A phase II study of the heparanase inhibitor PI-88 in patients with advanced melanoma

Karl D. Lewis, William A. Robinson, Michael J. Millward, Alex Powell, Timothy J. Price, Damien B. Thomson, Euan T. Walpole, Andrew M. Haydon, Brian R. Creese, Kaye L. Roberts, John R. Zalcberg, Rene Gonzalez

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Treatment options for advanced melanoma are limited. PI-88, a potent inhibitor of heparanase, demonstrates anitangiogenic properties and has shown activity against melanoma in phase I studies. This was an open-label, multicenter, phase II study of PI-88 in patients with advanced melanoma. Patients received a fixed-dose of 250 mg/day given subcutaneously for four consecutive days followed by three drug-free days per week in a 28-day cycle. A total of 44 patients were enrolled in the intent to treat population, with 59.1% having received previous therapy. The median time to progression and overall survival was 1.7 months and 9 months, respectively. Forty-one patients are included in the efficacy analysis. One (2.4%) patient achieved a partial response, six (14.6%) patients had stable disease as best response, and 30 (73.2%) had progressive disease. At the end of six cycles of treatment, three of the 41 evaluable patients had non-progressive disease. Treatment was generally well tolerated. Injection site bruising occurred in 45% of patients. Serious bleeding did occur in two patients and three patients developed a positive anti-platelet antibody test during the study. One of these four patients experienced an associated thrombosis. In patients with advanced melanoma, PI-88 demonstrates an overall survival and time to progression similar to standard chemotherapy. Although the current study did not meet the primary end-point of progression free survival of >/=20%, there is some evidence of activity and further investigation is warranted.

Original languageEnglish
Pages (from-to)89-94
Number of pages6
JournalInvestigational New Drugs
Issue number1
Publication statusPublished - 1 Feb 2008


  • Heparanase inhibitor
  • Melanoma
  • PI-88

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