Lenvatinib Combined With Gefitinib in the Treatment of Lenvatinib-resistant Hepatocellular Carcinoma

NCT04642547 | Completed DMC

• 1 other identifier: RJZLJRZB
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective clinical study aiming to tests the safety and efficacy of lenvatinib in combination with gefitinib in people with lenvatinib resistant hepatocellular carcinoma. This study will help find out if lenvatinib and gefitinib is a safe and useful combination for treating patients with lenvatinib resistant hepatocellular carcinoma.

Conditions

Hepatocellular Carcinoma; Molecular Targeted Therapy

Keywords

hepatocellular carcinoma; lenvatinib; gefitinib

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  The estimation of time from start of combination therapy to progression of disease

  6 months after the last subject is enrolled

Secondary Outcomes (2)

• Overall survival

  6 months after the last subject is enrolled

• Safety endpoint

  6 months after the last subject is enrolled

Study Arms (1)

Combination therapy with Lenvatinib and Gefitinib

EXPERIMENTAL

First week: Gefitinib 125mg/day, Lenvatinib 8mg/day if body weight ≤ 60Kg and 12mg/day if body weight \> 60Kg. If the patient is well tolerated, the dose of Gefitinib will be adjusted to 250 mg/day after one week, and the dose of Lenvatinib will remain the same (8mg/day for weight ≤ 60Kg and 12mg/day for weight \> 60Kg). Route of administration: Oral.

Drug: Lenvatinib and Gefitinib

Interventions

Lenvatinib and Gefitinib DRUG

First week: Gefitinib: 125mg/day, oral; Lenvatinib: 8mg/day (weight ≤ 60Kg) or 12mg/day (weight \> 60Kg), oral. One week later: Gefitinib: 250mg/day, oral; Lenvatinib: 8mg/day (weight ≤ 60Kg) or 12mg/day (weight \> 60Kg), oral.

Combination therapy with Lenvatinib and Gefitinib

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• (1) Unlimited gender, aged 18-75 years; (2) Meets American Association for the Study of Liver Diseases (AASLD) or European Association for the Study of the Liver (EASL) clinical diagnostic criteria of hepatocellular carcinoma; (3) Barcelona Clinic Liver Cancer (BCLC) Stage B or C, and there is at least one measurable tumor in the liver (long diameter ≥ 1cm);(4) progressing after standard treatment; (5) Unresponsive or resistant to Lenvatinib; (6) Child-Pugh A or scored 7 B; (7) Eastern Cooperative Oncology Group performance status score \<= 1; (8) Platelet count \>= 60x10\^9/L, Prothrombin time prolonged \<= 6 seconds.

You may not qualify if:

• (1) Uncorrectable coagulopathy with obvious bleeding tendency; (2) Patients need long-term anticoagulant or anti platelet therapy and cannot stop the drugs; (3) Patients with unstable or active ulcer or gastrointestinal bleeding; (4) Heart disease requiring treatment or not well controlled high blood pressure; (5) Patients with interstitial pneumonia; (6) Hepatic encephalopathy or refractory ascites requiring treatment; (7) There is a clear active infection; (8) Receiving radiotherapy/chemotherapy/interventional therapy for tumor within 4 weeks before the start of the study; (9) Severe insufficiency of important organs, such as severe cardiopulmonary insufficiency; (10) Other accompanying anti-tumor treatments; (11) The investigator assessed that the patient was unable or unwilling to comply with the protocol.

Sponsors & Collaborators

• RenJi Hospital: lead

Study Sites (1)

Renji Hospital, School of Medicine, Shanghai Jiaotong University

Shanghai, Shanghai Municipality, 200127, China

Location

Related Publications (2)

• Shi Y, Cui D, Xia L, Shi D, Jin G, Wang S, Lin Y, Tang X, Chi J, Wang T, Li M, Lv Z, Zheng J, Jia Q, Yang W, Sun Z, Yang F, Feng H, Yuan S, Zhou W, Qin W, Bernards R, Jin H, Zhai B. Efficacy and safety of lenvatinib plus gefitinib in lenvatinib-resistant hepatocellular carcinomas: a prospective, single-arm exploratory trial. Signal Transduct Target Ther. 2024 Dec 9;9(1):359. doi: 10.1038/s41392-024-02085-8.

  PMID: 39653700 DERIVED

• Jin H, Shi Y, Lv Y, Yuan S, Ramirez CFA, Lieftink C, Wang L, Wang S, Wang C, Dias MH, Jochems F, Yang Y, Bosma A, Hijmans EM, de Groot MHP, Vegna S, Cui D, Zhou Y, Ling J, Wang H, Guo Y, Zheng X, Isima N, Wu H, Sun C, Beijersbergen RL, Akkari L, Zhou W, Zhai B, Qin W, Bernards R. EGFR activation limits the response of liver cancer to lenvatinib. Nature. 2021 Jul;595(7869):730-734. doi: 10.1038/s41586-021-03741-7. Epub 2021 Jul 21.

  PMID: 34290403 DERIVED

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

lenvatinib; Gefitinib

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)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Bo Zhai, MD&PhD

  Renji Hospital, School of Medicine, Shanghai Jiaotong University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Interventional Oncology Department

Study Record Dates

• First Submitted: November 18, 2020
• First Posted: November 24, 2020
• Study Start: December 2, 2020
• Primary Completion: March 31, 2023
• Study Completion: March 31, 2023
• Last Updated: August 1, 2023

Record last verified: 2023-07

Locations

CN (1)