A Phase I, Sequential Cohort, Open-Label, Dose-escalation Study of the Safety and CNS Pharmacokinetics of Dexanabinol in Patients With Brain Cancer
- 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
- 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
- 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
- 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
- Alkaline phosphatase (ALP) ≤ 2.5 x ULN unless considered tumor related
- Estimated GFR > 50 ml/min (based on Wright formula)
- 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
- Woman of child-bearing potential has negative pregnancy test before the
initiation of study drug dosing.
- 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
- 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
- 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
- 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.