A phase II study of ABT-510 (thrombospondin-1 analog) for the treatment of metastatic melanoma

Svetomir Nenad Markovic, Vera Jean Suman, Ravi A. Rao, James N. Ingle, Judith S Kaur, Lori A. Erickson, Henry Clement Pitot, Gary A. Croghan, Robert R Mc Williams, Jaime Merchan, Lisa A. Kottschade, Wendy K. Nevala, Cindy B. Uhl, Jacob Allred, Edward T. Creagan

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Abstract

OBJECTIVES: Thrombospondins are natural inhibitors of angiogenesis, tumor metastases, and tumor growth (melanoma). ABT-510 is a synthetic analog of thrombospondin-1, well tolerated in phase I studies. We conducted a phase II trial evaluating the clinical efficacy of ABT-510 and its effects on biomarkers of angiogenesis and immunity in patients with metastatic melanoma (MM). PATIENTS AND METHODS: A 2-stage phase II clinical trial was conducted to assess the clinical efficacy, safety, and pharmacodynamic effects (angiogenesis and immunity) of ABT-510 in patients with stage IV melanoma. The primary endpoint was 18-week treatment failure rate. Patients self-administered 100 mg of ABT-510 subcutaneously twice daily. Blood samples were collected at baseline and every 3 weeks while on therapy. Eligible patients demonstrated measurable disease, good performance status and no evidence of intracranial metastases. Correlative laboratory studies evaluated biomarkers of angiogenesis and immunity. RESULTS: Twenty-one patients were enrolled. Most patients were stage M1c (71%) and all had prior therapy for MM. Only 3 of the first 20 patients enrolled were progression free and on treatment at 18 weeks resulting in early termination of the study. Decreases in peripheral blood VEGF-A levels and VEGF-C levels, and CD146 and CD34/133 counts relative to pretreatment were detected. Limited changes in antitumor T cell immunity were observed. CONCLUSIONS: ABT-510 therapy administered at 100 mg twice/day in patients with MM did not demonstrate definite clinical efficacy. Further dose escalation or combination with cytotoxic therapy may be more effective therapeutically.

Original languageEnglish (US)
Pages (from-to)303-309
Number of pages7
JournalAmerican Journal of Clinical Oncology: Cancer Clinical Trials
Volume30
Issue number3
DOIs
StatePublished - Jun 2007

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Keywords

  • ABT-510
  • Antiangiogenesis
  • Immune homeostasis
  • Melanoma
  • Thrombospondin-1

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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