Phase I Study of Mebendazole in Newly Diagnosed High-Grade Glioma Patients Receiving Temozolomide
Glioblastoma (GBM) is the most common and aggressive brain cancer, and despite significant
advances in treatment the majority of patients die within two years of diagnosis. During
routine animal studies we serendipitously observed that fenbendazole, a benzimidazole
antihelminthic used for pinworms, prevented tumor engraftment. Subsequent in vitro and in
vivo experiments with benzimidazoles identified mebendazole as the drug having the best
results in preclinical testing 1. In GBM cell lines, mebendazole displayed cytotoxicity
with IC50s ranging from 0.1-0.3 μM. Mebendazole disrupted microtubule formation in GBM
cells and it's in vitro activity was correlated with reduced tubulin polymerization. In two
orthotopic mouse glioma models, one syngeneic and one xenograft, mebendazole significantly
extended average survival up to 63% compared to untreated controls 1.
Mebendazole is an FDA approved antiparasitic agent with a well-established side effect and
safety record and was effective in our animal models in dosing schedules that are documented
as safe in humans. Therefore, mebendazole is a possible anti-cancer therapeutic with
pre-clinical safety and efficacy and provides a promising opportunity for a clinical trial
in patients with malignant gliomas.
In addition, a recently published case report case report from the University of Michigan
documented successful long term control in metastatic adrenocortical adenocarcinoma using
mebendazole 2. Mebendazole was well tolerated at 200 mg/day and used as the sole treatment
after the patient failed other chemotherapies.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
maximum tolerated dose (MTD) of mebendazole
To determine the maximum tolerated dose (MTD) of mebendazole in combination with temozolomide (TMZ) given after surgery and the standard radiation and TMZ treatment in patients with newly diagnosed malignant gliomas.
Gary Gallia, MD
Johns Hopkins University School of Medicine, Department of Neurosurgery
United States: Food and Drug Administration
|The Johs Hopkins Hospital||Baltimore, Maryland 21287|