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.