NCT04443049

To Study the Effects of Addition of Mebendazole to Lenvatinib in Cirrhotics With Advanced Hepatocellular Carcinoma.

Status unknown NA Last updated 5 October 2021

What this trial tests

NA trial testing Lenvatinib in Hepatocellular Carcinoma in 170 participants. Status unknown.

Timeline

10 July 2020

Primary endpoint
19 June 2022

19 June 2022

Quick facts

Lead sponsor	Institute of Liver and Biliary Sciences, India
Phase	NA
Status	Status unknown
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	170
Start date	10 July 2020
Primary completion	19 June 2022
Estimated completion	19 June 2022
Sites	1 location across India

Drugs / interventions tested

• Lenvatinib (LENVATINIB) — full drug profile →
• Mebendazole (MEBENDAZOLE) — full drug profile →
• Placebo

Conditions studied

• Hepatocellular Carcinoma — all drugs for Hepatocellular Carcinoma →
• Liver Cirrhosis — all drugs for Liver Cirrhosis →

Sponsor

Institute of Liver and Biliary Sciences, India

Who can join

Adults 18 to 70, any sex, with Hepatocellular Carcinoma or Liver Cirrhosis. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

4 peer-reviewed publications reference this trial (live from Europe PMC):

1. Interplay of Ferroptosis and Cuproptosis in Cancer: Dissecting Metal-Driven Mechanisms for Therapeutic Potentials.
   Wang J, Li J, Liu J, Chan KY, et al · · 2024 · cited 33× · PMID 38339263 · DOI 10.3390/cancers16030512
2. Repurposing of Benzimidazole Anthelmintic Drugs as Cancer Therapeutics.
   Song B, Park EY, Kim KJ, Ki SH. · · 2022 · cited 25× · PMID 36230527 · DOI 10.3390/cancers14194601
3. Drug Repurposing to Enhance Antitumor Response to PD-1/PD-L1 Immune Checkpoint Inhibitors.
   Thuru X, Magnez R, El-Bouazzati H, Vergoten G, et al · · 2022 · cited 10× · PMID 35884428 · DOI 10.3390/cancers14143368
4. Critical dysregulated signaling pathways in drug resistance: highlighting the repositioning of mebendazole for cancer therapy.
   Aliabadi A, Moradi SZ, Abdian S, Fakhri S, et al · · 2025 · PMID 40786044 · DOI 10.3389/fphar.2025.1631419