To Study the Effects of Addition of Mebendazole to Lenvatinib in Cirrhotics With Advanced Hepatocellular Carcinoma.
Status:
Recruiting
Trial end date:
2022-06-19
Target enrollment:
Participant gender:
Summary
Currently the available first line palliative therapy for advanced HCC is Sorafenib and
Lenvatinib of which Lenvatinib is tolerated better. Unfortunately, patients tend to progress
after few months of therapy. Therefore it is imperative, to do trials by combinative therapy
to the available therapy for added survival benefits and quality of life with advanced HCC.
In this regard, Mebendazole appears to be a good choice for drug repurposing as it has shown
very promising results either alone or in combination with other therapies in tumors of GI
origin and CNS tumors. With regard to HCC Mebendazole has been found to be effective in vitro
system of HCC and preclinical models. However no clinical trials have been initiated till
now. The key hallmark features of HCC include activation of MAPK and angiogenesis which in
turn are targeted by RTK inhibitors such as Sorafenib and Lenvatinib. In this regard
Mebendazole has broad range of action by not only inhibiting angiogenesis and pro-survival
pathways of MAPK, but by also inhibiting the secretion of MMPs and Tubulin polymerization
which can all be beneficial in tumor regression and prevention of chemo-resistance in HCC.
Mounting of a strong immune response plays an important role in identification of tumor
antigen and thereby clearing of tumors. While Mebendazole can modulate the tumor, the data is
scant with respect to the role of the drug. Hence repurposing Mebendazole as a combinatorial
therapy appears a promising approach and forms the basis of the present work. We hypothesize
that combinatorial therapy of addition of mebendazole to lenvatinib will prove more
beneficial than lenvatinib alone in increasing the overall survival of patients with advanced
HCC. To prove the mechanistic effects of mebendazole on HCC, we will also conduct a animal
study in preclinical mice model of HCC with the help of our animal house facility. The animal
study will help us to understand the additional benefits from mebendazole and lenvatinib with
objective evidence of liver biopsy which is not feasible in humans.