RB-02 * PHASE I/II CLINICAL TRIAL USING TRANS SODIUM CROCETINATE AS A RADIOSENSITIZER FOR GLIOBLASTOMA

Abstract

BACKGROUND: Trans sodium crocetinate (TSC) was developed at UVA to increase tissue oxygenation. Since hypoxic tumors are more resistant to radiation therapy (RT), TSC was demonstrated to increase survival in a rat GBM model. TSC has been used in an open GBM clinical trial in conjunction with TMZ and RT. All patients have undergone at least one year of treatment/check-ups. METHOD(S): 59 patients with newly diagnosed GBM were enrolled between January 2012 and March 2013. Patients received standard of care RT and TMZ. TSC was also administered 3/week, prior to the RT sessions. The trial began with a Phase I portion to establish the safety of dosing TSC in 3 half-dose patients. Then 6 more patients received TSC for the full 6 weeks of RT. Since there were no dose-limiting toxicities, 50 more Phase II patients were enrolled at the higher dosage of TSC. Four weeks after completion of RT, patients resumed TMZ for 5 days every 4 weeks, but no further TSC was administered. The patients continued to receive bi-monthly check-ups for MRI, KPS scores and Quality of Life questions. The principal efficacy measurement is survival at 24 months as compared to a historical control (Stupp 2005). RESULT(S): At a time of 12 months since the diagnosis of GBM: survival = 70% of the 56 full-dose patients are alive as compared to 61 % in the Stupp 2005 trial; radiologic response shows 6 full-dose patients who began RT with partially-resected tumors now show no tumor, while another 13 show declining tumors. 7 patients who began RT following complete resections still show no detectable tumor. Thus, 46% of the patients exhibit decreased or zero tumor volumes; SAFETY: The patients tolerated the concurrent dosing of TMZ and TSC during RT extremely well. Only one patient experienced TMZ-induced thrombocytopenia.