Last updated on October 2018

Trial of Newly Diagnosed High Grade Glioma Treated With Concurrent Radiation Therapy Temozolomide and BMX-001


Brief description of study

This is a Phase 2 study of newly diagnosed patients with high grade glioma (HGG) undergoing standard radiation therapy and temozolomide treatment. BMX-001 added to radiation therapy and temozolomide has the potential not only to benefit the survival of high grade glioma patients but also to protect against deterioration of cognition and impairment of quality of life. BMX-001 will be given subcutaneously first with a loading dose zero to four days prior to the start of chemoradiation and followed by twice a week doses at one-half of the loading dose for the duration of radiation therapy plus two weeks. Both safety and efficacy of BMX-001 will be evaluated. Impact on cognition will also be assessed. Eighty patients will be randomized to the treatment arm that will receive BMX-001 while undergoing chemoradiation and 80 patients randomized to receive chemoradiation alone. The investigators hypothesize that BMX-001 when added to standard radiation therapy and temozolomide will be safe at pharmacologically relevant doses in patients with newly diagnosed high grade glioma. The investigators also hypothesize that the addition of BMX-001 will positively impact the overall survival and improve objective measures of cognition in newly diagnosed high grade glioma patients.

Detailed Study Description

160 patients will be enrolled and randomized with a treatment arm allocation ratio of 1:1 in this Phase 2 study. At enrollment, patients will be assessed with patient history, physical/neurological examinations, standard laboratory evaluations (CBC with differential and comprehensive metabolic panel (CMP)), baseline MRI brain with and without gadolinium, cognitive testing and patient-reported outcome questionnaires of HRQoL. On the first day of BMX-001 (loading dose), patients will be evaluated with patient history, patient physical/neurological examinations, and standard laboratory evaluations (CBC with differential and CMP). Patients in Arm A will be administered BMX-001 subcutaneously first as a loading dose on the day before the start of chemoradiation and then at maintenance dose (50% of the loading dose) twice a week for 8 weeks. Because oxidative stress continues to occur for up to several weeks following RT, the proposed protocol includes administering BMX-001 both before the start of RT and continuing for 2 weeks after the completion of RT and TMZ. TMZ will be dosed at 75 mg/m2 orally daily for 42 days and RT will be delivered in daily fractions of 1.8-2 Gy given 5 days a week for 6 weeks for a total of 59.4-60 Gy. During standard RT and TMZ, CBC with differential will be obtained weekly and CMP will be obtained every 4 weeks. Two weeks after the completion of standard RT and TMZ and every 8 weeks during adjuvant TMZ, patients will be evaluated with the following: patient history, physical/neurological examinations, Brain MRI with and without gadolinium, cognitive testing and patient-reported outcome questionnaires of HRQoL. Two weeks after the completion of chemoradiation, patients will transition to adjuvant chemotherapy with TMZ dosed at 150-200 mg/m2 orally for 5 days of a 28-day cycle for a total of 12 cycles. In light of the findings that BMX-001 can spare radiation-induced hair loss in a mouse model [41], we will evaluate and describe hair loss as an exploratory outcome in HGG patients by evaluating hair at baseline and then every 8 weeks. Another exploratory endpoint, based on preclinical findings that BMX-001 protects white matter from radiation-induced damage [20], will be white matter integrity assessed using MRI diffusion tensor imaging. This will be obtained after enrollment, 2 weeks after the completion of standard RT and TMZ, and 24 weeks after the start of standard RT and TMZ. Patients will be discontinued from the study if they experience progression of disease, death or withdraw informed consent.

Clinical Study Identifier: NCT02655601

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Sarah Woodring

Duke Cancer Institute
Durham, NC United States
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