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Allied Journal of Medical Research

Volume 2

Page 48

allied

academies

CANCER THERAPY AND ONCOLOGY

NEUROLOGY AND BRAIN DISORDERS

International Conference on

J u n e 2 1 - 2 2 , 2 0 1 8 | O s a k a , J a p a n

Joint Event on

PHASE I/IIA TRIALS IN GBM PATIENTS USING A NEW DRUG

(CEREBRACA WAFER) TARGETING AXL RECEPTOR TYROSINE

KINASE

Shinn Zong (John) Lin

Hualien Tzu Chi Hospital, Taiwan

alignant brain glioma is a highly invasive disease with a very high death rate. The effective treatment method for

this disease is still an unmet medical need. In our previous reports, a pure compound EF-001 showed activities to

arrest the growth and initiate apoptosis of malignant brain glioma. To overcome the limitation of the blood-brain barrier,

a local-release system with EF-001 incorporated into a biodegradable polyanhydride material, p(CPP-SA), was developed

and named “Cerebraca Wafer”. Both the

in vitro

and the

in vivo

release kinetics of the Cerebraca Wafers have been

characterized. The

in situ

therapeutic effects of the Cerebraca Wafer on brain gliomas were demonstrated by FGF-SV40

transgenic mice and orthotopic brain tumor F344 rat models. Signi cant effects on the inhibition of tumor growth and

the increase of survival rate by Cerebraca Wafer implantations were observed, with no signi cant adverse effects on the

rodents. Mechanisms involved in the antitumor effect of EF-001, downstream of AXL receptor tyrosine kinase, including the

up-regulation of Nurr77 by PKC, the repression of human telomerase reverse transcriptase (hTERT) transcriptional activity

via down-regulating Sp1 expression, and the down-regulation of the S-phase kinase-associated protein 2 (Skp2) which

resulted in the brain tumor senescence, were also investigated in the study. The toxicity studies and the PIC/s GMP grade

Cerebraca Wafer production for clinical trials were accomplished. IND (investigational New Drug) application for the Phase

I/IIa clinical trials aiming to determine the safety and the efficacy of Cerebraca Wafer implantation on the recurrent GBM

patients have been approved by USFDA and TFDA at 2016. The trial is now being performed at Hualien Tzu-Chi hospital and

Tri-Service General hospital, with the first Wafer implantation surgery completed at the end of 2017. The preliminary results

for the first three trial patients will be presented and discussed.

Allied J Med Res 2018, Volume 2