TACE-HAIC Combined With TKIs and Immunotherapy Versus TACE Alone for Hepatocellular Carcinoma With PVTT

Sponsor

Yunfei Yuan (Other)

Overall Status

Completed

CT.gov ID

NCT05535998

Collaborator

(none)

743

Enrollment

Location

17.9

Actual Duration (Months)

41.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Hepatocellular carcinoma (HCC) is characterized with vascular invasion, particularly of the portal vein, resulting in portal vein tumor thrombus (PVTT) in 10%-40% of HCC patients at the time of HCC diagnosis. The prognosis of these patients is extremely poor.Treatment efficacy and safety using a combined therapy (TACE-HAIC combined with TKIs and PD-1 inhibitors) were compared with TACE alone in treatment of HCC patients with PVTT.

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma	Procedure: TACE-HAIC Procedure: TACE Drug: Targeted therapy Drug: PD-1 inhibitors

Study Design

Study Type:

Observational

Actual Enrollment :

743 participants

Observational Model:

Cohort

Time Perspective:

Retrospective

Official Title:

TACE-HAIC Combined With Targeted Therapy and Immunotherapy Versus TACE Alone for Hepatocellular Carcinoma With Portal Vein Tumor Thrombus: A Propensity Score Matching Study

Actual Study Start Date :

Jan 1, 2021

Actual Primary Completion Date :

Sep 30, 2021

Actual Study Completion Date :

Jun 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Combined therapy group (TACE-HAIC combined with TKIs and PD-1 inhibitors) Patients recieve combined with TKIs and PD-1 inhibitors	Procedure: TACE-HAIC The TACE-HAIC which was performed using 30 mg/m2 of epirubicin mixed with 2-5 mL lipiodol, followed by pure lipiodol. Then, a catheter was placed and fixed in the tumor feeding artery for the FOLFOX-based chemotherapy infusion at the following dosage: 85 mg/m2 of oxaliplatin infusion for 2 hours; leucovorin, 400 mg/m2 infusion for 2 hours; 400 mg/m2 of 5-FU bolus; and 2400 mg/m2 of continuous 5-FU infusion for 46 hours or 1200mg/m2 of continuous 5-FU infusion for 23 hours, respectively. Repeated TACE-HAIC was performed at intervals of 3-4 weeks. Drug: Targeted therapy The TKI therapy used in this study were lenvatinib (12 mg/d for bodyweight ⩾ 60 kg or 8 mg/d for bodyweight <60 kg), sorafenib (400 mg twice a day) or apatinib (250-500 mg orally once daily). Administration of lenvatinib, apatinib or sorafenib was started on the first post-TACE day, and continually administered until disease progression developed or serious treatment-related toxicity occurred. Drug: PD-1 inhibitors PD-1 inhibitors were intravenously administered on the first post-TACE day as follows: camrelizumab 200 mg or sintilimab 200 mg or toripalimab 240 mg or tislelizumab 200 mg, every 3-4 weeks.
TACE alone group TACE alone	Procedure: TACE TACE was performed using 30 mg/m2 of epirubicin, 200 mg/m2 of carboplatin, and 4mg/m2 of MMC, mixed with 2-5 mL lipiodol. Up to 20 mL of additional pure lipiodol were injected into the tumor-feeding artery until stasis of blood flow was observed in the target artery. Repeated TACE was performed at intervals of 3-4 weeks.

Arm

Intervention/Treatment

Combined therapy group (TACE-HAIC combined with TKIs and PD-1 inhibitors)

Patients recieve combined with TKIs and PD-1 inhibitors

Procedure: TACE-HAIC

The TACE-HAIC which was performed using 30 mg/m2 of epirubicin mixed with 2-5 mL lipiodol, followed by pure lipiodol. Then, a catheter was placed and fixed in the tumor feeding artery for the FOLFOX-based chemotherapy infusion at the following dosage: 85 mg/m2 of oxaliplatin infusion for 2 hours; leucovorin, 400 mg/m2 infusion for 2 hours; 400 mg/m2 of 5-FU bolus; and 2400 mg/m2 of continuous 5-FU infusion for 46 hours or 1200mg/m2 of continuous 5-FU infusion for 23 hours, respectively. Repeated TACE-HAIC was performed at intervals of 3-4 weeks.

Drug: Targeted therapy

The TKI therapy used in this study were lenvatinib (12 mg/d for bodyweight ⩾ 60 kg or 8 mg/d for bodyweight <60 kg), sorafenib (400 mg twice a day) or apatinib (250-500 mg orally once daily). Administration of lenvatinib, apatinib or sorafenib was started on the first post-TACE day, and continually administered until disease progression developed or serious treatment-related toxicity occurred.

Drug: PD-1 inhibitors

PD-1 inhibitors were intravenously administered on the first post-TACE day as follows: camrelizumab 200 mg or sintilimab 200 mg or toripalimab 240 mg or tislelizumab 200 mg, every 3-4 weeks.

TACE alone group

TACE alone

Procedure: TACE

TACE was performed using 30 mg/m2 of epirubicin, 200 mg/m2 of carboplatin, and 4mg/m2 of MMC, mixed with 2-5 mL lipiodol. Up to 20 mL of additional pure lipiodol were injected into the tumor-feeding artery until stasis of blood flow was observed in the target artery. Repeated TACE was performed at intervals of 3-4 weeks.

Outcome Measures

Primary Outcome Measures

Tumor Response [24 months]
The tumor responses were evaluated by measuring the longest diameter of target lesions according to response evaluation criteria in solid tumors (RECIST) version 1.1
Overall survival [24 months]
Overall survival (OS) was measured from the initiation of transarterial therapy to the date of death or the last follow-up.
Progression-free survival [24 months]
Progression-free survival (PFS) was measured from the initiation of transarterial therapy to the time of progression or recurrence or last follow-up.

Secondary Outcome Measures

Conversion rate [24 rates]
Rate of patients underwent hepatic surgery after careful evaluation when an estimated residual liver volume >30-40% could be remained after R0 surgery by 2 experienced surgeons

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

(a) HCC patients with PVTT (Vp1-4) treated by TACE, or the combination therapy (TACE-HAIC combined with TKIs or an PD-1 inhibitors) as initial treatment; (b) age between 18 and 75 years; (c) Child-Pugh A or B liver function; (d) Eastern Cooperative Oncology Group (ECOG) performance status 0-1; (e) adequate hematologic blood counts (white blood cell count >3ⅹ109/L, absolute neutrophil count >1.5ⅹ109/L, platelet count

10ⅹ109/L, hemoglobin concentration >85 g/L); (f) no extrahepatic metastasis.

Exclusion Criteria:

(a) severe underlying cardiac, pulmonary, or renal diseases; (b) history of a second primary malignant tumor; (c) incomplete medical data; (d) loss to follow-up.