Phase II study of CT-322, a targeted biologic inhibitor of VEGFR-2 based on a domain of human fibronectin, in recurrent glioblastoma (rGBM).

Abstract

2011 Background: VEGF signaling through VEGFR-2 is the major factor in glioblastoma angiogenesis. CT-322, a pegylated protein engineered from the tenth type III human fibronectin domain, binds the VEGFR-2 extracellular domain with high specificity and affinity to block VEGF-induced VEGFR-2 signaling. This study evaluates CT-322 in an open-label phase II setting to assess its efficacy and safety in rGBM. Methods: Eligibility: age ≥ 18; histologically confirmed rGBM in 1st to 3rd relapse; no prior anti-angiogenic therapy; measurable disease on contrast-enhanced MRI; KPS ≥ 70; ≥ 12 weeks from RT completion; no CNS hemorrhage; and no anticoagulants. This noncomparative trial assigned pts to IV weekly CT-322 at 1 mg/kg or 2 mg/kg and within each dose randomized pts to ± irinotecan (I) (125 mg/m2 q2w if no enzyme-inducing antiepileptics [EIAEDs]; 340 mg/m2 IV q2w if on EIAEDs). One cycle is 4 weeks. Primary end point is 6-mo progression-free survival (PFS-6). Planned enrollment is 75 pts. All results are ITT po...