completed glioma clinical trials

clinical trials overview | completed glioma clinical trials | active studies

TM601-001 – Phase I/II single-dose dose open label study in patients with recurrent glioma:
A phase I/II open label, single-dose study of intracavitarily administered I-TM601 in adult patients with recurrent high-grade glioma was completed. Single doses ranging from 0.25 mg TM601 plus 10 mCi I to 1.00 mg TM601 plus 10 mCi I were administered to 18 patients through an intracavitary route following surgical tumor de-bulking. Patients had recurrent glioma after receiving standard therapy.

Results showed that I-TM601 was well tolerated up to the maximum dose of 1.00 mg TM601 plus 10 mCiI. No Grade 3 toxicities assessed as “probably related” to treatment were observed, therefore the dose of 131I TM601 was escalated up to the protocol’s maximum dose of 1.00 mg TM 601/10mCi I. No adverse events (AEs) occurred which required interruption of I TM601 infusion.

Efficacy was not the primary end point of the trial. However, imaging and survival evaluations revealed the following:

•	Two patients who had received 0.50 TM601 plus 10 mCi I had >50% reductions in tumor size following treatment.
•	Eighteen (of 18) patients were still alive at 4 months follow-up.
•	Eight patients were still alive at 6 months follow-up.
•	Five patients survived beyond 12 months.
•	Two patients achieved long-term (> 3 years) survival.

Dosimetry studies were also conducted as part of the phase 1/2 study. Results demonstrated that, while high radiation doses were delivered via TM601 to the tumor cavity, minimal radiation reached other body tissues, indicating that dosages can be substantially increased without harming normal tissue.

TM601-002 – Phase 2 open-label, multiple-dose study of intracavitarily delivered 131I-TM601 in patients with high-grade glioma

The first stage of this study was an open-label, dose escalation, multi-dose study. Four cohorts were treated postoperatively at escalating dose levels until the Maximum Practical Dose (MPD) was reached or until determination of the Maximum Tolerated Dose (MTD). The first stage of this study was completed with good safety and tolerability and no Dose Limiting Toxicity (DLT) was observed.

The second stage was an open-label, randomized study in 54 patients randomized to either a 3- or 6-dose treatment cycles of intracavitarily administered I-TM601. This stage of the study evaluated both safety and efficacy parameters of the two dosing regimens. Efficacy parameters include overall time to disease progression at 6 and 12 months, and survival rates after treatment. This study has completed the treatment phase in all patients.

Interim results have demonstrated an improvement of median survival in this difficult to treat patient population, prompting positive discussions with the FDA regarding pivotal Phase 3 trial design and early approval. The Company is working with the FDA to reach agreement through the Special Protocol Assessment (SPA) process regarding the design of a Phase 3 trial in newly diagnosed glioma in combination with temozolomide and radiotherapy, the current standard of care.

TM601-004 - A Dosimetry Study of 131I-TM601 In Malignant Glioma (Intracavitary)

The study was a dosimetry sub-study of patients enrolled in the TM601-002 treatment protocol and is intended to evaluate the biodistribution (% injection dose) and clearance of I of multiple intracavitary doses of I-TM601. The study will evaluate 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 I in the resected tumor cavity and normal organs with significant uptake of I-TM601 will be evaluated following the first, third and sixth I-TM601 injections. All subjects have been treated in this study and analysis is ongoing.