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
Overview
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Tongji Hospital
- Enrollment
- 300
- Locations
- 4
- Primary Endpoint
- Number of Patients Amendable to Curative Surgical Interventions
Overview
Brief Summary
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.
Detailed Description
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.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Other
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age ≥ 18 years old
- •Diagnosis of HCC is according to the American Association for the Study of Liver Diseases or European Association for the Study of the Liver guidelines of HCC management;
- •at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or mRESIST criteria.
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
- •Hepatocellular carcinoma (HCC) was assessed as not suitable for radical resection, liver transplant, or ablation treatment after the assessment of a multidisciplinary team because either: (1) R0 resection was not feasible; (2) remnant liver volume was less than 30% in patients who did not have cirrhosis or 40% in patients with cirrhosis, or the results of an indocyanine green test were higher than 15%; (3) patients had Barcelona Clinic Liver Cancer (BCLC) stage B or BCLC stage C.
- •portal vein involvement (Chen's groups A, or Cheng's type I-II) is allowed: Chen's group A1 or Cheng's type I, tumor thrombus is involved in segmental or sectoral branches of the portal vein or above; Chen's group A2 or Cheng's type II, involvement of the first branch of portal vein.
- •hepatic vein invasion (VV1 to VV2) were allowed.
- •Patients with extrahepatic oligometastasis is allowed: extrahepatic oligometastasis was defined as up to three metastatic lesions in up to two organs with the largest diameter of 3 cm
- •Child-Pugh liver function class A-B7
- •No prior transplantation, TACE, or radioembolization to the liver was allowed. Prior locoregional therapies, such as surgical resection, radiotherapy, radiofrequency ablation, percutaneous ethanol injection or cryoablation, are allowed if the disease have progressed since prior treatment. Local therapy must have been completed at least 4 weeks prior to the baseline scan.
Exclusion Criteria
- •Prior invasive malignancy within 2 years except for noninvasive malignancies such as cervical carcinoma in situ, in situ prostate cancer, non-melanomatous carcinoma of the skin, lobular or ductal carcinoma in situ of the breast that has been surgically cured
- •Severe, active and uncontrolled co-morbidity including but not limited to:
- •Persistent or activity (except the HBV and HCV) infection;
- •symptoms of congestive heart failure and uncontrolled diabetes;
- •uncontrolled hypertension, systolic pressure ≥ 160 mmHg or diastolic pressure ≥ 100 mmHg despite anti-hypertension medications ≤ 28 days before randomization or first dose of drug.
- •unstable angina,
- •uncontrolled arrhythmias,
- •active ILD,
- •severe chronic GI disease accompanied by diarrhea,
- •compliance with requirements may limit the research, resulted in significant increase risk of AE or influence Subjects provided psychiatric/social problem status on their ability to provide written informed consent.
Arms & Interventions
TACE-Len-ICI cohort
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.
Intervention: TACE (Procedure)
TACE-Len-ICI cohort
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.
Intervention: Lenvatinib (Drug)
TACE-Len-ICI cohort
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.
Intervention: Anti-PD-1 monoclonal antibody (Drug)
TACE-A-T cohort
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.
Intervention: TACE (Procedure)
TACE-A-T cohort
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.
Intervention: Bevacizumab plus Atezolizumab (Drug)
TACE-B-S cohort
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.
Intervention: TACE (Procedure)
TACE-B-S cohort
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.
Intervention: Bevacizumab Biosimilar IBI305 plus sintilimab (Drug)
TACE-Apa-C cohort
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.
Intervention: TACE (Procedure)
TACE-Apa-C cohort
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.
Intervention: apatinib plus camrelizumab (Drug)
TACE-Sor-ICI cohort
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.
Intervention: TACE (Procedure)
TACE-Sor-ICI cohort
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.
Intervention: Anti-PD-1 monoclonal antibody (Drug)
TACE-Sor-ICI cohort
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.
Intervention: Sorafenib (Drug)
TACE-Don-ICI cohort
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.
Intervention: TACE (Procedure)
TACE-Don-ICI cohort
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.
Intervention: Anti-PD-1 monoclonal antibody (Drug)
TACE-Don-ICI cohort
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.
Intervention: Donafenib (Drug)
TACE-Reg-ICI cohort
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.
Intervention: TACE (Procedure)
TACE-Reg-ICI cohort
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.
Intervention: Anti-PD-1 monoclonal antibody (Drug)
TACE-Reg-ICI cohort
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.
Intervention: Regorafenib (Drug)
Outcomes
Primary Outcomes
Number of Patients Amendable to Curative Surgical Interventions
Time Frame: from the date of first treatment to the date of last treatment, an average of 3 years
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.
Secondary Outcomes
- Incidence of Study-Related Adverse Events(from the date of first treatment to 90 days after last treatment, around 3 years and 90 days)
- Quality of Life (QoL) after treatment(3 year)
- Pathological response(from the date of first treatment to radiographically documented progression according to mRECIST 1.1 or death from any cause, whichever occurs first, assessed up to 5 years.)
- Progression-free survival (PFS)(from the date of first treatment to radiographically documented progression according to mRECIST 1.1 or death from any cause, whichever occurs first, assessed up to 3 years)
- Overall survival (OS)(from the date of first treatment to the date of death from any cause, assessed up to 5 years)
- Duration of response(from the date of first documented evidence of CR or PR to first documented sign of PD or death from any cause according to mRECIST 1.1, assessed up to 3 years)
- Response Rate measured by mRECIST criteria(from the date of first treatment to radiographically documented progression according to mRECIST v1.1, assessed up to 3 years)
- Time to progression (TTP)(from the date of first treatment to radiographically documented progression according to mRECIST1.1, assessed up to 3 years)
- Time to intrahepatic tumor progression (TTITP)(from the date of first treatment to radiographically documented intrahepatic tumor progression according to mRECIST 1.1, assessed up to 3 years)
- Disease control rate(from the date of first treatment to radiographically documented response according to mRECIST 1.1, assessed up to 3 years.)
Investigators
Ze-yang Ding, MD
Associate Professor
Tongji Hospital