clinical
trialscompleted clinical trials
TM601-001 - Phase 1/2 Single-Dose Study of 131I-TM601 in Patients with Recurrent Glioma (Intracavitary)
A total of 18 adult patients with recurrent high-grade glioma requiring tumor resection were treated on this study at 3 clinical sites. Six patients were treated at each of 3 dose levels, 0.25 mg, 0.50 mg, and 1.0 mg with the TM601 radio-labeled with 10mCi of 131I. The primary goals of this Phase 1/2 study were to determine the safety, tolerability, biodistribution and dosimetry of 131I-TM601 when administered via the intracavitary route as 131I-TM601. The study evaluated the safety and toxicity, biodistribution, dosimetry, clearance and metabolism. The secondary goal of the study was to determine the tumor response based on radiographic measurements to monitor tumor response, recurrence and time to progression. The safety and dosimetry data from this first-in-human Phase I study suggested that the doses of TM601 and radiation could be further escalated and although the sample size was small, there was a suggestion of efficacy with even a single dose in this population. Results of this study were published in the August 2006 Journal of Clinical Oncology. For more information on this article, click here.
TM601-002 - Phase 2 Multiple-Dose Study of 131I-TM601 in Patients with Recurrent Glioma (Intracavitary)
Based on the results of the Phase 1/2 study, a Phase 2 trial in recurrent glioma was initiated and designed to extend the previous results by treating patients with recurrent high grade glioma with multiple doses of 131I-TM601. The goals of this Phase 2 trial were to determine the maximum tolerated dose (MTD) of 131I-TM601 and to evaluate the toxicity of three and six doses of 131I-TM601. The secondary endpoints included 6 and 12 month progression free survival and overall survival. This Phase 2 study was conducted in two separate sequences: the first portion, a dose escalation stage, has been completed; the second portion, a stage in which patients were randomized to receive either 3 or 6 doses, has completed enrollment. No dose limiting toxicities were observed in the dose escalation portion of the trial in which 15 patients were treated. In the second sequence of the trial, 54 patients were randomized to receive either 3 or 6 injections of 131I-TM601 at 0.8 mg of peptide / 40 mCi 131I. The safety and efficacy parameters of the two dosing regimens are being evaluated. To date, there is an early acceptable toxicity profile with the type and severity of adverse events (AEs) not unexpected, and interim analysis of survival data has been encouraging with median survival exceeding historical controls.
TM601-004 - A Dosimetry Study of 131I-TM601 in Recurrent Glioma (Intracavitary)
This study is a dosimetry sub-study of patients enrolled in the TM601-002 treatment protocol and evaluated the biodistribution (% injection dose) and clearance of 131I of multiple intracavitary doses of 131I-TM601. The study evaluated the organ dosimetry of up to five patients receiving treatment on Protocol TM601-002 (see above description). Reproducibility of the biodistribution (% injection dose) and clearance of 131I in the resected tumor cavity and normal organs with significant uptake of 131I-TM601 was evaluated following the first, third and sixth 131I-TM601 injections. All subjects have been treated in this study and analysis is ongoing.
TM601-003 - Phase 1 Multiple-Dose Study of 131I-TM601 in Patients with Metastatic Solid Tumors (Intravenous)
131I-TM601 has also been studied in a Phase 1 imaging and safety study of intravenous 131I-TM601 in patients with recurrent or refractory somatic and/or cerebral metastatic solid tumors (TM601-003). Pre-clinical animal data has shown tumor-specific localization of 131I-TM601 following IV injection, and additional data demonstrate that 131I-TM601 has the ability to cross the blood brain barrier and bind to multiple tumor types. The objectives of this Phase 1 study were to evaluate whether intravenous 131I-TM601 provides tumor-specific localization in patients with recurrent or refractory metastatic (including brain metastases) solid tumors, to determine the distribution and dosimetry of intravenously administered 131I-TM601, and to determine the safety and tolerability of intravenously administered 131I-TM601. Safety data reported as of May 31, 2008 indicate that repeat doses of 131I-TM601 have been shown to be well tolerated when delivered intravenously to the patient populations studied. Additionally, tumor specific uptake of 131I-TM601 after intravenous dosing was shown in 10 distinct cancer indications including: malignant glioma, malignant melanoma (including patients with brain metastases), colon cancer, non small cell lung cancer, prostate cancer, pancreatic cancer, breast cancer, transitional cell carcinoma, metastatic paraganglioma, and pleomorphic xanthoastrocytoma. This trial has now completed enrollment.