This study is conducted to evaluate the efficacy and safety of transarterial chemoembolization with drug-eluting beads (DEB-TACE) plus hepatic artery infusion chemotherapy (HAIC) compared with HAIC alone for unresectable large hepatocellular carcinoma (HCC).
This is a multicenter, prospective and randomized study to evaluate the efficacy and safety of DEB-TACE (with CalliSpheres) plus HAIC compared with HAIC alone for unresectable large HCC (\>7cm). 230 patients with initially unresectable large HCC (\> 7cm) will be enrolled in this study. The patients will receive either DEB-TACE plus HAIC (dTACE-HAIC) or HAIC as the primary treatment using an 1:1 randomization scheme. In the dTACE-HAIC arm, the microcatheter will be reserved at the proper/left/right hepatic artery and chemotherapy drugs (FOLFOX-based regimen) will be intra-arterially administered though the microcatheter. The treatment can be repeated on demand (at a 4-6-week interval usually) based on the evaluation of follow-up laboratory and imaging examination by the multidisciplinary team. In the HAIC arm, treatment will repeated once every 3 weeks for up to six cycles. During follow-up, the potential resectability of the tumor will be assessed by the multidisciplinary team (MDT). Once the tumors become resectable, curative surgical resection will be recommended for the patients. The primary end point of this study is overall survival (OS). The secondary endpoints are tumor response (objective response rate and disease control rate), success rate of conversion to resection, progression-free survival (PFS), and adverse events (AEs).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
230
For DEB-TACE, superselective catheterization is performed and CalliSpheres loaded with pirarubicin is use for chemoembolization. The embolization end point was blood stasis of the tumor-feeding arteries. In patients with huge or bilobar multiple lesions, 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 proper/left/right hepatic artery. The FOLFOX-based regimen is intra-arterially administered. During follow-up, the treatment will be repeated on demand (at a 4-6-week interval usually) based on the evaluation of the follow-up laboratory and imaging examination.
HAIC treatment is divided into 3-week cycles. The microcatheter is advanced into the proper/left/right hepatic artery on day 1 in every cycle of treatment. After the patient returned to the ward, the FOLFOX-based regimen is intra-arterially administered though the microcatheter. The treatment is repeated once every 3 weeks for up to six cycles.
the Second Affiliated Hospital of Guangzhou Medical University
Guangzhou, Guangdong, China
RECRUITINGOverall survival (OS)
The time from date of randomization to death due to any cause.
Time frame: 4 years.
Objective response rate (ORR) per mRECIST.
The proportion of patients with the best response of complete response (CR) or partial response (PR) according to mRECIST.
Time frame: 4 years.
ORR per RECIST 1.1.
The proportion of patients with the best response of CR or PR according to RECIST 1.1.
Time frame: 4 years.
Disease control rate (DCR) per mRECIST.
The proportion of patients with the best response of CR, PR, or stable disease (SD) according to mRECIST.
Time frame: 4 years.
DCR per RECIST 1.1.
The proportion of patients with the best response of CR, PR, or SD according to RECIST 1.1.
Time frame: 4 years.
Progression free survival (PFS) per mRECIST.
The time from date of randomization until the first occurrence of disease progression (according to mRECIST) or death due to any cause, whichever occurs first.
Time frame: 4 years.
Progression free survival (PFS) per RECIST 1.1.
The time from date of randomization until the first occurrence of disease progression (according to RECIST 1.1) or death due to any cause, whichever occurs first.
Time frame: 4 years.
Success rate of conversion to resection
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CalliSpheres (100-300 µm) loaded with pirarubicin for transarterial chemombolization: Typically, one vial of the beads was loaded with 60 mg pirarubicin. If blushed tumors is still visible after the embolization with one vial of beads, regular microspheres (8spheres) with diameters of 100-700 μm are additionally injected. FOLFOX-based regimen for hepatic arterial infusion chemotherapy: oxaliplatin, 85 mg/m2 infusion for 2 hours; leucovorin, 400 mg/m2 infusion for 2 hours; and 5-FU, 400 mg/m2 bolus infusion and then 2400 mg/m2 continuous infusion over 46 h.
FOLFOX-based regimen for hepatic arterial infusion chemotherapy: oxaliplatin, 85 mg/m2 infusion for 2 hours; leucovorin, 400 mg/m2 infusion for 2 hours; and 5-FU, 400 mg/m2 bolus infusion and then 2400 mg/m2 continuous infusion over 46 h.
The proportion of patients with initially unresectable large HCC who were evaluated by the surgical team as suitable for surgical resection after dTACE-HAIC or HAIC treatment.
Time frame: 4 years.
Adverse Events (AEs)
Number of patients with AEs assessed by Common Terminology Criteria for Adverse Events v5.0.
Time frame: 4 years.