Clinical Study of the Efficacy and Safety of Transhepatic Arterial Chemoembolization Combined With Tislelizumab and Lenvatinib in Patients With Advanced Unresectable Hepatocellular Carcinoma

ICIs combined with AATDs have gradually become the mainstream treatment modality for advanced hepatocellular carcinoma, and more related clinical trials are underway. This is undoubtedly a breakthrough and the main direction for improving the overall 5-year survival rate of the liver cancer population in the next decade, and a touchstone for exploring the development and value of liver surgery in the era of comprehensive treatment for advanced hepatocellular carcinoma.

Overall, there are relatively few reports on various types of translational therapy for advanced HCC, probably for the following two reasons: (1) advanced hepatocellular carcinoma is complex, rapidly progressing, difficult to treat, and has low translational efficiency; (2) the existing translational therapy strategies are highly selective in terms of applicable population, complex treatment process, and institutional dependence, and cannot achieve efficient and successful translation.

At present, there are few studies reported on the application of TACE+ICIs+AATDs to carry out translational therapy. In the absence of relevant guidelines for reference, advanced hepatocellular carcinoma may be the best entrance to carry out translational therapy with ICIs combined with AATDs, and after satisfactory results are achieved in the treatment of this group of patients, a point-to-point effect can be generated, facilitating the transformation of TACE+ICIs+AATDs The target population of TACE+ICIs+AATDs translational therapy can be further expanded. To promote the development of hepatocellular carcinoma treatment and improve the long-term survival rate of the overall hepatocellular carcinoma population. In this study, we enrolled patients with advanced HCC and used TACE+ICIs+AATDs for conversion therapy to improve the conversion rate, so that unresectable HCC patients could be converted to a chronic disease state and achieve long-term survival on the one hand, and provide potential for sequential surgical treatment on the other. The drug of choice is lenvatinib. This study provides a basis for the clinical application of translational therapy for advanced hepatocellular carcinoma.

Study Overview

• Status: Active, not recruiting
• Conditions: TACE; Lenvatinib; Tislelizumab; Advanced Unresectable Hepatocellular Carcinoma
• Intervention / Treatment: Combination product: Tislelizumab and Lenvatinib

• Study Type: Interventional
• Enrollment (Anticipated): 31
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Guangxi
    • Nanning, Guangxi, China, 530000
      • The Affiliated Cancer Hospital of Guangxi Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Advanced Unresectable Hepatocellular Carcinoma
2. Histological examination or clinical diagnosis of HCC
3. BCLC C Stage
4. Child-Pugh A
5. ECOG 0-1
6. Age ≥ 18 years old and ≤ 70 years old
7. No serious concomitant diseases
8. No Portal vein tumor thrombus or Inferior vena cava tumor thrombus
9. No extrahepatic metastases
10. Not receiving any systematic treatment
11. life expectancy > 3 months.
12. The patient must be able to understand and be willing to sign a written informed consent form.

Exclusion Criteria:

1. previous (within 5 years) or concurrent other malignancies
2. participated in a clinical trial of another drug within four weeks
3. the presence of a contraindication to TACE
4. There is a history of bleeding, and any bleeding event with a severe grade of 3 or above in CTCAE v5.0 occurred within 4 weeks before screening
5. Patients with known CNS metastases or a history of CNS metastases prior to screening. For patients with clinically suspected CNS metastases, CT or MRI must be performed within 28 days prior to enrolment to exclude CNS metastases.
6. patients with a history of unstable angina pectoris; those with newly diagnosed angina pectoris within 3 months prior to screening or a myocardial infarction event within 6 months prior to screening; arrhythmias (including QTcF: ≥ 450 ms in men and ≥ 470 ms in women) requiring long-term antiarrhythmic medication and New York Heart Association classification ≥ Class II cardiac insufficiency.
7. Have a history of immunodeficiency, or suffer from other acquired and congenital immunodeficiency diseases, or have received allogeneic stem cell transplantation or organ transplantation in the past.
8. patients with infectious pneumonia, non-infectious pneumonia, interstitial pneumonia and other conditions requiring the use of corticosteroids.
9. Have a serious history of chronic autoimmune diseases, such as systemic lupus erythematosus. Well-controlled immune-related diseases, such as dermatitis, psoriasis and rheumatoid arthritis, can be included in the group after being evaluated by researchers.
10. There is a history of inflammatory bowel diseases such as ulcerative enteritis and Crohn's disease, and a history of inflammatory chronic diarrhea diseases such as irritable bowel syndrome.
11. Have a history of sarcoidosis or tuberculosis.
12. Known history of human immunodeficiency virus (HIV) infection.
13. patients with hypersensitivity to human or murine monoclonal antibodies.
14. persons with a history of psychotropic substance abuse who are unable to abstain or who have a psychiatric disorder.
15. patients with clinical signs of pleural effusion or peritoneal effusion requiring clinical intervention.
16. patients with concomitant illnesses that, in the judgment of the investigator, seriously jeopardize patient safety or interfere with patient completion of the study.
17. pregnant and lactating females.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Patients with advanced unresectable liver cancer

Combination product: Tislelizumab and Lenvatinib; TACE therapy: For transarterial infusion chemotherapy before or after TACE embolization, each drug will generally be diluted with 0.9% sodium chloride solution or 5% dextrose solution 150-250 mL and injected slowly into the target artery for ≥20 min. Subsequent TACE therapy will be administered on an as-needed basis as assessed by the clinician, with each treatment interval exceeding 6 weeks and no more than 6 treatments in total. Lenvatinib: The starting dose of lenvatinib will depend on the patient's baseline weight: if baseline weight ≥ 60 kg, patients will receive 12 mg of lenvatinib administered once daily; if baseline weight < 60 kg, patients will receive 8 mg of lenvatinib once daily. TACE therapy will be given 3 days apart. Tirelizumab: Tirelizumab 200 mg , intravenous infusion on the same day as the first dose of lenvatinib, once every three weeks. Translated with www.DeepL.com/Translator (free version); Other Names: Clinical Study of the Efficacy and Safety of Transhepatic Arterial Chemoembolization Combined With Tislelizumab and Lenvatinib in Patients With Advanced Unresectable Hepatocellular Carcinoma

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate	Refers to cases in which the objective tumor outcome, including CR and PR, was assessed using the mRECIST version of the criteria	1 year

Collaborators and Investigators

• Sponsor: Cancer Hospital of Guangxi Medical University

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): July 5, 2024

Study Registration Dates

• First Submitted: November 4, 2021
• First Submitted That Met QC Criteria: November 12, 2021
• First Posted (Actual): November 23, 2021

Study Record Updates

• Last Update Posted (Estimate): January 26, 2023
• Last Update Submitted That Met QC Criteria: January 25, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Lenvatinib
• Other Study ID Numbers: CS2021（94）

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No