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

Phase 1
18 Years
Open (Enrolling)
Brain Cancer

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Trial Information

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

Protection from apoptosis is a key survival factor for cancer cells. Dexanabinol is under
investigation as a novel anti-cancer therapy based on its tumoricidal activity observed in
vitro and in vivo, presumably due to inhibitory activity against NFĸB, TNFα, COX-2 and
additional putative targets suck as HAT, FAT and cyclin dependent kinases. Targeted
induction of apoptosis in cancer cells versus normal cells provides an attractive strategy
for the treatment of brain cancer, a pernicious disease with debilitating neurological side
effects and poor prognoses. A single intravenous dosing of dexanabinol has demonstrated
safety in humans. Therefore, we are conducting a phase I dose escalation study to examine
the safety of multiple dosing of dexanabinol and drug penetration into the brain, and to
determine a suitable dose for moving into a phase II trial for efficacy.

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

- 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.

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

- 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.

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Rate of dose limiting toxicities and the maximum tolerated dose (MTD) of weekly dexanabinol

Outcome Time Frame:

first 28 days of treatment

Safety Issue:


Principal Investigator

Santosh Kesari, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of California Medical Center


United States: Food and Drug Administration

Study ID:




Start Date:

June 2012

Completion Date:

December 2013

Related Keywords:

  • Brain Cancer
  • Brain
  • Glioma
  • glioblastoma
  • metastases
  • cancer
  • ETS2101
  • leptomeningeal
  • astrocytoma
  • oligodendroglioma
  • meningioma
  • Brain Neoplasms



Moores UCSD Cancer Center La Jolla, California  92093-0658