Resectable Hepatocellular Carcinoma
Conditions
Keywords
peri-operative treatment, hepatocellular carcinoma
Brief summary
The purpose of this phase Ib/II multicenter randomized control study is to investigate the efficacy and safety of peri-operative treatment with combination of CTLA-4, PD-1 antibodies and bevacizumab in resectable HCC
Detailed description
This study is a prospective, national multi-center clinical trial. Patients with initially resectable hepatocellular carcinoma were randomly assigned to receive neoadjuvant therapy in three groups: IBI310+ sintilimab + bevacizumab (Group A), IBI310+ sintilimab (Group B), and Sintilimab + bevacizumab (Group C).
Interventions
DRUGIBI310+ sintilimab + bevacizumab
systemic therapy
DRUGIBI310+ sintilimab
systemic therapy
DRUGsintilimab + bevacizumab
systemic therapy
Sponsors
Shanghai Zhongshan Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Written informed consent shall be obtained prior to any trial-related procedures. 2. Male or female patients aged ≥18 years and ≤75 years. 3. Initial resectable hepatocellular carcinoma (HCC) confirmed by imaging, pathology or cytology. 4. No macrovascular tumor thrombus or extrahepatic metastasis detected on imaging examinations. 5. Single intrahepatic tumor \>5 cm in diameter, or 2-3 intrahepatic tumors with no restriction on tumor diameter (corresponding to CNLC stage Ib-IIa of primary liver cancer in China). 6. The maximum tumor diameter \< 8 cm. 7. Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1. 8. Child-Pugh Class A liver function. 9. No prior systemic therapy or locoregional therapy for HCC; patients with recurrence ≥2 years after previous curative surgical resection or ablation are eligible for enrollment. 10. At least one measurable lesion per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1). 11. Adequate organ function.
Exclusion criteria
1. Histologically or cytologically confirmed tumors containing components of fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, cholangiocarcinoma, or other mixed subtypes. 2. History of hepatic encephalopathy or prior liver transplantation. 3. Currently participating in an interventional clinical trial, or received any investigational medicinal product or investigational device within 4 weeks prior to the first study drug administration. 4. Prior receipt of any of the following therapies: anti-PD-1, anti-PD-L1, anti-PD-L2 agents, or agents targeting other T-cell co-stimulatory or co-inhibitory receptors (including but not limited to CTLA-4, OX-40, CD137). 5. Received systemic therapy with Chinese patent medicines with anti-tumor indications or immunomodulatory agents (including thymopeptides, interferons, interleukins; excluding local intrapleural administration for controlling pleural effusion) within 2 weeks prior to the first study drug administration. 6. History of active autoimmune disease requiring systemic therapy (e.g., disease-modifying agents, corticosteroids, immunosuppressants) within 2 years before the first study drug administration. Replacement therapies (e.g., thyroxine, insulin, physiologic corticosteroids for adrenal or pituitary insufficiency) shall not be regarded as systemic treatment. 7. Receiving systemic corticosteroid therapy (excluding intranasal, inhaled, or other locally administered corticosteroids) or any other form of immunosuppressive therapy within 7 days prior to the first study drug administration. Note: Physiologic doses of corticosteroids (≤10 mg prednisone equivalent per day) are permitted. 8. Known history of allogeneic solid organ transplantation (excluding corneal transplantation) or allogeneic hematopoietic stem cell transplantation. 9. Known hypersensitivity to any study drug used in this trial. 10. Have not fully recovered from toxicities and/or complications induced by any prior intervention before study treatment initiation. 11. Known history of human immunodeficiency virus (HIV) infection. 12. Untreated active hepatitis B virus (HBV) infection. 13. Subjects with active hepatitis C virus (HCV) infection. 14. Received any live vaccine within 30 days prior to the first study drug administration (Day 1 of Cycle 1). 15. Pregnant or lactating women. 16. Presence of any severe or uncontrolled systemic disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average depth of pathological response | 6 months | Pathological response depth is defined as the proportion of non-viable tumors in surgical specimens to the total sample after neoadjuvant therapy. The average pathological response depth is defined as the average value of the pathological response depth. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 1y-RFS rate | 12 months | The proportion of patients without disease recurrence or death within 1 year following the second randomization |
| 1y-EFS rate | 12 months | The proportion of patients without disease progression precluding surgical resection, post-operative disease recurrence, or death within 1 year after the first randomization |
Contacts
CONTACTHuichuan Sun, MD, PHD
Outcome results
None listed