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

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 chemo¬radiation 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 comple¬tion 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 pre¬clinical 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.

Inclusion Criteria:

- Subjects must have histologically confirmed diagnosis of World Health Organization
(WHO) grade III or IV malignant glioma

- Subjects must be planning to start standard of care radiation therapy and chemotherapy

- Subjects must be within 12 weeks of last major neurosurgical procedure for the
high-grade glioma (craniotomy, open biopsy, or stereotactic biopsy)

- Subjects must have had a definitive resection with residual radiographic contrast
enhancement on post-resection CT or MRI of less than or equal to 2 cm in any two
perpendicular planes on any images

- Age * 18 years

- Karnofsky Performance Status (KPS) ≥ 70%

- Hemoglobin ≥ 9.0 g/dl, absolute neutrophil count (ANC) ≥ 1,500 cells/µl, platelets ≥
125,000 cells/µl

- Serum creatinine ≤ 1.5 mg/dl, serum glutamate oxaloacetate transaminase (SGOT) and
bilirubin ≤ 1.5 times upper limit of normal

- Signed informed consent approved by the Institutional Review Board

- If sexually active, patients must agree to use appropriate contraceptive measures for
the duration of the study and for 12 months afterwards as stated in the informed
consent

- Stable and/or decreasing dose of corticosteroids for greater than or equal to 7 days.

Exclusion Criteria:

- Pregnancy or breast-feeding

- Active infection requiring IV antibiotics 7 days before enrollment

- Signs of wound-healing problems or infection at the craniotomy/biopsy site.

- Prior, unrelated malignancy requiring current active treatment with the exception of
cervical carcinoma in situ and adequately treated basal cell or squamous cell
carcinoma of the skin

- Co-medication that may interfere with study results; e.g. immuno-suppressive agents
other than corticosteroids

- Prior treatment with radiotherapy or chemotherapy for a brain tumor, irrespective of
the grade of the tumor

- Evidence of > grade 1 CNS hemorrhage on baseline MRI on CT scan

- Systemic treatment with inducers or strong inhibitors of cytochrome P450 within four
days before enrollment or planned treatment during the time period of the study.

- Metal in the body (except dental fillings) e.g., pacemaker, infusion pump, metal
aneurysm clip, metal prosthesis, joint, rod or plate.

- Severe allergy to contrast agent.