Toripalimab in Combination With Lenvatinib and TACE for Conversion Therapy in Patients With Potentially Resectable HCC

NCT05056337 | Unknown Phase 3 DMC

• 1 other identifier: B2021-338(2)
• Study Type: interventional
• Target: 220
• Locations: 1 country
• Sites: 1

Brief Summary

Study introduction: this is a multicenter, randomized controlled study of patients with histopathologically confirmed hepatocellular carcinoma (HCC) who have not previously received systematic treatment for HCC, all the patients are Chinese stage IIb/IIIa (BCLC stage B/C), and have not developed extrahepatic metastases. Follow-up, data collection and analysis will be performed for patients who meet the study inclusion criteria and will be treated with lenvatinib plus toripalimab and TACE (on demand) or TACE alone, so as to compare the objective response rate (ORR), overall survival (OS), progression-free survival (PFS), ratio of conversion resection, and safety between the two cohorts.

Conditions

Hepatocellular Carcinoma

Keywords

Toripalimab; Lenvatinib; TACE; conversion therapy; HCC

Outcome Measures

Primary Outcomes (1)

• Tumor response: Objective response rate (assessed based on mRECIST criteria)

  Proportion of patients who achieve pre-defined tumor volume reduction and can maintain the minimum time limit, as the sum of complete response (CR) and partial response (PR) ratios (assessed based on mRECIST criteria)

  Up to approximately 36 months

Secondary Outcomes (5)

• Tumor response: Objective response rate (assessed based on RECIST1.1 criteria)

  Up to approximately 36 months

• Overall survival (OS)

  Up to approximately 36 months

• Progression-free survival (PFS)

  Up to approximately 36 months

• Percentage of patients who can receive resection.

  Up to approximately 36 months

• Adverse Events as assessed by CTCAE 5.0 criteria

  Up to approximately 36 months

Study Arms (2)

Treatment group

EXPERIMENTAL

Patients with potentially resectable HCC who meet the study inclusion criteria will be treated with lenvatinib(8mg/d for BW\<60kg and 12mg for BW≥60kg) in combination with toripalimab(240mg iv Q3W) and TACE (on demand). Tumor response will be regularly evaluated, data will be collected, and complete surgical resection will be evaluated by an independent review committee, the conversion resection rate will be calculated, and patient survival will be assessed.

Drug: Lenvatinib 4 MG Oral Capsule [Lenvima]; Drug: Toripalimab; Procedure: TACE

Control group

ACTIVE COMPARATOR

Patients with potentially resectable HCC who meet the study inclusion criteria will be treated with TACE alone. Tumor response will be regularly evaluated, data will be collected, and complete surgical resection will be evaluated by an independent review committee, the translational resection rate will be calculated, and patient survival will be assessed.

Procedure: TACE

Interventions

Lenvatinib 4 MG Oral Capsule [Lenvima] DRUG

patients will be treated with lenvatinib in combination with toripalimab and TACE (on demand)

Treatment group

Toripalimab DRUG

patients will be treated with lenvatinib in combination with toripalimab and TACE (on demand)

Treatment group

TACE PROCEDURE

Hepatic arterial chemoembolization

Control group; Treatment group

Eligibility Criteria

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

You may qualify if:

• Male or female patients of 18-75 years old;
• Clinical or histopathological diagnosis of hepatocellular carcinoma;
• ECOG PS score of 0-1, Child-Pugh grade A;
• Chinese stage IIb/IIIa (equal to BCLC B/C) patients with portal vein tumor thrombus (according to the Japanese PVTT grading criteria Vp3-Vp4) or more than 3 tumor nodules, without extrahepatic metastasis;
• According to the evaluation by the site multi-disciplinary team (MDT), surgical resection is not the current preferred treatment;
• No previous systemic treatment for hepatocellular carcinoma; no previous use of PD-1 inhibitor, PD-L1 inhibitor, lenvatinib or sorafenib;
• Previous TACE treatment for 0-2 times
• The patients in the treatment group voluntarily and have decided to receive treatment of lenvatinib in combination with toripalimab and TACE, and sign an informed consent form. Additional identification of qualified subjects: subjects who have received at least one combination medication enter the safety evaluation; subjects who have received at least one imaging evaluation after treatment enter the efficacy evaluation. The patients in the control group treated with TACE alone have at least one imaging evaluation.
• Patients with HBV infection (characterized by hepatitis B surface antigen \[HBsAg\] positive and/or hepatitis B core antibody \[anti-HBcAb\], with detectable HBV DNA \[\>10 IU/mL\]) should be treated with antiviral therapy according to clinical routine, so as to ensure adequate viral suppression (HBV DNA≤2000 IU/mL or 104) before enrollment. Patients must maintain antiviral therapy during the study period and within 6 months after the last study drug administration; patients with positive hepatitis B core antibody (HBc) and undetectable HBV DNA (\<10 IU/mL) will be not required to receive antiviral therapy before enrollment; these patients will be checked every cycle to monitor HBV DNA levels; if HBV DNA is detected (\> 10 IU/mL), antiviral therapy will be initiated; patients with detectable HBV DNA must continue to receive antiviral therapy during the study

You may not qualify if:

• Clinical or pathological diagnosis of mixed liver cancer, fibrolamellar hepatocellular carcinoma or other non-hepatocellular malignant tumor components;
• Hematological examination: PLT\<50×109/L, WBC\<3.0×109/L or not meet the requirements of TACE treatment;
• Coagulation function: international normalized (prothrombin time) ratio (INR) \> 1.2;
• Liver function indicators: serum albumin (ALB) \< 2.8 g/dl, serum total bilirubin (TBIL) \> 1.5 times the upper limit of normal (excluding those with biliary obstruction), serum transaminase (ALT and AST) \> 3 times the upper limit of normal;
• Renal function indicators: serum creatinine (CR) \> 1.5 times the upper limit of normal;
• Uncontrollable hypertension (defined as diastolic blood pressure \> 90 mmHg or systolic blood pressure \> 150 mmHg);
• Patients with bile duct tumor thrombi, superior mesenteric vein tumor thrombi and diffuse portal vein tumor thrombi;
• Participated in other clinical trials 30 days before screening;
• Accompanied by hepatic encephalopathy, Gilbert syndrome, sclerosing cholangitis, etc.;
• Acute gastrointestinal bleeding recorded within the last 3 months;
• Have a history of allogeneic transplantation (such as liver transplantation);
• Patients with acute or chronic active hepatitis B or C infection, hepatitis B virus (HBV) DNA \> 2000IU/ml or 104 copies/ml; hepatitis C virus (HCV) RNA \> 103 copies/ml; those who are positive for both hepatitis B surface antigen (HbsAg) and anti-HCV antibodies.
• Patients who have autoimmune diseases or a history of autoimmune diseases or syndromes requiring systemic use of steroids / immunosuppressants, including hypophysitis, pneumonia, colitis, hepatitis, nephritis, hyperthyroidism, hypothyroidism etc.
• Be suspected of being allergic to study drugs;
• Patients with other organ dysfunction who are expected to be unable to tolerate general anesthesia or hepatectomy;

Sponsors & Collaborators

• Shanghai Zhongshan Hospital: lead

Study Sites (1)

Fudan University Zhongshan Hospital

Shanghai, Shanghai Municipality, 200000, China

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

lenvatinib; toripalimab

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 17, 2021
• First Posted: September 24, 2021
• Study Start: August 1, 2021
• Primary Completion: November 1, 2023
• Study Completion: December 1, 2023
• Last Updated: September 24, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)