A Trial of Cadonilimab Plus Regorafenib in Patients With Hepatocellular Carcinoma Who Failed Camrelizumab Combined With Apatinib

Official title

A Single-arm, Multicenter, Phase II Trial of Cadonilimab Plus Regorafenib in Patients With Hepatocellular Carcinoma Who Progressed on Camrelizumab Combined With Apatinib

Overview

To evaluate the efficacy and safety of cadonilimab combined with Regorafenib in patients with hepatocellular carcinoma who failed camrelizumab plus apatinib.

Interventions

• Drug Cadonilimab+regorafenib
  cadonilimab: 6mg/kg iv D1 Q2W; regorafenib: 80mg QD oral; Eligible patients will receive cadonilimab combined with regorafenib, until disease progression or intolerable toxicity or death or withdrawal of informed consent, whichever occurred first

Primary outcome measures

• objective response rate (ORR) per RECIST1.1 [Time frame: Up to two years]

Secondary outcome measures (4)

• Progression-free survival（PFS） [Time frame: Up to two years]
• Overall survival（OS） [Time frame: Up to three years]
• Duration of response (DOR) [Time frame: Up to two years]
• Occurence of AE and SAE [Time frame: Up to two years]

Eligibility criteria

Inclusion criteria

• Sign a written informed consent form before enrollment;
• Age >18 years old, both sex;
• Histological or pathological confirmed intermediate or advanced hepatocellular carcinoma, or patients with cirrhosis who meet the clinical diagnostic criteria for hepatocellular carcinoma of the American Association for the Study of Liver Diseases (AASLD);
• Have progressed on the combination treatment of camrelizumab and apatinib for HCC
• Child-Pugh Class A;
• ECOG PS score: 0\~1;
• At least 1 measurable lesion (RECIST1.1)
• Expected survival period≥12 weeks
• The function of vital organs meets the following requirements (excluding the use of any blood components and cell growth factors within 14 days):

1\. Blood routine: Neutrophils≥1.5×109/L Platelet count ≥75×109/L Hemoglobin ≥ 90g/L; 2. Liver and kidney function: Serum creatinine (SCr) ≤ 1.5 times the upper limit of normal (ULN) or creatinine clearance ≥ 50 ml/min (Cockcroft-Gault formula); Total bilirubin (TBIL) ≤ 3 times the upper limit of normal (ULN); Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level ≤ 10 times the upper limit of normal (ULN); urine protein < 2+; if urine protein ≥ 2+, 24-hour urine protein quantification shows that the protein must be ≤ 1g; 10. Normal coagulation function, no active bleeding or thrombosis disease

• International normalized ratio INR≤1.5×ULN;
• Partial thromboplastin time APTT≤1.5×ULN;
• Prothrombin time PT≤1.5×ULN; 11. Non-surgical sterilization or female patients of childbearing age 12. Subjects voluntarily join this study, have good compliance, and cooperate with safety and survival follow-up

Main Exclusion Criteria:

• Containing components such as fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, and cholangiocarcinoma that have been previously confirmed by histology/cytology;
• Have a history of hepatic encephalopathy;
• Have a history of liver transplantation;
• There is clinically significant pericardial effusion, and there are clinical symptoms of pleural effusion that require drainage;
• Clinically apparent ascites is defined as meeting the following criteria: ascites can be detected by physical examination during screening or ascites needs to be drained during screening;
• Simultaneous infection with HBV and HCV (having a history of HCV infection but negative HCV RNA can be considered as not being infected with HCV);
• Presence of central nervous system metastasis or meningeal metastasis
• Bleeding from esophageal or gastric varices caused by portal hypertension has occurred within 6 months before the first dose
• Patients with any bleeding or bleeding event ≥CTCAE grade 3 within 4 weeks before the first dose
• Arterial and venous thromboembolic events occurred within 6 months before the first dose
• Uncontrolled high blood pressure
• Symptomatic congestive heart failure
• Severe bleeding tendency or coagulation disorder
• Have a history of gastrointestinal perforation and/or fistula, intestinal obstruction within 6 months before the first dose
• Active autoimmune disease or a history of autoimmune disease
• Patients with HIV
• According to the investigator's judgment, patients with other serious concomitant diseases that endanger the patient's safety or affect the patient's completion of the study.

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

• Mengchao Hepatobiliary Hospital, Fujian Medical University — Fuzhou

Identifiers

NCT: NCT06280105 · 2023_148_01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗