Donafenib Combine With Sintilimab and HAIC (Hepatic Artery Infusion Chemotherapy，HAIC）in the First-line Treatment of Unresectable Hepatocellular Carcinoma

• Status: Not yet recruiting
• Trial end date: 2024-12-01
• Target enrollment: 0
• Participant gender: All

Summary

The investigators design a phase IIB clinical study to explore the efficacy and safety of Donafenib combined with Sintilimab and HAIC in the first-line treatment of unresectable hepatocellular carcinoma

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Tianjin Medical University Cancer Institute and Hospital

Criteria

Inclusion Criteria:

1. Voluntarily join the study and sign the informed consent;

2. Age 18 ~ 80 years old (including 80 years old), male and female;

3. Patients with hepatohcellular carcinoma diagnosed clinically or confirmed by histology / cytology according to the code for diagnosis and treatment of primary liver cancer (2019 Edition);

4. Patients with unresectable or metastatic hepatocellular carcinoma;

5. No systematic treatment. If receiving adjuvant chemotherapy after local treatment more than 12 months, and patients with disease progression or metastasis can also be included in the group;

6. The end time of the last intervention, radiotherapy and ablation should be > 4 weeks;

7. Patients who underwent hepatectomy in the past should be R0 resection, and the tumor recurrence should be more than 24 months after operation;

8. At least one assessable lesion (RECIST 1.1 criteria);

9. Expected survival time ≥ 3 months;

10. ECOG 0 ~ 1;

11. Child Pugh ≤ 7;

12. Be able to cooperate to observe adverse events;

13. Major organs are functioning normally.

1. Hemoglobin ≥ 90 g / L;

2. ANC ≥ 1.5 × 109/L；

3. Platelet count ≥ 75 × 109/L；

4. Albumin ≥ 28 g / L;

5. Total bilirubin ≤ 2 × ULN;

6. AST, ALT ≤ 5 × ULN；

7. ALP ≤ 5 × ULN；

8. Creatinine ≤ 1.5 × ULN；

9. INR or PT ≤ 1.5 × ULN； J) APTT ≤ 1.5 × ULN。

Exclusion Criteria:

1. Fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, cholangiocarcinoma and other components confirmed by histology / cytology in the past;

2. Have a history of malignancy other than hepatocellular carcinoma unless the following criteria are met:

A) The patient has received possible curative treatment and there is no evidence of the disease within 5 years; B) Successful resection of basal cell carcinoma of skin, squamous cell carcinoma of skin, superficial bladder carcinoma, carcinoma in situ of cervix and other cancers in situ

3. Diffuse tumor lesions;

4. Tumor vascular invasion occurs in one or more of the following situations:

1. Involving superior mesenteric vein;

2. Involving inferior vena cava;

5. History of hepatic encephalopathy, hepatorenal syndrome, or history of liver transplantation;

6. Pleural effusion, ascites and pericardial effusion with clinical symptoms requiring drainage;

7. Central system metastasis;

8. Previous history of severe mental illness;

9. Have a disease that affects absorption, distribution, metabolism, or clearance of the drug under study (such as severe vomiting, chronic diarrhea, intestinal obstruction, absorption disorder, etc.);

10. Previous allogeneic stem cell or parenchymal organ transplantation;

11. Previously received targeted therapy of anti VEGF and / or signal pathways such as VEGFR, RAF and MEK, such as sorafenib, renvatinib and regofinib, or immunomodulator therapy such as anti-PD-1, anti-PD-L1 and anti-CTLA-4;

12. Patients who have received other anti-tumor systemic treatment in the past, including traditional Chinese medicine with anti-tumor indications less than 2 weeks before the administration of this study, or the adverse events caused by previous treatment have not recovered to ≤ CTCAE level 1; The toxicity of previous anti-tumor treatment did not include grade 1 / 2 neurotoxicity and hair loss caused by oxaliplatin;

13. Taking drugs that may prolong QTc and / or induce tip twist transition ventricular tachycardia (TDP) or drugs that affect metabolism at the same time;

14. Previous or current congenital or acquired immunodeficiency disease;

15. Active or previously documented autoimmune disease or inflammatory disease.

16. Previous allogeneic stem cell or parenchymal organ transplantation;

17. Systemic immunosuppressive drugs were used within 2 weeks before enrollment, or systemic immunosuppressive drugs expect to be needed during the study, except for the following:

d) Intranasal, inhalation, topical or local injection (such as intra-articular injection) of corticosteroids; e) Systemic corticosteroids with dose not exceeding 10 mg / day, prednisone or other effects; f) Prophylactic use of corticosteroids for hypersensitivity;

18. Allergy to Donafenib or similar drugs, or history of hypersensitivity to chimeric or humanized antibodies or fusion proteins, or allergy to the excipients of the study drugs;

19. Have active bleeding or abnormal coagulation function, have bleeding tendency or are receiving thrombolytic, anticoagulant or antiplatelet therapy;

20. Thrombosis or thromboembolism events occurred in the past 6 months, such as stroke and / or transient ischemic attack, deep vein thrombosis, pulmonary embolism, etc;

21. Bleeding events of esophageal or gastric varices caused by portal hypertension in the past 6 months, or any life-threatening bleeding events in 3 months;

22. Cardiovascular diseases with significant clinical significance, including but not limited to acute myocardial infarction, severe / unstable angina or coronary artery bypass grafting in the past 6 months, congestive heart failure (NYHA grade > 2), arrhythmias poorly controlled or requiring pacemaker treatment, and hypertension not controlled by drugs (systolic blood pressure ≥ 140 mmHg and / or diastolic blood pressure ≥ 90 mmHg);

23. Other significant clinical and laboratory abnormalities considered by the investigator to affect safety;

24. Severe infections in the active stage or under clinical control; Active infections include:

1. HIV1/2 is positive.

2. HBsAg positive or HBV DNA > 2000iu/ml and abnormal liver function;

3. HCV antibody positive or HCV RNA ≥ 103 copies/ml and abnormal liver function;

4. Active tuberculosis;

5. Other uncontrollable active infections (CTCAE V5.0 > grade 2);

25. Not recovered from the operation, such as unhealed incision or serious postoperative complications;

26. Pregnant or lactating women, and women or men with fertility are unwilling or unable to take effective contraceptive measures.