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

Invest New Drugs. 2008 Feb;26(1):89-94. doi: 10.1007/s10637-007-9080-5. Epub 2007 Sep 20.


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 >or=20%, there is some evidence of activity and further investigation is warranted.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Alanine Transaminase / blood
  • Contusions / etiology
  • Drug Administration Schedule
  • Fatigue / chemically induced
  • Female
  • Glucuronidase / antagonists & inhibitors*
  • Humans
  • Injections, Subcutaneous / adverse effects
  • Kaplan-Meier Estimate
  • Male
  • Melanoma / drug therapy*
  • Melanoma / pathology
  • Middle Aged
  • Nausea / chemically induced
  • Neoplasm Metastasis
  • Oligosaccharides / administration & dosage
  • Oligosaccharides / adverse effects
  • Oligosaccharides / therapeutic use*
  • Pain / etiology
  • Severity of Illness Index
  • Thrombocytopenia / chemically induced
  • Treatment Outcome


  • Oligosaccharides
  • phosphomannopentaose sulfate
  • Alanine Transaminase
  • heparanase
  • Glucuronidase