Sintilimab Plus Bevacizumab and SIRT for Intermediate-advanced HCC

Official title

Sintilimab, Bevacizumab Plus Y-90 Selective Internal Radiation Therapy for Patients With Unresectable Intermediate-advanced Hepatocellular Carcinoma: a Prospective, Single-center, Single Arm Trial

Overview

This study is conducted to evaluate the efficacy and safety of sintilimab, bevacizumab plus Y-90 selective internal radiation therapy (SIRT) for patients with unresectable intermediate-advanced hepatocellular carcinoma (HCC).

Detailed description

This is a single-center, prospective study to evaluate the efficacy and safety of sintilimab, bevacizumab plus SIRT (Sin-Bev-SIRT) in patient with unresectable HCC.

23 patients with unresectable intermediate-advanced HCC (BCLC B/C stage) will be enrolled in this study. The patients will receive sintilimab (200mg I.V. Q3W) and bevacizumab (7.5mg/kg I.V. Q3W) at 3-7 days after SIRT. 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.

The primary end point of this study is Progression free survival (PFS) per mRECIST. The secondary endpoints are PFS per RECIST 1.1, objective response rate (ORR), disease control rate (DCR), overall survival (OS) and adverse events (AEs).

Interventions

• Drug Sin-Bev-SIRT
  Sintilimab 200mg I.V. q3w and bevacizumab 7.5mg/kg I.V. q3w will be started at 3-7 days after the first SIRT. Treatment of sintilimab and bevacizumab will last up to 24 months. Patients will be allowed to have sintilimab or bevacizumab as a sigle agent and will be still considered on study when the other drug cause intolerable toxicity.

Primary outcome measures

• Progression free survival (PFS) according to mRECIST [Time frame: 3 years]

Secondary outcome measures (5)

• Progression free survival (PFS) according to RECIST 1.1 [Time frame: 3 years]
• Objective response rate (ORR) [Time frame: 3 years]
• Disease control rate (DCR) [Time frame: 3 years]
• Overall survival (OS) [Time frame: 3 years]
• Adverse Events (AEs) [Time frame: 3 years]

Eligibility criteria

Inclusion criteria

• Unresectable HCC (BCLC stage B/C or CNLC II/III) with diagnosis confirmed by histology/cytology or clinically
• At least one measurable untreated lesion
• Intrahepatic tumors can be treated with 1-2 sessions of SIRT
• Child-Pugh score 5-7
• Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1
• Life expectancy of at least 3 months
• Patients with active hepatitis B are allowed, but they need to receive antiviral treatment to achieve a HBV DNA<10\^3 IU/mL
• Patients with hepatitis C need to finish the anti-HCV treatment

Exclusion criteria

• tumor extent ≥70% liver occupation
• Tumor thrombus involving main portal vein or both the first left and right branches of portal vein
• Vena cava invasion
• Central nervous system metastasis
• Metastatic disease that involves major airways or blood vessels
• Patients who previously received hepatic arterial infusion chemotherapy (HAIC), transarterial chemoembolization (TACE), transarterial embolization (TAE), radiotherapy, systemic therapy for HCC
• History of organ and cell transplantation
• Prior esophageal and/or gastric varices bleeding
• Hepatic dysfunction, such as ascites, esophagogastric varices, hepatic encephalopathy
• Evidence of portal hypertension with high risk of bleeding
• Use of immunosuppressive medications within 4 weeks prior to the first dose of study treatment
• Major surgical procedure or unhealed wound, ulcer, or fracture within 4 weeks prior to the first dose of study treatment
• Any life-threatening bleeding event within the previous 3 months, including the need for blood transfusion, surgical or localized treatment, or ongoing drug therapy
• Peripheral blood white blood cell count <3×10\^9/L and platelet count <50×10\^9/L
• Prolonged prothrombin time >4 seconds
• Severe organ (heart, lung, kidney) dysfunction
• History of other malignancies
• Co-infection with hepatitis B and C viruses
• Human immunodeficiency virus infection
• Pregnant or lactating patients

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• the Second Affiliated Hospital of Guangzhou Medical University — Guangzhou

Identifiers

NCT: NCT06397222 · MIIR-16

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗