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

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

Research output: Contribution to journalArticlepeer-review

70 Scopus citations

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 1 2007
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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