HAIC Combined With Donafenib Tosilate and Toripalimab for Unresectable HCC

• Status: Not yet recruiting
• Trial end date: 2024-09-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a prospective, single-armed, multicentric, explorative phase II clinical research of conversional therapy with combination of hepatic arterial infusion chemotherapy(HAIC), Donafenib Tosilate and Toripalimab for unresectable hepatocellular carcinoma.

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

Details

• Lead Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
• Treatments: Fluorouracil; Leucovorin; Oxaliplatin

Criteria

Inclusion Criteria:

• Signed an informed consent form, abled to comply with visits and related procedures specified in the program;

• Age 18-75 years old (including the boundary value), male or female;

• Zubrod-ECOG-WHO scored 0 to 1;

• Expected survival time ≥ 12 weeks;

• Serum AFP detection and imaging examination meet the clinical diagnostic criteria for hepatocellular carcinoma in the "National Health Commission of the People's Republic of China. Guidelines for diagnosis and treatment of primary liver cancer in China (2019 edition)";

• Liver function grading: Child-Pugh grade A or better B grade (≤7 points);

• According to the modified solid tumor efficacy evaluation criteria (mRECIST), at least one imaging measurable lesion;

• Newly diagnosed hepatocellular carcinoma patients who have not undergone any local or systematic treatment for hepatocellular carcinoma in the past;

• Patients with hepatocellular carcinoma who have been evaluated by researchers and do not have the conditions for radical resection surgery, but are expected to achieve radical resection through translational therapy, include but are not limited to one of the following situations:

1. The tumor is massive, close to or involves the main intrahepatic ducts, and the surgical margin is expected to be 1 cm or closer to the edge of the tumor, making it difficult to achieve R0 resection;

2. The tumor is large, but limited to the target resection of the liver segment;

3. Tumors with large vascular carcinoma suppositories, such as portal vein primary branch carcinoma suppositories (not entering the main trunk), hepatic vein cancer suppositories (not entering the inferior vena cava), but portal vein cancer embolus can only be limited to one side and cannot affect the contralateral side;

4. Tumor nodules ≥ 4, and mainly concentrated on the side of the liver;

5. other conditions in which the researcher believes that radical resection may be achieved through translational therapy;

• Full organ and bone marrow function, and the laboratory test values within 7 days before enrollment meet the following requirements (no blood components, cell growth factors, albumin, and other drugs for corrective treatment are allowed within the first 14 days of obtaining laboratory tests), as follows:

1. Blood count: absolute neutrophil count (ANC) ≥ 1.5×10^9/L; Platelet count (PLT) ≥75×10^9/L; Hemoglobin content (hemoglobin, HGB) ≥80g/L;

2. Liver function: serum total bilirubin (TBIL) ≤ 1.5× upper limit of normal value (ULN); Alanine aminotransferase (ALT) and aspartate aminotransase (AST) ≤5×ULN; Serum albumin ≥ 28 g/L; alkaline phosphatase (ALP) ≤5×ULN;

3. Renal function: serum creatinine (creatinine, Cr) ≤ 1.5× ULN or clearance of creatinine (CCr) ≥ 45mL/min (Cockcroft-Gault formula); Urinalysis results show urine protein <2+;

4. Coagulation function: the international normalized ratio (INR) is ≤2, and the activated partial thromboplastin time (APTT) ≤ 1.5 times ULS;

5. Normal thyroid function, defined as thyroid-stimulating hormone (TSH) in the normal range. If the baseline TSH is outside the normal range, subjects with total T3 (or FT3) and FT4 within the normal range can also be enrolled;

6. Myocardial enzyme profile is within the normal range (if the researcher comprehensively judges that it is not clinically significant as a simple laboratory abnormality, it is also allowed to enroll);

• Female subjects of childbearing age should undergo a negative urine or serum pregnancy test within 7 days prior to receiving the first study drug administration (day 1 of the first cycle). If the results of the urine pregnancy test cannot be confirmed as negative, a blood pregnancy test is required. Women of non-reproductive age are defined as at least 1 year after menopause, or have undergone surgical sterilization or hysterectomy;

• If there is a risk of conception, all subjects (whether male or female) should use contraception with an annual failure rate of less than 1% throughout the treatment period until 120 days after the last study drug administration of treatment.

Exclusion Criteria:

• Histology contains fibroblast hepatocellular carcinoma, sarcoma-like hepatocellular carcinoma, cholangiocarcinoma and other components;

• Patients with hepatocellular carcinoma who have previously undergone radical resection and recurrent hepatic cancer;

• Have received liver transplantation in the past;

• Have previously received systemic therapy for hepatocellular carcinoma, including targeted drug therapy such as sorafenib, renvatinib, and rigofenib, or immunomodulatory agent therapy such as anti-PD-1, anti-PD-L1/L2, and anti-CTLA-4, excluding antiviral therapy; If the patient has previously used Chinese medicine with anti-tumor indications, he or she must be > 2 weeks or 5 drug half-lives (whichever is longer) after the completion of treatment and before the use of this study;

• Before starting treatment, there has not been sufficient recovery from toxicity and / or complications caused by any intervention (i.e., ≤ grade 1 or reach baseline, excluding fatigue or hair loss);

• Patients with any extrahepatic organ or lymph node metastases, including but not limited to: lung metastases, bone metastases, brain metastases or local lymph node metastases;

• There are tumors in the left and right liver lobes, such as diffuse multiple tumors of the whole liver, tumor infiltration of contralateral phylloscopic vein branches, and concomitant inferior vena cava cancer suppositories, etc. There is no potential possibility of transformable resection;

• There is difficult to control hepatic encephalopathy, hepatorenal syndrome, ascites, pleural effusion or pericardial effusion;