Trial Title:
Combined HAIC, TKI/Anti-VEGF and ICIs as Conversion Therapy for Unresectable Hepatocellular Carcinoma
NCT ID:
NCT05713994
Condition:
Hepatocellular Carcinoma Non-resectable
Conditions: Official terms:
Carcinoma
Carcinoma, Hepatocellular
Bevacizumab
Atezolizumab
Sorafenib
Apatinib
Lenvatinib
Immune Checkpoint Inhibitors
Antibodies
Antibodies, Monoclonal
Conditions: Keywords:
Liver Neoplasms
Hepatocellular Carcinoma
Study type:
Observational
Overall status:
Recruiting
Study design:
Time perspective:
Prospective
Intervention:
Intervention type:
Procedure
Intervention name:
HAIC
Description:
administration of oxaliplatin , fluorouracil, and leucovorin via the tumor feeding
arteries every 3 weeks.
Arm group label:
HAIC-A-T cohort
Arm group label:
HAIC-Apa-C cohort
Arm group label:
HAIC-B-S cohort
Arm group label:
HAIC-Don-ICI cohort
Arm group label:
HAIC-Len-ICI cohort
Arm group label:
HAIC-Reg-ICI cohort
Arm group label:
HAIC-Sor-ICI cohort
Other name:
hepatic arterial infusion chemotherapy of FOLFOX
Intervention type:
Drug
Intervention name:
Bevacizumab plus Atezolizumab
Description:
Bevacizumab (15mg/kg, q3w) plus Atezolizumab (1200 mg, q3w)
Arm group label:
HAIC-A-T cohort
Other name:
Avastin plus Tecentriq
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:
HAIC-B-S cohort
Other name:
Byvasda (B) plus S
Intervention type:
Drug
Intervention name:
Lenvatinib
Description:
8mg; p.o.; q.d.
Arm group label:
HAIC-Len-ICI cohort
Other name:
Lenvima
Intervention type:
Drug
Intervention name:
Sorafenib
Description:
400mg; p.o. bid
Arm group label:
HAIC-Sor-ICI cohort
Other name:
Nexavar
Intervention type:
Drug
Intervention name:
Donafenib
Description:
200mg; p.o. bid
Arm group label:
HAIC-Don-ICI cohort
Other name:
Zepsun
Intervention type:
Drug
Intervention name:
Regorafenib
Description:
160 mg; p.o.; q.d.
Arm group label:
HAIC-Reg-ICI cohort
Other name:
stivarga
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:
HAIC-Apa-C cohort
Other name:
Apa plus C
Intervention type:
Drug
Intervention name:
Anti-PD-1 monoclonal antibody
Description:
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:
HAIC-Don-ICI cohort
Arm group label:
HAIC-Len-ICI cohort
Arm group label:
HAIC-Reg-ICI cohort
Arm group label:
HAIC-Sor-ICI cohort
Other name:
PD-1 inhibitor
Summary:
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.
Detailed description:
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.
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 and beyond Up-to-seven
criteria; or (4) patients had BCLC stage C.
6. Portal vein involvement (Chen's groups A and B, or Cheng's type I-III) 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; Chen's group B or Cheng's type III,
involvement of the main portal vein.
7. Hepatic vein invasion (VV1 to VV2) were allowed. Patients with tumor thrombus in
inferior vena cava (VV3 type, Sakamoto type 1) can be included; However, patients
with inferior vena cava tumor thrombus exceeding the diaphragmatic plane (Sakamoto
type II) and reaching the right atrium (Sakamoto type III) cannot be included in the
study;
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 ×10^9/L; (3) Platelet count ≥50
×10^9/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.
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: superior mesenteric vein (Cheng's
type IV), or with inferior vena cava tumor thrombus exceeding the diaphragmatic
plane (Sakamoto type II) or reaching the right atrium (Sakamoto type III) cannot be
included in the study.
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
Zip:
362000
Country:
China
Status:
Recruiting
Contact:
Last name:
Yan-jun Wang, M.D.
Phone:
+15872415556
Email:
wangyanjun@fjmu.edu.cn
Facility:
Name:
TongjiHospital
Address:
City:
Wuhan
Zip:
430000
Country:
China
Status:
Recruiting
Contact:
Last name:
Ze-yang Ding, M.D.
Phone:
13407156200
Email:
dingzyang@sina.com
Investigator:
Last name:
Jianping Zhao, M.D.
Email:
Sub-Investigator
Investigator:
Last name:
Xin Luo, M.D.
Email:
Sub-Investigator
Start date:
May 19, 2020
Completion date:
December 30, 2024
Lead sponsor:
Agency:
Wan-Guang Zhang
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:
Haplox Biotechnology Co., Ltd.
Agency class:
Industry
Collaborator:
Agency:
Geneplus-Beijing Co. Ltd.
Agency class:
Industry
Collaborator:
Agency:
The Second Affiliated Hospital of Fujian Medical University
Agency class:
Other
Source:
Tongji Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05713994
