Donafenib Combine With Sintilimab and HAIC in Neoadjuvant of Resectable Hepatocellular Carcinoma

Overview

The investigators design a phase IIB clinical study to explore the efficacy and safety of Donafenib combined with Sintilimab and HAIC in neoadjuvant of resectable Hepatocellular Carcinoma.

Detailed description

This trial is a single-arm, non-randomized and single-center clinical study of Donafenib combined with Sintilimab and HAIC in Neoadjuvant of Resectable Hepatocellular CarcinomaIt will estimate that 30 patients who met the study criteria will be enrolled in Tianjin Medical University Cancer Institute and Hospital and neoadjuvant in Donafenib combined with Sintilimab and HAIC. The investigators will follow up and collect subjects' data monthly to evaluate the efficacy and safety of treatment.

Interventions

• Drug Donafenib
  200 mg BID,oral administration will start before the first HAIC treatment .
• Drug Sintilimab
  200 mg Q3W,Intravenous infusion will perform before HAIC treatment.
• Other HAIC
  HAIC,Q3W. The total number of HAIC treatments was determined by the investigator based on patient needs. Dose: Oxaliplatin 85 mg / m2 for 2h, Calcium folinate 400 mg / m2 for 2h, 5-FU 400 mg / m2 for 10min, followed by 5-FU 1200 mg / m2 for 23 hours).

Primary outcome measures

• MPR(Major Pathological Response) [Time frame: 1 year]

Secondary outcome measures (5)

• ORR(Objective Response Rate) [Time frame: 1 year]
• DCR(Disease Control Rate) [Time frame: 3 year]
• RFS(Recurrence-free Survival) [Time frame: 1 year]
• OS(Overall Survival) [Time frame: 3 year]
• pCR(Pathological Complete Response) [Time frame: 1 year]

Eligibility criteria

Inclusion criteria

• Voluntarily join the study and sign the informed consent;
• Age 18 \~ 80 years old (including 80 years old), male and female;
• Patients with hepatohcellular carcinoma diagnosed clinically or confirmed by histology / cytology according to the code for diagnosis and treatment of primary liver cancer (2022 Edition);
• Hepatocellular carcinoma and technically resectable (CNLC stage Ⅱb to Ⅲa), estimated residual liver volume >30%, in patients with cirrhosis, the residual liver volume is >40%. And meets at least one of the following conditions:

• The tumor is adjacent to large blood vessels or other organs, resulting in an expected surgical margin of less than 1cm;
• Cancer thrombus formation was associated with ipsilateral portal vein or hepatic vein, but the tumor thrombus did not accumulate in the main contralateral portal vein, contralateral portal vein, contralateral hepatic vein, and superior mesenteric vein;
• At least one assessable lesion (mRECIST criteria),and did not receive radiotherapy or local treatmen;
• ECOG 0 \~ 1;
• Major organs are functioning normally. Hemoglobin ≥ 90 g / L; ANC ≥ 1.5 × 109/L； Platelet count ≥ 100 × 109/L； Albumin ≥ 28 g / L; Total bilirubin ≤ 3 × ULN; AST, ALT ≤ 5 × ULN； TSH ≤ ULN； INR or PT ≤ 1.5 × ULN, APTT ≤ ULN.
• If HBsAg (+) and/or anti-HCV (+), antiviral therapy should be standard based on HBV DNA or HCV RNA test results;
• Be able to cooperate to observe adverse events. -

Exclusion criteria

• Cholangiocarcinoma, mixed cell carcinoma and fibrous laminar cell carcinoma are known
• Diffuse tumor lesions
• extrahepatic metastasis
• Active malignancies other than HCC occur within 5 years or at the same time, with the exception of cured skin basal cell carcinoma, cervical carcinoma in situ and thyroid form carcinoma;
• Received radical hepatectomy, systemic anticancer therapy for liver cancer (mainly including systemic chemotherapy, molecular targeted therapy, CTLA-4, PD-1/PD-L1 monoclonal antibody immunotherapy) and local liver therapy, including TACE, HAIC, TAE, local ablation, radiotherapy, etc;
• The following conditions were present during the course of the study: myocardial infarction, severe unstable angina pectoris, NYHA2 or higher cardiac insufficiency, poor arrhythmia control, symptomatic congestive heart failure, cerebrovascular accident;
• A history of hypertensive crisis or hypertensive encephalopathy;
• The subject has any history of active autoimmune disease or autoimmune disease (but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, pituitaritis, vasculitis, nephritis, hyperthyroidism, hypothyroidism; Subjects with vitiligo or childhood asthma are in complete remission and can be included as adults without any intervention; Asthma requiring medical intervention with bronchodilators will not be included);
• Subjects are receiving immunosuppressive, systemic or absorbable local hormone therapy for immunosuppressive purposes and continue to receive such therapy during the 2 weeks prior to enrollment;
• Abnormal coagulation (INR > 1.5 or APTT > 1.5 x ULN) with bleeding tendency or receiving thrombolysis or anticoagulation therapy;
• Known severe adverse reactions to Donafenib, sindillizumab, or severe allergic reactions to other monoclonal antibodies;
• The subject has a known history of psychotropic, alcohol, or drug abuse. -

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

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT06512467 · E20240499

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗