A phase I/II clinical trial for adult recurrent glioma using 131i-tm-601, an iodinated peptide derived from scorpion venom

131I-TM-601 is a 36-amino acid peptide, called chlorotoxin (TM-601), derived from scorpion venom labeled with I-131. TM-601 binds a receptor on the surface of tumor cells, and not on normal cells. A single dose of 131I-TM-601 administered intracranially to human xenografted mouse models of glioma has been shown to extend survival up to 269% in multiple studies. 131I-TM-601 is in a multi-center phase I/II clinical trial for adult recurrent glioma. A total of 18 patients, six in each of three dosing panels (10 mCi/250 g 10 mCi/500 g, and 10 mCi/1000 g) were studied. Patients have a ventricular access device (VAD) placed in the tumor cavity at the time of resection. 14 to 28 days later, a single dose (2 ml) of 131I-TM-601is given via the VAD. Gamma, SPECT, and MRI/CT scans are taken over a six to eight day period. The primary endpoints are safety, toxicity, dosimetry, biodistribution and imaging and the secondary endpoints are tumor response and survival. Enrollment is complete. No dose limiting toxicities directly related to drug administration has been observed. Specific targeting of residual tumor in the cavity has been demonstrated. One to 10% of the radiation delivered specifically binds the tumor cavity. Biodistribution and dosimetry data indicate that targeting of 131I-TM-601 to the tumor cavity is very high and to critical organs very low. By 72 hours, 90% of the radiation has been eliminated from the body. Patients were followed for six months or until death. Studies were approved by Institutional Review Board under an IND from FDA. A single dose of 131I-TM-601appears to be safe, well tolerated, and to target tumor cells with high specificity. A phase II clinical trial using multiple doses of 131I-TM-601 with higher dose of radiation is planned.