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.