Hepatocellular Carcinoma Non-resectable
Conditions
Keywords
hepatocellular carcinoma, lenvatinib, transarterial chemoembolization, drug-eluting bead, hepatic arterial infusion chemotherapy, portal vein tumor thrombosis, sintilimab
Brief summary
This study is conducted to evaluate the efficacy and safety of lenvatinib plus sintilimab, transarterial chemoembolization (TACE) with drug-eluting beads (DEB-TACE) and hepatic artery infusion chemotherapy (HAIC) with FOLFOX regemen (LEN+SIN+DEB-TACE+HAIC) versus lenvatinib plus sintilimab and DEB-TACE (LEN+SIN+DEB-TACE) for large hepatocellular carcinoma (\> 7cm) with portal vein tumor thrombosis (PVTT).
Detailed description
This is a multicenter, prospective and randomized study to evaluate the efficacy and safety of LEN+SIN+DEB-TACE+HAIC compared with LEN+SIN+DEB-TACE for unresectable large HCC (\>7cm) with PVTT. 320 patients with large HCC (\> 7cm) and PVTT will be enrolled in this study. The patients will receive either Len+DEB-TACE+HAIC or Len+DEB-TACE using an 1:1 randomization scheme. In the LEN+SIN+DEB-TACE+HAIC arm, the microcatheter will be reserved at the main hepatic tumor-feeding artery after DEB-TACE and chemotherapy drugs (oxaliplatin, fluorouracil and leucovorin; FOLFOX-based regimen) will be intra-arterially administered though the microcatheter. DEB-TACE+HAIC treatments can be repeated based on the evaluation of follow-up laboratory and imaging examination by the multidisciplinary team. In the LEN+SIN+DEB-TACE arm, patients will be treated with DEB-TACE alone. TACE treatment can be repeated based on the evaluation of follow-up laboratory and imaging examination by the multidisciplinary team. In both arms, lenvatinib 12mg (body weight ≥60kg) or 8mg (body weight \<60kg) P.O. qd and sintilimab 200mg I.V. q3w will be started within 7 days after the first DEB-TACE+HAIC/DEB-TACE. The primary end point of this study is time to progression (TTP). The secondary endpoints are tumor response (objective response rate and disease control rate), overall survival (OS), and adverse events (AEs).
Interventions
COMBINATION_PRODUCTLEN+SIN+DEB-TACE+HAIC
For DEB-TACE, superselective catheterization is performed and DEBs loaded with pirarubicin is use for chemoembolization. The embolization end point was blood stasis of the tumor-feeding arteries. In order to reduce the risk of complications, the embolization end point was not achieved in the initial TACE but in the second or third TACE session. After each chemoembolization, the microcatheter is reserved at the main hepatic tumor-feeding artery. The FOLFOX-based regimen is intra-arterially administered. During follow-up, the treatment of DEB-TACE and/or HAIC will be repeated for viable tumors based on the evaluation of the follow-up laboratory and imaging examination. Lenvatinib 12mg (body weight ≥60kg) or 8mg (body weight \<60kg) P.O. qd and sintilimab 200mg I.V. q3w will be started with 7 days after the first DEB-TACE+HAIC.
COMBINATION_PRODUCTLEN+SIN+DEB-TACE
For DEB-TACE, superselective catheterization is performed and DEBs loaded with pirarubicin is use for chemoembolization. The embolization end point was blood stasis of the tumor-feeding arteries. In order to reduce the risk of complications, the embolization end point was not achieved in the initial TACE but in the second or third TACE session. During follow-up, the treatment of DEB-TACE will be repeated for viable tumors based on the evaluation of the follow-up laboratory and imaging examination. Lenvatinib 12mg (body weight ≥60kg) or 8mg (body weight \<60kg) P.O. qd and sintilimab 200mg I.V. q3w will be started with 7 days after the first DEB-TACE.
Sponsors
Second Affiliated Hospital of Guangzhou Medical University
Affiliated Hospital of Guangdong Medical University
Zhongshan People's Hospital, Guangdong, China
Huizhou Municipal Central Hospital
Jieyang People's Hospital
Guangzhou Development District Hospital
First People's Hospital of Foshan
Anqing Municipal Hospital
Jinan University Affiliated Shunde Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* a confirmed diagnosis of HCC * the largest intrahepatic lesion \>7 cm * presence of PVTT on imaging * tumor recurrence after curative treatment (hepatectomy or ablation) is eligible for enrollment * Eastern Cooperative Oncology Group performance status ≤1 * Child-Pugh class A/B * adequate hematologic and organ function, with leukocyte count\>3.0×10\^9/L, neutrophil count\>1.5×10\^9/L, platelet count≥75×10\^9/L, hemoglobin 85 g/L, alanine transaminase and aspartate transaminase≤5×upper limit of the normal, creatinine clearance rate≤1.5×upper limit of the normal; prothrombin time prolongation ≤4 seconds * life expectancy of at least 3 months
Exclusion criteria
* accompanied with vena cava tumor thrombus * central nervous system involvement * previous treatment with TACE, HAIC, TAE, radiotherapy, or systemic therapy * organ (heart and kidneys) dysfunction, unable to tolerate TACE or HAIC treatment * history of other malignancies * uncontrollable infection * history of HIV * history of organ or cells transplantation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to progression (TTP) | 4 years | The time from date of randomization until the first occurrence of disease progression (according to mRECIST). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | 4 years | The proportion of patients with the best response of complete response (CR) or partial response (PR) according to mRECIST. |
| Disease control rate (DCR) | 4 years | The proportion of patients with the best response of CR, PR, or stable disease (SD) according to mRECIST. |
| Overall survival (OS) | 5 years | The time from date of randomization to death due to any cause. |
| Adverse Events (AEs) | 4 years. | Number of patients with AEs assessed by Common Terminology Criteria for Adverse Events v5.0. |
Countries
China
Contacts
CONTACTMingyue Cai, Dr.
CONTACTKangshun Zhu, Dr.
STUDY_CHAIRKangshun Zhu, Dr.
Second Affiliated Hospital of Guangzhou Medical University
Outcome results
None listed