Trial Title:
Combined TACE, TKI/Anti-VEGF and ICIs as Conversion Therapy for Advanced Hepatocellular Carcinoma
NCT ID:
NCT05717738
Condition:
Hepatocellular Carcinoma Non-resectable
Conditions: Official terms:
Carcinoma
Carcinoma, Hepatocellular
Bevacizumab
Atezolizumab
Sorafenib
Apatinib
Lenvatinib
Immune Checkpoint Inhibitors
Antibodies
Antibodies, Monoclonal
Conditions: Keywords:
Hepatocellular Carcinoma
Downstaging conversion therapy
Study type:
Observational
Overall status:
Recruiting
Study design:
Time perspective:
Other
Intervention:
Intervention type:
Procedure
Intervention name:
TACE
Description:
Procedure of TACE is standardized.
Arm group label:
TACE-A-T cohort
Arm group label:
TACE-Apa-C cohort
Arm group label:
TACE-B-S cohort
Arm group label:
TACE-Don-ICI cohort
Arm group label:
TACE-Len-ICI cohort
Arm group label:
TACE-Reg-ICI cohort
Arm group label:
TACE-Sor-ICI cohort
Other name:
transarterial chemoembolization
Intervention type:
Drug
Intervention name:
Lenvatinib
Description:
8mg; p.o.; q.d.
Arm group label:
TACE-Len-ICI cohort
Other name:
levima
Intervention type:
Drug
Intervention name:
Anti-PD-1 monoclonal antibody
Description:
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).
Arm group label:
TACE-Don-ICI cohort
Arm group label:
TACE-Len-ICI cohort
Arm group label:
TACE-Reg-ICI cohort
Arm group label:
TACE-Sor-ICI cohort
Other name:
PD-1 inhibitor
Intervention type:
Drug
Intervention name:
Bevacizumab Biosimilar IBI305 plus sintilimab
Description:
Bevacizumab Biosimilar IBI305 (15mg/kg, q3w), and sintilimab (200 mg, q3w)
Arm group label:
TACE-B-S cohort
Other name:
Byvasda (B) plus S
Intervention type:
Drug
Intervention name:
Bevacizumab plus Atezolizumab
Description:
Bevacizumab (15mg/kg, q3w) plus Atezolizumab (1200 mg, q3w)
Arm group label:
TACE-A-T cohort
Other name:
Avastin plus Tecentriq
Intervention type:
Drug
Intervention name:
apatinib plus camrelizumab
Description:
Apatinib(250 mg; p.o.; q. d.); camrelizumab (200 mg; iv drip; q2w)
Arm group label:
TACE-Apa-C cohort
Other name:
Apa plus C
Intervention type:
Drug
Intervention name:
Sorafenib
Description:
400mg; p.o. bid
Arm group label:
TACE-Sor-ICI cohort
Other name:
Nexavar
Intervention type:
Drug
Intervention name:
Donafenib
Description:
200mg; p.o. bid
Arm group label:
TACE-Don-ICI cohort
Other name:
Zepsun
Intervention type:
Drug
Intervention name:
Regorafenib
Description:
160 mg; p.o.; q.d.
Arm group label:
TACE-Reg-ICI cohort
Other name:
stivarga
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.
Criteria for eligibility:
Study pop:
Patients with advanced hepatocellular carcinoma which initially unsuitable for the
radical therapy, including resection, transplantation, or ablation.
Sampling method:
Non-Probability Sample
Criteria:
Inclusion Criteria:
1. Age ≥ 18 years old
2. 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;
3. at least one measurable lesion according to Response Evaluation Criteria in Solid
Tumors (RECIST) v1.1 or mRESIST criteria.
4. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
5. 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.
6. 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.
7. hepatic vein invasion (VV1 to VV2) were allowed.
8. 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
9. Child-Pugh liver function class A-B7
10. 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.
11. Adequate organ and marrow function, as defined below:
(1) Hemoglobin ≥80 g/L (2) Absolute neutrophil count ≥1.5 ×109/L (3) Platelet count ≥50
×109/L (4) Total bilirubin < 51 μmol/L (5) Alanine transaminase (ALT) and
aminotransferase (AST)≤5×ULN (6) Albumin ≥28 g/L (7) INR ≤1.6 (8) Serum creatinine < 110
μmol/L 12. Time interval between TACE and systemic therapy within 7 days.
Exclusion Criteria:
1. 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 2. Severe, active and uncontrolled co-morbidity including but not limited to:
1. Persistent or activity (except the HBV and HCV) infection;
2. symptoms of congestive heart failure and uncontrolled diabetes;
3. uncontrolled hypertension, systolic pressure ≥ 160 mmHg or diastolic pressure ≥ 100
mmHg despite anti-hypertension medications ≤ 28 days before randomization or first
dose of drug.
4. unstable angina,
5. uncontrolled arrhythmias,
6. active ILD,
7. severe chronic GI disease accompanied by diarrhea,
8. 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.
9. A history of active primary immunodeficiency or human immunodeficiency virus; (10)
Active or previous records of autoimmune disease or inflammatory diseases, including
inflammatory bowel disease (e.g., colitis or Crohn's disease], diverticulitis,
except [diverticulosis], systemic lupus erythematosus (SLE), sarcoidosis syndrome or
Wegener syndrome (e.g., granulomatous vasculitis, gray's disease, rheumatoid
arthritis, the pituitary gland inflammation and uveitis]).
(11) A history of hepatic decompensation, including refractory ascites, gastrointestinal
bleeding, or hepatic encephalopathy; 3. Known to produce allergic or hypersensitive
reactions to any study drug or any excipient thereof; 4. Significant clinical
gastrointestinal bleeding or a potential risk of bleeding was identified by the
investigator during the 30 days prior to study entry.
5. Tumors of the central nervous system, including metastatic brain tumors; 6. Pregnant
women or breast-feeding patients; 7. Has received anti-tumor system therapy for HCC.
Non-anti-tumor purpose combined hormone therapy (e.g., hormone replacement therapy)
is excluded.
8. Is currently using, or has used an immunosuppressive drug within 14 days prior to
the first dose of the investigational drug. This standard has the following
exceptions: (1) intranasal, inhaled, topical or topical steroids. (e.g.,
intraarticular) (2) Systemic corticosteroid therapy not exceeding 10 mg/ day of
prednisone; (3) prophylactic use of steroids for hypersensitivity. (e.g., CT scan
pretherapy medication) 9. A live attenuated vaccine was administered within 30 days
prior to the first administration of the study drug. Note: If enrolled, patients
shall not receive live attenuated vaccine within 30 days of receiving study drug
therapy and after the last administration of study drug.
10. Extrahepatic vascular involvement or thrombosis: main trunk of portal vein and
superior mesenteric vein (Cheng's type III and IV) or inferior vena cava (IVC)
(VV3).
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
The Second Affiliated Hospital of Fujian Medical University
Address:
City:
Quanzhou
Country:
China
Status:
Recruiting
Contact:
Last name:
Yan-jun Wang, M.D.
Phone:
+86-15872415556
Email:
wangyanjun@fjmu.edu.cn
Facility:
Name:
Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Address:
City:
Wuhan
Zip:
430030
Country:
China
Status:
Recruiting
Contact:
Last name:
Ze-yang Ding, M.D.
Facility:
Name:
Optical Valley branch of Tongji hospital
Address:
City:
Wuhan
Zip:
430073
Country:
China
Status:
Recruiting
Contact:
Last name:
Zhanguo Zhang, M.D.
Facility:
Name:
Sino-French branch of Tongji hospital
Address:
City:
Wuhan
Country:
China
Status:
Recruiting
Contact:
Last name:
Ganxun Li, M.D.
Start date:
January 20, 2022
Completion date:
December 31, 2024
Lead sponsor:
Agency:
Tongji Hospital
Agency class:
Other
Collaborator:
Agency:
Chinese Cooperative Group of Liver Cancer
Agency class:
Other
Collaborator:
Agency:
Chen Xiao-ping Foundation for the Development of Science and Technology of Hubei Province
Agency class:
Other
Collaborator:
Agency:
The Second Affiliated Hospital of Fujian Medical University
Agency class:
Other
Collaborator:
Agency:
Geneplus-Beijing Co. Ltd.
Agency class:
Industry
Collaborator:
Agency:
Haplox Biotechnology Co., Ltd.
Agency class:
Industry
Source:
Tongji Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05717738
