Transcatheter Arterial Chemoembolization Combined With Sintilimab and Bevacizumab for Advanced Hepatocellular Carcinoma: An Open-label, Single-arm, Single-center, Prospective Study
Overview
- Phase
- Phase 2
- Intervention
- TACE combined with sorafenib and tislelizumab
- Conditions
- Hepatocellular Carcinoma Non-resectable
- Sponsor
- Second Affiliated Hospital of Guangzhou Medical University
- Enrollment
- 30
- Locations
- 2
- Primary Endpoint
- Overall survival (OS)
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
This study will evaluate the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with sorafenib and tislelizumab in patients with advanced hepatocellullar carcinoma (HCC).
Detailed Description
This is a Phase II study to evaluate the efficacy and safety of TACE combined with sorafenib and tislelizumab in patients with advanced HCC. 30 subjects with advanced HCC (Barcelona-Clinic- Liver-Cancer \[BCLC\] stage C, or China liver cancer staging \[CNLC\] IIIa and IIIb) will be enrolled in the study. Both sorafenib (400mg P.O. Bid) and tislelizumab (200mg I.V. q3w) will be started at 3-7 days after the first TACE. TACE will be repeated if clinically indicated based on the evaluation of follow-up laboratory and imaging examination. Sorafenib will last until disease progresses, intolerable toxicity, withdrawal of informed consent, loss of follow-up, death, or other circumstances that require termination of treatment, whichever occurs first. Sorafenib administration will be delayed in cases of grade ≥2 hand-foot syndrome, grade \>3 hematologic toxicities or grade ≥3 hypertension. After recovery, sorafenib will be reintroduced at a reduced dose according the sorafenib dose delay and reduction guidelines. Treatment of tislelizumab will last up to 24 months, or until disease progresses, intolerable toxicity, withdrawal of informed consent, loss of follow-up, death, or other circumstances that require termination of treatment, whichever occurs first. Patients will be allowed to have sorafenib or tislelizumab as a sigle agent and will be still considered on study when the other drug cause intolerable toxicity.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Advanced HCC (BCLC stage C, or CNLC IIIa and IIIb ) with diagnosis confirmed by histology/cytology or clinically
- •Disease not amenable to curative therapies but amenable to TACE
- •At least one measurable untreated lesion
- •No prior systemic therapy for HCC
- •Child-Pugh score 5-7
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrollment
- •Adequate organ and hematologic function
- •Life expectancy of at least 3 months
- •For women of childbearing potential and for men: agreement to remain abstinent
Exclusion Criteria
- •Diagnosis of fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
- •Diffuse HCC
- •Portal vein tumor thrombus (PVTT) involves the main trunk and contralateral branch or upper mesenteric vein
- •Inferior vena cava tumor thrombus
- •Metastatic disease that involves major airways or blood vessels
- •Symptomatic, untreated or progressing central nervous system metastasis
- •Uncontrolled tumor-related pain
- •Patients who received prior systemic therapy, immunotherapy, TACE, transcatheter arterial radioembolization (TARE), transcatheter arterial embolization (TAE), hepatic arterial infusion chemotherapy (HAIC) or radiation therapy for HCC
- •Treatment with systemic immunostimulatory agents
- •Use of herbal therapies or traditional Chinese medicines with anti-cancer activity within 2 weeks
Arms & Interventions
TACE-Sor-Tis
TACE combined with sorafenib and tislelizumab.
Intervention: TACE combined with sorafenib and tislelizumab
Outcomes
Primary Outcomes
Overall survival (OS)
Time Frame: 24 months
The time from initiation of treatment until the date of death from any cause.
Secondary Outcomes
- DCR assessed by investigators according to mRECIST.(24 months)
- DOR assessed by investigators according to mRECIST.(24 months)
- ORR assessed by investigators according to mRECIST.(24 months)
- Adverse Events (AEs)(24 months)
- Progression free survival (PFS) assessed by investigators according to Response Evalutaion Criteria in Solid Tumors (RECIST) v1.1 and immune-related RECIST (irRECIST).(24 months)
- Objective response rate (ORR) assessed by investigators according to RECIST 1.1 and irRECIST.(24 months)
- Disease control rate (DCR) assessed by investigators according to RECIST 1.1 and irRECIST.(24 months)
- Duration of response (DOR) assessed by investigators according to RECIST 1.1 and irRECIST.(24 months)
- PFS assessed by investigators according to Modified RECIST (mRECIST).(24 months)