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

NCT06512467 | Not Yet Recruiting Phase 2

• 1 other identifier: E20240499
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Hepatocellular Carcinoma

Keywords

Hepatocellular Carcinoma; Donafenib; Sintilimab; HAIC

Outcome Measures

Primary Outcomes (1)

• MPR(Major Pathological Response)

  After neoadjuvant therapy, the proportion of residual tumor cells was less than 30%.

  1 year

Secondary Outcomes (5)

• ORR(Objective Response Rate)

  1 year

• DCR(Disease Control Rate)

  3 year

• RFS(Recurrence-free Survival)

  1 year

• OS(Overall Survival)

  3 year

• pCR(Pathological Complete Response)

  1 year

Study Arms (1)

Donafenib combined with Sintilimab and HAIC

EXPERIMENTAL

Donafenib:200mg bid; Sintilimab:200mg Q3D; HAIC:Q3W.

Drug: Donafenib; Drug: Sintilimab; Other: HAIC

Interventions

Donafenib DRUG

200 mg BID,oral administration will start before the first HAIC treatment .

Donafenib combined with Sintilimab and HAIC

Sintilimab DRUG

200 mg Q3W,Intravenous infusion will perform before HAIC treatment.

Donafenib combined with Sintilimab and HAIC

HAIC OTHER

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).

Donafenib combined with Sintilimab and HAIC

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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. -

You may not qualify if:

• 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. -

Sponsors & Collaborators

• Tianjin Medical University Cancer Institute and Hospital: lead

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

donafenib; sintilimab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Central Study Contacts

WEI ZHANG, Doctor

CONTACT

18622025401; zhangweitjch@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2024
• First Posted: July 22, 2024
• Study Start: July 30, 2024
• Primary Completion (Estimated): July 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: July 22, 2024

Record last verified: 2024-07