Transcatheter Arterial Chemoembolization Combined With Sintilimab and Bevacizumab for Unresectable Intermediate and Advanced Hepatocellular Carcinoma: A Prospective Study
Overview
- Phase
- Phase 1
- Intervention
- TACE combined with sintilimab and bevacizumab
- Conditions
- Hepatocellular Carcinoma Non-resectable
- Sponsor
- Second Affiliated Hospital of Guangzhou Medical University
- Enrollment
- 36
- Locations
- 1
- Primary Endpoint
- Adverse Events (AEs)
- Last Updated
- 4 years ago
Overview
Brief Summary
This study is to evaluate the safety and efficacy of transcatheter arterial chemoembolization (TACE) combined with sintilimab and bevacizumab in patients with unresectable intermediate or advanced hepatocellular carcinoma (HCC).
Detailed Description
This is a Phase Ib study to evaluate the safety and efficacy of TACE combined with sintilimab and bevacizumab in patients with unresectable intermediate or advanced HCC. 36-39 subjects with unresectable intermediate or advanced HCC will be enrolled in the study. This study includes dose escalation and dose expansion stage. 6-9 subjects will be enrolled in dose escalation stage for the safety evaluation. Then, sintilimab 200mg/kg IV. every three weeks (q3w) + the select specific dose of bevacizumab 7.5mg/kg (group 1) or 15mg/kg (group2) IV q3w, expand to 36 patients (18 patients each group) for the further safety and efficacy study. Sintilimab and bevacizumab 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. And the study treatment of sintilimab and bevacizumab 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Intermediate or advanced (Barcelona Clinic Liver Cancer stage B or C) HCC 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 class 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-Sin-Bev
TACE combined with sintilimab and bevacizumab.
Intervention: TACE combined with sintilimab and bevacizumab
Outcomes
Primary Outcomes
Adverse Events (AEs)
Time Frame: 24 months
Number of patients with AE, treatment-related AE (TRAE), immune-related AE (irAE), AE of special interest (AESI), serious adverse event (SAE), assessed by NCI CTCAE v5.0.
Progression free survival (PFS) assessed by investigators according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and immune-related RECIST (irRECIST).
Time Frame: 24 months
The time from initiation of treatment until the first occurrence of disease progression or death from any cause, whichever occurs first.
Secondary Outcomes
- 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)
- ORR assessed by investigators according to mRECIST.(24 months)
- DCR assessed by investigators according to mRECIST.(24 months)
- Overall survival (OS)(24 months)
- PFS assessed by investigators according to Modified RECIST (mRECIST).(24 months)
- DOR assessed by investigators according to mRECIST.(24 months)