A Phase I, Sequential Cohort, Open-Label, Dose-escalation Study of the Safety and CNS Pharmacokinetics of Dexanabinol in Patients With Brain Cancer

Inclusion Criteria:

- Histologically or radiologically confirmed diagnosis of brain cancer:

- glioblastoma (GBM),

- anaplastic astrocytoma (AA),

- anaplastic oligodendroglioma (AO),

- anaplastic mixed oligoastrocytoma (AMO),

- low grade gliomas,

- brain metastases,

- meningiomas, or

- leptomeningeal metastases

- Has failed prior standard therapy including maximal safe surgical resection,
radiation therapy (when appropriate for the specific cancer type), and systemic
therapy.

- For diagnosis of GBM: has undergone at least one prior surgical gross-total or
subtotal tumor resection, a course of postoperative radiation therapy with concurrent
temozolomide, and at least 2 cycles of maintenance temozolomide.

- For diagnosis of meningioma: has no other option of standard therapy such as surgical
resection (partial or total resection) or radiation.

- Has progression of brain cancer and measurable disease by magnetic resonance imaging
(MRI) or computed tomography (CT) scan.

- Age ≥ 18 years.

- Karnofsky Performance Status ≥ 60%. (Appendix A). Subjects must have a life
expectancy of equal to or greater than 8 weeks.

- Organ and Marrow Function Requirements

Hematology:

- Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L

- Platelet count ≥ 100 x 109/L

- Hemoglobin ≥ 9.0 g/dL

- White blood cell (WBC) count ≥ 3.0 x 109/L

Biochemistry:

- AST/SGOT and ALT/SGPT ≤ 2.5 x institution's ULN

- Total bilirubin ≤ 1.5 x institution's ULN

- Serum creatinine ≤ 1.5 x institution's ULN or 24-hour creatinine clearance ≥ 50
ml/min

- Alkaline phosphatase (ALP) ≤ 2.5 x ULN unless considered tumor related

- Estimated GFR > 50 ml/min (based on Wright formula)

Coagulation:

- INR < 1.5 x institution's ULN

- PT/aPTT within institution's normal range, unless receiving therapeutic low
molecular weight heparin

- Contraception Woman of child-bearing potential and man with partners of
child-bearing potential agrees to use adequate contraception (hormonal or
barrier method of birth control; abstinence) prior to study entry, for the
duration of study participation, and for 30 days following completion of
therapy.

- Woman of child-bearing potential has negative pregnancy test before the
initiation of study drug dosing.

Exclusion Criteria:

- Current or anticipated use of other investigational agents.

- Current or anticipated use of enzyme-inducing anti-epileptic drugs (EIAED).

- Insufficient time for recovery from prior therapy:

- less than 28 days from any investigational agent,

- less than 28 days from prior cytotoxic therapy (except 23 days from prior
temozolomide, 14 days from vincristine, 42 days from nitrosoureas, 21 days from
procarbazine administration), and

- less than 7 days for non-cytotoxic agents, e.g., interferon, tamoxifen,
thalidomide, cis-retinoic acid, etc. (radiosensitizer does not count).

- Less than 4 weeks from surgery or insufficient recovery from surgical-related trauma
or wound healing.

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to dexanabinol.

- History of allergic reactions to medicines containing polyoxyethylated castor oil
that are not controlled with premedications.

- Severe or uncontrolled medical disorder that would, in the investigator's opinion,
impair ability to receive study treatment (i.e., uncontrolled diabetes, chronic renal
disease, chronic pulmonary disease or active, uncontrolled infection).

- Electrolyte abnormality that cannot be corrected to normal levels prior to initiating
study drug.

- Known diagnosis of human immunodeficiency virus (HIV) infection.

- Impaired cardiac function including any of the following:

- Congenital long QT syndrome or a known family history of long QT syndrome;

- History or presence of clinically significant ventricular or atrial
tachyarrhythmias

- Clinically significant resting bradycardia (< 50 beats per minute)

- Inability to monitor the QT interval by ECG

- QTc > 450 msec on baseline ECG. If QTc > 450 and electrolytes are not within
normal ranges, electrolytes should be corrected and then the patient re-screened
for QTc

- Myocardial infarction within 1 year of starting study drug

- Other clinically significant heart disease (e.g., unstable angina, congestive
heart failure, or uncontrolled hypertension)

- Pregnant or nursing. There is a potential for congenital abnormalities and for this
regimen to harm nursing infants.