Heparanase inhibitor PI-88 as adjuvant therapy for hepatocellular carcinoma after curative resection: a randomized phase II trial for safety and optimal dosage - PubMed (original) (raw)

Clinical Trial

doi: 10.1016/j.jhep.2008.12.023. Epub 2009 Feb 15.

Po-Huang Lee, Deng-Yn Lin, Cheng-Chung Wu, Long-Bin Jeng, Pin-Wen Lin, King-Tong Mok, Wei-Chen Lee, Hong-Zen Yeh, Ming-Chih Ho, Sheng-Shun Yang, Ching-Chih Lee, Ming-Chin Yu, Rey-Heng Hu, Cheng-Yuan Peng, Kuan-Lang Lai, Stanley Shi-Chung Chang, Pei-Jer Chen

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Clinical Trial

Heparanase inhibitor PI-88 as adjuvant therapy for hepatocellular carcinoma after curative resection: a randomized phase II trial for safety and optimal dosage

Chun-Jen Liu et al. J Hepatol. 2009 May.

Abstract

Background/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 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 post-operative HCC.

Trial registration: ClinicalTrials.gov NCT00247728.

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