HAIC Combined with Donafenib and Sintilimab As Perioperative Treatment for Resectable Hepatocellular Carcinoma Patients At High Risk of Recurrence

NCT06812039 | Recruiting Phase 2 DMC

• 1 other identifier: 2412311-5
• Study Type: interventional
• Target: 165
• Locations: 1 country
• Sites: 3

Brief Summary

This study will evaluate the efficacy and safety of therapy perioperative treatment with HAIC combined with donafenib and sintilimab (group A)/ donafenib combined with sintilimab (group B) compared with direct surgery (group C) in resectable HCC patients who are at high risk for disease recurrence.

Conditions

Hepato Cellular Carcinoma (HCC)

Outcome Measures

Primary Outcomes (1)

• 1-yr RFS rate

  the proportion of patients who have not experienced recurrence or death from any cause at 12 months after hepatectomy.

  24 months

Secondary Outcomes (7)

• MPR rate

  Up to approximately 12 weeks

• pCR rate

  Up to approximately 12 weeks

• ORR

  Up to approximately 12 weeks

• RFS

  Up to approximately 2 years

• PFS

  Up to approximately 2 years

Study Arms (3)

Group A

EXPERIMENTAL

HAIC combined with sintilimab and donafenib

Drug: HAIC combined with sintilimab and donafenib

Group B

EXPERIMENTAL

Sintilimab and Donafenib

Drug: Sintilimab and Donafenib

Group C

ACTIVE COMPARATOR

Direct surgery

Procedure: Surgery

Interventions

HAIC combined with sintilimab and donafenib DRUG

HAIC: Two cycles, Q3W. The chemotherapy regimen consists of oxaliplatin 85 mg/m² over 2 hours and raltitrexed 2 mg/m² over 1 hour. Donafenib: Treatment should begin the day after the completion of the first HAIC, with an initial dose of 0.1g bid p.o.. The investigator may increase the dose to 0.2g bid depending on the patient's condition. Sintilimab: Administration may begin after the first HAIC, 200 mg iv Q3W. After surgery, continued sintilimab and donafenib for 6 cycles.

Group A

Sintilimab and Donafenib DRUG

Donafenib: an initial dose of 0.1g bid p.o. The investigator may increase the dose to 0.2g bid depending on the patient's condition. Sintilimab: 200 mg iv Q3W. After surgery, continued sintilimab and donafenib for 6 cycles.

Group B

Surgery PROCEDURE

After surgery, received sintilimab and donafenib for 6 cycles.

Group C

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntary enrollment with written informed consent obtained
• Age 18 to 75 years (inclusive), regardless of gender
• Histologically or pathologically confirmed previously untreated hepatocellular carcinoma (HCC) or clinically diagnosed previously untreated HCC according to the AASLD guidelines.
• Initial resectable status as assessed by the investigator (expected to achieve R0 resection, sufficient liver remnant volume, and Child-Pugh class A, as per the "Chinese Expert Consensus on Neoadjuvant Therapy for Liver Cancer (2023 Edition)").
• At least one measurable lesion according to mRECIST criteria.
• Tumor burden meets one of the following conditions:
• A single tumor with a diameter \> 5 cm;
• Multiple tumors with the largest tumor diameter \> 3 cm, with \< 5 tumors in total;
• Presence of portal vein tumor thrombus (Vp1-Vp2).
• Liver function: Child-Pugh score of 5-6.
• ECOG 0-1
• Life expectancy of at least 3 months.
• Women of childbearing potential (defined as not postmenopausal or surgically sterilized) must have a negative serum pregnancy test within 7 days prior to the study drug administration.
• Both women and men of childbearing potential must use reliable contraception during the study and for 60 days following the last dose of the study drug.
• For HBV-infected patients: If HBV-DNA is ≥ 10⁴ copies/ml within 14 days prior to enrollment, antiviral therapy (preferably entecavir) must be initiated to reduce HBV-DNA to \< 10⁴ copies/ml before entering the study. Antiviral therapy should continue, with regular monitoring of liver function and HBV-DNA levels.

You may not qualify if:

• Patients with distant metastasis.
• Patients with portal vein tumor thrombosis (Vp3-Vp4).
• History of any other malignant tumor within the past 5 years, unless the patient has received potentially curative treatment and there is no evidence of recurrence in the past 5 years. This 5-year time requirement does not apply to patients who have successfully undergone resection for basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, cervical carcinoma in situ, or other carcinoma in situ.
• History or current presence of congenital or acquired immunodeficiency diseases.
• Active or previously documented autoimmune diseases or inflammatory disorders (including but not limited to: autoimmune hepatitis, interstitial pneumonia, inflammatory bowel disease, systemic lupus erythematosus, vasculitis, uveitis, pituitary inflammation, hyperthyroidism or hypothyroidism, asthma requiring bronchodilators for treatment, etc.). Patients with vitiligo or asthma fully resolved in childhood and not requiring intervention as adults may be included.
• History of severe psychiatric disorders.
• Conditions affecting the absorption, distribution, metabolism, or elimination of the study drugs (e.g., severe vomiting, chronic diarrhea, bowel obstruction, malabsorption, etc.).
• Major surgery within 4 weeks prior to enrollment (as defined by the investigator).
• History of allogeneic stem cell or solid organ transplantation (except for corneal transplantation).
• Received other systemic antitumor therapies (including traditional Chinese medicine with antitumor indications) within 2 weeks or 5 half-lives (whichever is longer) prior to study drug administration, or unresolved adverse events related to prior treatments that have not recovered to ≤ CTCAE Grade 1.
• Use of systemic immunosuppressive drugs within 2 weeks prior to enrollment, or anticipated need for systemic immunosuppressive therapy during the study.
• Concurrent use of drugs that may prolong the QTc interval and/or induce Tdp, or drugs affecting drug metabolism.
• Known or suspected allergy to donafenib, recombinant humanized PD-1 monoclonal antibodies, or similar agents, or a history of hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins, or to excipients of the study drugs.
• Uncontrolled hepatic encephalopathy, hepatorenal syndrome, ascites, pleural effusion, or pericardial effusion.
• Active bleeding or coagulation disorders, bleeding tendencies, or ongoing treatment with thrombolytics, anticoagulants, or antiplatelet therapy.

Sponsors & Collaborators

• Fudan University: lead

Study Sites (3)

Fujian Cancer Hospital

Fuzhou, Fujian, 350014, China

NOT YET RECRUITING

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200062, China

RECRUITING

TianJin Medical University Cancer Institute & Hospital

Tianjin, Tianjin Municipality, 300000, China

NOT YET RECRUITING

MeSH Terms

Interventions

sintilimab; donafenib; Surgical Procedures, Operative

Central Study Contacts

Lu Wang, M.D.

CONTACT

86-18121299357; w.lr@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 19, 2025
• First Posted: February 6, 2025
• Study Start: January 1, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): January 31, 2028
• Last Updated: February 6, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (3)