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Investigational New Drugs

, Volume 26, Issue 1, pp 89–94 | Cite as

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

  • Karl D. LewisEmail author
  • 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 GonzalezEmail author
Phase II Studies

Summary

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.

Keywords

Melanoma PI-88 Heparanase inhibitor 

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Karl D. Lewis
    • 1
    Email author
  • William A. Robinson
    • 2
  • Michael J. Millward
    • 3
  • Alex Powell
    • 3
  • Timothy J. Price
    • 4
  • Damien B. Thomson
    • 5
  • Euan T. Walpole
    • 5
  • Andrew M. Haydon
    • 6
  • Brian R. Creese
    • 7
  • Kaye L. Roberts
    • 7
  • John R. Zalcberg
    • 8
  • Rene Gonzalez
    • 2
    Email author
  1. 1.Cutaneous Oncology ProgramUniversity of Colorado Health Sciences CenterAuroraUSA
  2. 2.Cutaneous Oncology ProgramUniversity of Colorado Health Sciences CenterAuroraUSA
  3. 3.School of Medicine and PharmacologySir Charles Gairdner HospitalNedlands (Perth)Australia
  4. 4.Department of Haematology/OncologyThe Queen Elizabeth HospitalWoodville (Adelaide)Australia
  5. 5.Departments of Clinical Haematology and Medical Oncology, Division of Cancer ServicesPrincess Alexandra HospitalWoolloongabba (Brisbane)Australia
  6. 6.Medical Oncology UnitThe Alfred HospitalPrahran (Melbourne)Australia
  7. 7.Progen PharmaceuticalsToowong (Brisbane)Australia
  8. 8.Division of Haematology and Medical OncologyPeter MacCallum Cancer CentreMelbourneAustralia

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