT prolongation; randomized controlled trial; side effect; thrombocytopenia; treatment durationjournal article10.1016/j.jhep.2008.12.023193031602-s2.0-84984569951