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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04443049
Recruitment Status : Recruiting
First Posted : June 23, 2020
Last Update Posted : September 3, 2020
Sponsor:
Information provided by (Responsible Party):
Institute of Liver and Biliary Sciences, India

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.

Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma Liver Cirrhosis Drug: Lenvatinib Drug: Mebendazole Other: Placebo Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 170 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: To Study the Effects of Addition of Mebendazole to Lenvatinib in Cirrhotics With Advanced Hepatocellular Carcinoma.
Actual Study Start Date : July 10, 2020
Estimated Primary Completion Date : June 19, 2022
Estimated Study Completion Date : June 19, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Lenvatinib +Placebo
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
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

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

Experimental: Lenvatinib and mebendazole
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
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

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




Primary Outcome Measures :
  1. Overall survival in both groups [ Time Frame: 15 months ]
  2. Death [ Time Frame: 2 year ]
  3. Progressive disease requiring change of therapy in both groups [ Time Frame: 2 year ]

Secondary Outcome Measures :
  1. Progressive disease requiring quitting therapy in both groups [ Time Frame: 2 year ]
  2. Therapy related adverse effects in both groups [ Time Frame: 2 year ]
  3. Worsening of performance status in both groups [ Time Frame: 2 year ]
    Worsening of performance will be measured by Eastern Cooperative Oncology Group (ECOG) Criteria.

  4. Decompensation of underlying cirrhosis in both groups [ Time Frame: 2 year ]
    Barcelona-Clinic Liver Cancer (BCLC) staging classification will be used.



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04443049


Contacts
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Contact: Dr Navin Kumar, MD 01146300000 navinktanvi10@gmail.com

Locations
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India
Institute of Liver & Biliary Sciences Recruiting
New Delhi, Delhi, India, 110070
Contact: Dr Naveen Kumar, MD    01146300000    navinktanvi10@gmail.com   
Sponsors and Collaborators
Institute of Liver and Biliary Sciences, India
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Responsible Party: Institute of Liver and Biliary Sciences, India
ClinicalTrials.gov Identifier: NCT04443049    
Other Study ID Numbers: ILBS-Cirrhosis-32
First Posted: June 23, 2020    Key Record Dates
Last Update Posted: September 3, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Hepatocellular
Liver Cirrhosis
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Mebendazole
Piperazine
Piperazine citrate
Lenvatinib
DMP 777
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antinematodal Agents
Anthelmintics
Antiparasitic Agents
Anti-Infective Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators