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

NCT04443049 | Unknown

• 1 other identifier: ILBS-Cirrhosis-32
• Study Type: interventional
• Target: 170
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hepatocellular Carcinoma; Liver Cirrhosis

Outcome Measures

Primary Outcomes (3)

• Overall survival in both groups

  15 months

• Death

  2 year

• Progressive disease requiring change of therapy in both groups

  2 year

Secondary Outcomes (4)

• Progressive disease requiring quitting therapy in both groups

  2 year

• Therapy related adverse effects in both groups

  2 year

• Worsening of performance status in both groups

  2 year

• Decompensation of underlying cirrhosis in both groups

  2 year

Study Arms (2)

Lenvatinib +Placebo

ACTIVE COMPARATOR

Lenvatinib will be given once a day(OD) orally at dose of 8 mg if body weight is \< 60 kg and 12 mg if body weight is \> 60 kg ) with placebo (Tab Mecovit) orally twice a day (BD) daily

Drug: Lenvatinib; Other: Placebo

Lenvatinib and mebendazole

EXPERIMENTAL

Lenvatinib will be given orally once a day (OD) at dose of 8 mg if body weight is \< 60 kg and 12 mg if body weight is \> 60 kg) and mebendazole will be given at dose of 100 mg orally twice a day (BD) daily

Drug: Lenvatinib; Drug: Mebendazole

Interventions

Lenvatinib DRUG

Lenvatinib will be given once a day(OD) orally at dose of 8 mg if body weight is \< 60 kg and 12 mg if body weight is \> 60 kg

Lenvatinib +Placebo; Lenvatinib and mebendazole

Mebendazole DRUG

mebendazole will be given at dose of 100 mg orally twice a day (BD) daily

Lenvatinib and mebendazole

Placebo OTHER

Placebo (Tab Mecovit) orally twice a day (BD) daily

Lenvatinib +Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Cirrhosis of Liver with HCC on imaging and/or biopsy or cytology
• Child Pugh A, Child Pugh B \< 8
• Advanced HCC - as defined by BCLC - C
• ECOG Performance Status 1-2
• Adequately controlled blood pressure (BP) with up to 3 antihypertensive agents, defined as BP ≤150/90 millimeters of mercury (mmHg) at screening and no change in antihypertensive therapy within 1 week prior to commencement of intervention.
• Valid Consent
• Age 18-70 years

You may not qualify if:

• Decompensated Cirrhosis
• Child Pugh C, Child Pugh B \> 7
• HCC patients with a curative therapy (RFA/MWA or LT)
• Prior systemic therapies (or) immunotherapy for HCC
• ECOG Performance Status 3-4
• Post Liver transplant HCC recurrence
• Pregnancy

Sponsors & Collaborators

• Institute of Liver and Biliary Sciences, India: lead

Study Sites (1)

Institute of Liver & Biliary Sciences

New Delhi, National Capital Territory of Delhi, 110070, India

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Cirrhosis

Interventions

lenvatinib; Mebendazole

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Central Study Contacts

Dr Navin Kumar, MD

CONTACT

01146300000; navinktanvi10@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2020
• First Posted: June 23, 2020
• Study Start: July 10, 2020
• Primary Completion: June 19, 2022
• Study Completion: June 19, 2022
• Last Updated: October 5, 2021

Record last verified: 2021-10

Locations

IN (1)