BPM31510 in Treating Patients With Recurrent High-Grade Glioma Previously Treated With Bevacizumab

Primary Objective:

- Assess the safety and tolerability of BPM31510 plus vitamin K in subjects with
high-grade glioma(HGG), defined as anaplastic astrocytoma (AA) or glioblastoma (GB) that
has recurred on a BEV containing regimen.

Secondary Objectives:

- To evaluate plasma pharmacokinetics (PK) when BPM31510 plus vitamin K is given to
subjects with HGG recurrent on a BEV containing regimen.

Exploratory Objectives:

- Estimate the overall survival in subjects with HGG recurrent on a BEV containing regimen
from the 1st day of infusion of BPM31510 plus vitamin K to death.

- To evaluate the effects of BPM31510 plus vitamin K on shifting HGG metabolism to aerobic
respiration by PET imaging.

- To evaluate the effects of BPM1510 plus vitamin K on MRI imaging by Response Assessment
in Neuro Oncology (RANO) criteria [specifically progression free survival (PFS) and
response rate (RR)].

- To evaluate plasma pharmacodynamics (PD) when BPM31510 plus vitamin K is given to
subjects with HGG recurrent on a BEV containing regimen.

Inclusion Criteria:

- Be ≥ 18 years of age

- Have a life expectancy ≥ 6 weeks

- Have a Karnofsky Performance Score (KPS) ≥ 60

- Have pathologically proven GB, gliosarcoma (WHO IV), or anaplastic astrocytoma (WHO
III) in recurrence after treatment with bevacizumab

- Be at least 14 days from the last administration of bevacizumab

- Be at least 28 days from last administration of cytotoxic chemotherapy or other
investigational agent

- Have received radiation therapy with concurrent temozolomide. Total radiation dosage
can range from 5400 to 6000 cGy administered in daily fractions of 150 to 200 cGy over
6 weeks, or the equivalent in a hypofractionated protocol (for example, 4000cGy in 15
fractions or 2500cGy in 5 fractions). Patients who are MGMT negative do not need to
have received temozolomide.

- Have adequate organ and marrow function as follows (all required):

- ANC ≥ 1500 mm3

- Platelets ≥ 100,000/mm3

- Hemoglobin ≥ 9 g/dL

- Serum creatinine ≤ 1.8 mg/dL or creatinine clearance > 50 mL/min Bilirubin ≤ 1.5
mg/dL

- Alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN)

- Aspartate transaminase (AST) ≤ 2.5 x ULN

- Prothrombin time (PT) ≤ 1.5 x ULN

- International Normalized Ratio (INR) ≤ 1.5 x ULN

- Partial thromboplastin time (PTT) ≤ 1.5 x ULN

- Subjects of childbearing potential must agree to use hormonal or barrier birth control
with spermicidal gel to avoid pregnancy during the study

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- Has a history of spontaneous or tumor related cerebral hemorrhage; or has cerebral
hemorrhage as determined by the screening FDG PET CT and MRI. This does not include
stable post operative blood products seen on a gradient echo MRI sequence.

- Has the any of the following cardiac history:

- Active heart disease including myocardial infarction within previous 3 months

- Symptomatic coronary artery disease

- Arrhythmias not controlled by medication

- Unstable angina pectoris

- Uncontrolled or symptomatic congestive heart failure (NYHA class III and IV)
3.2.3 Uncontrolled or severe coagulopathies or a history of clinically
significant bleeding within the past 6 months, including any of the following,
but not limited to:

- Epistaxis

- Hemoptysis

- Hematochezia

- Hematuria

- Gastrointestinal bleeding

- Spontaneous or tumor related intracranial hemorrhage

- Known predisposition for bleeding such as von Willebrand's disease or other such
condition(s)

- Uncontrolled concurrent illness that would limit compliance with study requirements,
including any of the following, but limited to:

- Uncontrolled infection.

- Psychiatric illness/social situations

- Prior malignancy except for non melanoma skin cancer and carcinoma in situ (of the
cervix or bladder), unless diagnosed and definitively treated more than 3 years prior
to 1st dose of investigational drug

- Receiving any of the following medications:

- Therapeutic doses of any anticoagulant, including low molecular weight heparin
(LMWH). Concomitant use of warfarin, even at prophylactic doses, is prohibited

- Digoxin, digitoxin, lanatoside C, or any type of digitalis alkaloids.

- Colony stimulating factors (CSFs) that cannot be held during the monitoring
period for dose limiting toxicities (DLT)

- Has significant toxicities from prior treatment that have not resolved or stabilized

- Known allergy to Coenzyme Q10

- Known allergy or adverse reaction to oral, subcutaneous, or intravenous vitamin K

- Is pregnant or lactating

- Known to be positive for the human immunodeficiency virus (HIV). Note: HIV testing is
not required for eligibility, but if performed previously and was positive, the
subject is ineligible.