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Gastrointestinal Diseases

Liver Diseases

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Antibodies, Monoclonal

Lenvatinib

Bevacizumab

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Sorafenib

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Tyrosine

Patients with advanced hepatocellular carcinoma who was initially evaluated unsuitable for the radical therapy and received combined TACE plus lenvatinib (Len) and anti-PD-1 antibody as conversion therapy for downstaging.

Patients with advanced hepatocellular carcinoma who was initially evaluated unsuitable for the radical therapy and received combined TACE plus bevacizumab (A) and atezolizumab (T) as conversion therapy for downstaging.

Patients with advanced hepatocellular carcinoma who was initially evaluated unsuitable for the radical therapy and received combined TACE plus bevacizumab biosimilar (Byvasda, B) and Sintilimab (Tyvyt, S) antibody as conversion therapy for downstaging.

Patients with advanced hepatocellular carcinoma who was initially evaluated unsuitable for the radical therapy and received combined TACE plus Apatinib (Apa) and Camrelizumab (C) antibody as conversion therapy for downstaging.

Patients with advanced hepatocellular carcinoma who was initially evaluated unsuitable for the radical therapy and received combined TACE plus sorafenib (Sor) and anti-PD-1 antibody as conversion therapy for downstaging.

Patients with advanced hepatocellular carcinoma who was initially evaluated unsuitable for the radical therapy and received combined TACE plus donafenib (Don) and anti-PD-1 antibody as conversion therapy for downstaging.

Patients with advanced hepatocellular carcinoma who was initially evaluated unsuitable for the radical therapy and received combined TACE plus regorafenib (Reg) and anti-PD-1 antibody as conversion therapy for downstaging.

TACE

Advanced HCC Patients treated with TKI plus anti-PD-1 monoclonal antibody as systemic therapy were recruited. Anti-PD-1 monoclonal antibodies include pembrolizumab (200 mg, q3w), nivolumab (3mg/kg, q2w), camrelizumab (200mg, q2w), tislelizumab (200mg, q3w), sintilimab (200 mg, q3w), or toripalimab (240mg, q3w).

Anti-PD-1 monoclonal antibody

Bevacizumab Biosimilar IBI305 (15mg/kg, q3w), and sintilimab (200 mg, q3w)

Bevacizumab Biosimilar IBI305 plus sintilimab

Bevacizumab (15mg/kg, q3w) plus Atezolizumab (1200 mg, q3w)

Bevacizumab plus Atezolizumab

Apatinib(250 mg; p.o.; q. d.); camrelizumab (200 mg; iv drip; q2w)

apatinib plus camrelizumab

Donafenib

Regorafenib

Ze-yang Ding, M.D.

Yan-jun Wang, M.D.

Zhanguo Zhang, M.D.

Ganxun Li, M.D.

The aim of this study is to the efficacy, prognosis, adverse effects, and factors for predicting therapeutic effects and clinical prognosis of combined therapy of transarterial chemoembolization (TACE), Anti-VEGF antibodies or pan-target anti-angiogenic drugs, and anti-PD-1/ PD-L1 antibody for advanced hepatocellular carcinoma which initially unsuitable for the radical therapy, including resection, transplantation, or ablation.

The multicenter, non-random, open and ambispective real-world cohort study is conducted at 4 research centers, including 3 centers (Hankou, Sino-French New District, and Optical Valley) of Tongji hospital (Wuhan, China) and one in the second affiliated hospital of Fujian Medical University (Quanzhou, China). It is estimated that 300 patients with advanced HCC will be enrolled in these 4 research centers. And it is planned to complete the enrollment within 1 year and it is expected that all enrolled subjects will reach the observation end point in 3 years. Radiological assessments are performed every two cycles over the course of treatment, then every 3 months within the first two years following the completion of treatment and every 6 months thereafter, until PD were recorded. All subjects are followed until death or lost to follow up.

Tissue, blood, urine, and feces. Part of cancer tissue and blood samples are utilized for high-throughput sequencing.

Combined TACE, TKI/Anti-VEGF and ICIs as Conversion Therapy for Advanced Hepatocellular Carcinoma

Combined Transarterial Chemoembolization, Tyrosine Kinase Inhibitor/ Anti-VEGF Antibody, and Anti-PD-1/ PD-L1 Antibody as Conversion Therapy for Advanced Hepatocellular Carcinoma: a Multicenters, Real-world, Ambispective Cohort Study

Number of patients amendable to curative surgical interventions defined as number of patients receiving curative surgical resection, transplantation, or ablation after successful down-sizing of tumor(s) by intervention.

Complete response (CR): Disappearance of any intra-tumoral arterial enhancement in all target lesions; Partial response (PR): At least a 30% decrease in the sum of diameters of viable (enhancement in the arterial phase) target lesions, taking as reference the baseline sum of the diameters of target lesions.

Response rate is the rate of CR plus PR.

Time to progression (TTP): measured from the date of first treatment to radiographically documented progression according to mRECIST 1.1. This does not include death from any cause.

Time to intrahepatic tumor progression (TTITP): measured from the date of first treatment to radiographically documented intrahepatic tumor progression according to mRECIST 1.1. This does not include death from any cause.

measured from the date of first treatment to radiographically documented progression according to mRECIST 1.1 or death from any cause (whichever occurs first). Participants alive and without disease progression or lost to follow-up will be censored at the date of their last radiographic assessment.

measured from date of first treatment to the date of death from any cause. Participants alive or lost to follow-up will be censored at the date of their last visit.

Incidence, nature, and severity of adverse events graded according to the United States National Cancer Institute The Common Terminology Criteria for Adverse Events (NCI-CTCAE 5.0).

Pathological response is assessed as the percentage of surface with non-viable cancer cells (represented by necrosis or fibrosis, the ultimate stage of necrosis) in relation to the total tumor area and will be equal to: 100% - viable cancer cells (%). If there are multiple tumors, the mean percentage will be used. Pathological complete response (pCR) is defined by the absence of viable tumor cells in any nodule.

Percentage of patients that had a CR, PR, or SD ≥ 6 months per mRECIST1.1.

Defined as the time from first documented evidence of CR or PR until the first documented sign of disease progression (PD) or death from any cause.

The life quality of every subject is assessed every 3 months during follow up according to the 45-item FACT-Hep questionnaire, which assesses generic HRQL concerns and disease-specific issues.

Chinese Cooperative Group of Liver Cancer

Chen Xiao-ping Foundation for the Development of Science and Technology of Hubei Province

The Second Affiliated Hospital of Fujian Medical University

Geneplus-Beijing Co. Ltd.

Haplox Biotechnology Co., Ltd.

Tongji Hospital

Associate Professor

Micronutrients

Hematinics

Oxaliplatin

Leucovorin

Fluorouracil

Liver Extracts

Patients with advanced hepatocellular carcinoma who was initially evaluated unsuitable for the radical therapy and received combined HAIC plus bevacizumab (A) and atezolizumab (T) as conversion therapy for downstaging.

Patients with advanced hepatocellular carcinoma who was initially evaluated unsuitable for the radical therapy and received combined HAIC plus lenvatinib (Len) and anti-PD-1 antibody as conversion therapy for downstaging.

Patients with advanced hepatocellular carcinoma who was initially evaluated unsuitable for the radical therapy and received combined HAIC plus bevacizumab biosimilar (Byvasda, B) and Sintilimab (Tyvyt, S) antibody as conversion therapy for downstaging.

Patients with advanced hepatocellular carcinoma who was initially evaluated unsuitable for the radical therapy and received combined HAIC plus Apatinib (Apa) and Camrelizumab (C) antibody as conversion therapy for downstaging.

Patients with advanced hepatocellular carcinoma who was initially evaluated unsuitable for the radical therapy and received combined HAIC plus sorafenib (Sor) and anti-PD-1 antibody as conversion therapy for downstaging.

Patients with advanced hepatocellular carcinoma who was initially evaluated unsuitable for the radical therapy and received combined HAIC plus donafenib (Don) and anti-PD-1 antibody as conversion therapy for downstaging.

Patients with advanced hepatocellular carcinoma who was initially evaluated unsuitable for the radical therapy and received combined HAIC plus regorafenib (Reg) and anti-PD-1 antibody as conversion therapy for downstaging.

administration of oxaliplatin , fluorouracil, and leucovorin via the tumor feeding arteries every 3 weeks.

HAIC

HCC Patients treated with TKI plus anti-PD-1 monoclonal antibody as systemic therapy were recruited. Anti-PD-1 monoclonal antibodies include pembrolizumab (200 mg, q3w), nivolumab (3mg/kg, q2w), camrelizumab (200mg, q2w), tislelizumab (200mg, q3w), sintilimab (200 mg, q3w), or toripalimab (240mg, q3w).

ZeYang Ding, M.D.

Jianping Zhao, M.D.

Xin Luo, M.D.

Wanguang Zhang, M.D.

This study is conducted to evaluate the efficacy, prognosis, adverse effects, and factors for predicting therapeutic effects and clinical prognosis of combined therapy of hepatic artery infusion chemotherapy (HAIC), tyrosine kinase inhibitor/ anti-VEGF antibody, and anti-PD-1/ PD-L1 antibody for advanced hepatocellular carcinoma which initially unsuitable for the radical therapy, including resection, transplantation, or ablation. Factors are collected in preoperative routine blood examination, preoperative radiological imaging and pathological examination.

As a local interventional treatment, hepatic arterial infusion chemotherapy (HAIC) has shown better efficacy and safety than traditional transcatheter arterial chemoembolization (TACE) in the treatment of unresectable HCC. In addition, HAIC has been widely used as an alternative to sorafenib in advanced HCC in the eastern Asia. Systemic therapies such as tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs), as well as the combined use of anti-VEGF antibody and ICIs have shown promising results in the treatment of advanced HCC. Numerous studies have shown that combination therapy has a trend toward better tumor response rates, survival outcomes, and downstaging rate to monotherapy.

This study is conducted by the by Chinese Collaborative Group of Liver Cancer (CCGLC), the Chinese Chapter of the International Hepato-Pancreato-Biliary Association (CC-IHPBA). It is estimated that 300 patients with advanced hepatocellular carcinoma will be enrolled in about 4 research centers. And it is planned to complete the enrollment within 1 year and it is expected that all enrolled subjects will reach the observation end point in 3 years.

Combined HAIC, TKI/Anti-VEGF and ICIs as Conversion Therapy for Unresectable Hepatocellular Carcinoma

Combined Hepatic Arterial Infusion Chemotherapy, Tyrosine Kinase Inhibitor/ Anti-VEGF Antibody, and Anti-PD-1/ PD-L1 Antibody as Conversion Therapy for Unresectable Hepatocellular Carcinoma

Complete response (CR): Disappearance of any intra-tumoral arterial enhancement in all target lesions; Partial response (PR): At least a 30% decrease in the sum of diameters of viable (enhancement in the arterial phase) target lesions, taking as reference the baseline sum of the diameters of target lesions; Stable disease (SD): Any cases that do not qualify for either partial response or progressive disease; Progressive disease (PD): An increase of at least 20% in the sum of the diameters of viable (enhancing) target lesions, taking as reference the smallest sum of the diameters of viable (enhancing) target lesions recorded since treatment started.

ORR=CR+PR.

Overall survival (OS): measured from date of first treatment to the date of death from any cause. Participants alive or lost to follow-up will be censored at the date of their last visit.

Incidence, nature, and severity of adverse events graded according to the United States National Cancer Institute The Common Terminology Criteria for Adverse Events (NCI-CTCAE 5.0)

Pathological response is assessed as the percentage of surface with non-viable cancer cells (represented by necrosis or fibrosis, the ultimate stage of necrosis) in relation to the total tumor area and will be equal to: 100% - viable cancer cells (%). If there are multiple tumors, the mean percentage will be used.

Percentage of patients that had a CR, PR, or SD ≥ 6 months per mRECIST

Defined as the time from first documented evidence of CR or PR until the first documented sign of disease progression (PD) or death from any cause

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Combined TACE, TKI/Anti-VEGF and ICIs as Conversion Therapy for Advanced Hepatocellular Carcinoma	NCT05717738	Hepatocellular ...	TACE Lenvatinib Anti-PD-1 monoc... Bevacizumab Bio... Bevacizumab plu... apatinib plus c... Sorafenib Donafenib Regorafenib	18 Years -	Tongji Hospital
Combined TACE, TKI/Anti-VEGF and ICIs as Conversion Therapy for Advanced Hepatocellular Carcinoma	NCT05717738	Hepatocellular ...	TACE Lenvatinib Anti-PD-1 monoc... Bevacizumab Bio... Bevacizumab plu... apatinib plus c... Sorafenib Donafenib Regorafenib	18 Years -	Tongji Hospital
Combined HAIC, TKI/Anti-VEGF and ICIs as Conversion Therapy for Unresectable Hepatocellular Carcinoma	NCT05713994	Hepatocellular ...	HAIC Bevacizumab plu... Bevacizumab Bio... Lenvatinib Sorafenib Donafenib Regorafenib apatinib plus c... Anti-PD-1 monoc...	18 Years -	Tongji Hospital
Combined HAIC, TKI/Anti-VEGF and ICIs as Conversion Therapy for Unresectable Hepatocellular Carcinoma	NCT05713994	Hepatocellular ...	HAIC Bevacizumab plu... Bevacizumab Bio... Lenvatinib Sorafenib Donafenib Regorafenib apatinib plus c... Anti-PD-1 monoc...	18 Years -	Tongji Hospital
Combined TACE, TKI/Anti-VEGF and ICIs as Conversion Therapy for Advanced Hepatocellular Carcinoma	NCT05717738	Hepatocellular ...	TACE Lenvatinib Anti-PD-1 monoc... Bevacizumab Bio... Bevacizumab plu... apatinib plus c... Sorafenib Donafenib Regorafenib	18 Years -	Tongji Hospital

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