title: A phase II study of ABT-510 (thrombospondin-1 analog) for the treatment of metastatic melanoma.
abstract: OBJECTIVE
  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).
  
  
  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.
authors.affiliation: Department of Oncology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. markovic.svetomir@mayo.edu
authors.forename: Svetomir N
authors.initials: SN
authors.lastname: Markovic
authors.forename: Vera J
authors.initials: VJ
authors.lastname: Suman
authors.forename: Ravi A
authors.initials: RA
authors.lastname: Rao
authors.forename: James N
authors.initials: JN
authors.lastname: Ingle
authors.forename: Judith S
authors.initials: JS
authors.lastname: Kaur
authors.forename: Lori A
authors.initials: LA
authors.lastname: Erickson
authors.forename: Henry C
authors.initials: HC
authors.lastname: Pitot
authors.forename: Gary A
authors.initials: GA
authors.lastname: Croghan
authors.forename: Robert R
authors.initials: RR
authors.lastname: McWilliams
authors.forename: Jaime
authors.initials: J
authors.lastname: Merchan
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Kottschade
authors.forename: Wendy K
authors.initials: WK
authors.lastname: Nevala
authors.forename: Cindy B
authors.initials: CB
authors.lastname: Uhl
authors.forename: Jacob
authors.initials: J
authors.lastname: Allred
authors.forename: Edward T
authors.initials: ET
authors.lastname: Creagan
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy*; D008875:Middle Aged; D009842:Oligopeptides / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000188:drug therapy*; D019700:Thrombospondin 1; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; C500617:NAc-Sar-Gly-Val-(d-allo-Ile)-Thr-Nva-Ile-Arg-ProNEt; D009842:Oligopeptides; D019700:Thrombospondin 1