A phase I evaluation of intravenous TM601 in recurrent glioblastoma: Use of perfusion MRI to monitor antiangiogenic effects.

Academic Article

Abstract

  • 2041 Background: TM601, a synthetic chlorotoxin, is a peptide derived from scorpion venom. In vitro data demonstrate binding to vascular endothelial cells, and blockage of endothelial cell invasion. In vivo, intravenous infusion of TM601 decreases neovascularization. Based on this work and previous clinical trials demonstrating tumor-specific uptake of (131)I-TM601 in malignant glioma after IV delivery, a phase I trial was initiated with intravenous unlabeled TM-601. METHODS: Six patients with recurrent glioblastoma have been enrolled. All patients received a test dose of 10 mCi (131)I-TM601 to demonstrate tumor-specific uptake prior to TM601 treatment at doses of 0.04 mg/kg IV weekly for 3 weeks in a 4 week cycle. Treatment continued until tumor progression. Patients were evaluated at week 4 of each cycle with conventional and dynamic susceptibility contrast MRI (DSC-MRI) to assess perfusion. Anatomic and perfusion MRI evaluations were performed at baseline, 1 day after the initiation of TM601 therapy, and 21 days after initiation of each treatment cycle. MRI data were post-processed to yield an arterial input function and parametric hemodynamic maps. RESULTS: With respect to safety, there has been one intratumoral hemorrhage that was considered to be possibly related to therapy. Three other serious adverse events considered to be unrelated to therapy included disease progression on therapy, a hip fracture and renal calculi in a patient with a history of renal calculi. Two of six patients in the first dosing cohort have demonstrated a greater than 25% reduction in relative cerebral blood flow (rCBF) and/or relative cerebral blood volume (rCBV) compared to baseline. Both patients with improvement in perfusion MRI had extended response to intravenous TM601. CONCLUSIONS: Intravenous unlabeled TM601 at the initial dose schedule produces measurable changes in perfusion MRI parameters which correlate with clinical response. Perfusion MRI parameters appear to correlate with clinical response to TM601 and are consistent with angiogenic inhibition. [Table: see text].
  • Published In

    Pubmed Id

  • 11829689
  • Author List

  • Akella NS; Nabors LB; Rosenfeld SS; Chamberlain MC; Mrugala MM; Jacoby DB; O'Neill AM
  • Start Page

  • 2041
  • Volume

  • 27
  • Issue

  • 15_suppl