Assessment of the Efficacy of Lenvatinib Versus Sorafenib in the Management of Advanced Hepatocellular Carcinoma

NCT05391867 | Unknown

• 1 other identifier: Sirsalimullah
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 2

Brief Summary

Hepatocellular carcinoma is the most common type of liver cancer, which is the 3rd leading cause of cancer deaths worldwide. The incidence is expected to increase as a consequence of chronic liver disease with its multiple risk factors, including chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, excessive alcohol consumption, nonalcoholic fatty liver disease, hemochromatosis, and aflatoxin B1.It is estimated that 70%-90% of patients with HCC have chronic liver disease and cirrhosis, which limits the feasibility of surgical procedures in advanced cases. There are limited treatment options for HCC patients who are ineligible for surgical resection. Locoregional therapies, such as radiofrequency ablation, transarterial chemoembolization (TACE), transarterial embolization (TAE), or hepatic arterial infusion chemotherapy (HAIC), are primarily recommended, and if one of those fail, then systemic therapy is considered. The 2013 Japan Society of Hepatology HCC Guidelines outlined that the factors influencing treatment decisions should be based on the degree of liver damage (Child-Pugh), presence or absence of extrahepatic spread and macrovascular invasion, the number of tumors, and tumor diameter. Sorafenib has been the standard of care since 2007, when the SHARP trial demonstrated that sorafenib improved median overall survival (OS) compared to placebo in patients who had not received prior systemic therapy (10.7 vs 7.9 months, HR =0.69, P\<0.001). In patients from the Asia-Pacific region taking sorafenib, the median improvement in overall survival compared with placebo was 2.3 months (6.5 months vs 4.2 months; HR 0.68; p=0.014). Drug development for hepatocellular carcinoma in the past 10 years has been marked by four failed global phase 3 trials (of sunitinib, brivanib, linifanib, and erlotinib plus sorafenib) that did not show non-inferiority. Sorafenib, an oral multikinase inhibitor, has been the only systemic therapy demonstrated to extend overall survibility as a firstline treatment, showing a median improvement of 2.8 months compared with placebo (10.7 months vs. 7.9 months; hazard ratio \[HR\] 0.69; p\\0.001).6 Inpatients from the Asia-Pacific region taking sorafenib, the median OS (mOS) improvement compared with placebo was 2.3 months (HR 0.68; p = 0.014). The use of other molecularly targeted agents has not demonstrated efficacy via non-inferiority or superiority to sorafenib; thus, until the appearance of lenvatinib, sorafenib has also been widely used as the first-line treatment for uHCC patients in Japan. Recently, regorafenib and Nivolumab were approved as a second-line systemic treatment for patients who do not respond to the first-line treatments. Otherwise, best supportive care or participation in clinical trials is recommended in the second-line setting by treatment guidelines. Chemotherapy in combination with sorafenib (doxorubicin) and radioembolization with SIR Spheres Y-90 resin microspheres failed to demonstrate a survival benefit or showed a worse safety profile compared to sorafenib in the first-line setting. Eventually, the PhaseIII non-inferiority REFLECT trial showed that lenvatinib was non-inferior compared to sorafenib.

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Overall survivability

  Overall survivability of hepatocellular carcinoma patients will be assessed and compared between two groups (Lenvatinib group vs Sorafenib group)

  From the date of Randomization to next 3 months or till death

Study Arms (2)

Lenvatinib group (Group-A)

EXPERIMENTAL

Patients diagnosed as hepatocellular carcinoma will be randomly assigned for treatment with Lenvatinib. Cap. Lenvatinib will be given at doses of 4 mg 12 hourly.

Drug: Lenvatinib

Sorafenib group (Group-B)

EXPERIMENTAL

Patients diagnosed as hepatocellular carcinoma will be randomly assigned for treatment with Sorafenib. Tab. Sorafenib will be given at doses of 200 mg 12 hourly.

Drug: Lenvatinib

Interventions

Lenvatinib DRUG

Tyrosine kinase inhibitor

Also known as: Sorafenib

Lenvatinib group (Group-A); Sorafenib group (Group-B)

Eligibility Criteria

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

You may qualify if:

• \. Patients with Hepatocellular Carcinoma (Diagnosed histologically or cytologically or by imaging criteria with CT or MRI) with no option of resectibility (BCLC stage B or C) 2. Age ≥ 18 years

You may not qualify if:

• \- 1. Patients with very early stage Hepatocellular Carcinoma (BCLC stage 0) 2. Patients with early stage Hepatocellular Carcinoma (BCLC stage A) 3. Patients with terminal stage Hepatocellular Carcinoma (BCLC stage D) 4. Patients with Hepatocellular Carcinoma with obvious invasion to bile duct. 5. Patients who received previous systemic therapy for Hepatocellular Carcinoma.
• \. Patients with jaundice (serum bilirubin ≥ 3 mg/dl) 8. Patients with aminotransferases ≥ 5ULN 8. Patients with other co-morbid conditions (COPD, CKD, Heart failure, IHD, pregnancy)

Sponsors & Collaborators

• Sir Salimullah Medical College Mitford Hospital: lead

Study Sites (2)

Department of Hepatology

Dhaka, 1100, Bangladesh

NOT YET RECRUITING

Sir Salimullah Medical College

Dhaka, 1100, Bangladesh

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

lenvatinib; Sorafenib

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

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Mohammad S Hossain, MBBS, MD

  Sir Salimullah Medical College

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mohammad S Hossain, MBBS, MD

CONTACT

+8801727626789; romelssmcmh@gmail.com

Md F Karim, MBBS, FCPS, MD

CONTACT

+8801715004634; drfazalkarim@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: An open label randomized clinical trial

Study Record Dates

• First Submitted: November 26, 2020
• First Posted: May 26, 2022
• Study Start: January 1, 2022
• Primary Completion: December 31, 2022
• Study Completion: June 30, 2023
• Last Updated: May 26, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: January' 2021 - December'2021
• Access Criteria: romelssmcmh@gmail.com

Locations

BA (2)