Chemotherapy With the Ralox Regimen Combined With Anlotinib and Penpulimab for Unresectable Hepatocellular Carcinoma

The objective of this clinical trial study is to determine whether intravenous chemotherapy with the Ralox regimen in combination with Anlotinib and Penpulimab has certain efficacy and high safety for patients with unresectable hepatocellular carcinoma. Overall design: This clinical study is a single - center, single - arm, prospective clinical study. In this single - arm study, randomization grouping is not involved. Sample size estimation: According to previous research reports, the objective response rate (ORR0) of targeted immunotherapy for literature unresectable HCC is 30%. If α = 0.05 and 1 - β = 0.80 are set, and assuming that the ORR1 of systemic chemotherapy combined with targeted immunotherapy for unresectable HCC is 59.2%, at least 21 patients need to be enrolled as calculated by the PASS15.0 software. Considering a 10% dropout rate, 24 patients need to be enrolled. It is planned to enroll a total of 30 patients. Subjects will receive systemic intravenous chemotherapy combined with immune checkpoint inhibitors and targeted drug therapy: The intravenous chemotherapy regimen is as follows: Oxaliplatin 100 mg/m², intravenous infusion for 3 hours on Day 1, once every 3 weeks; Raltitrexed 3 mg/m², intravenous infusion for 15 minutes on Day 1. Penpulimab 200 mg, once every 3 weeks. Anlotinib 12 mg, taken orally once a day, with 2 weeks of administration followed by 1 week of discontinuation. Each cycle is 21 days. The combined medication will be continued for 3 cycles, or until obvious disease progression, patient intolerance, or until the researcher deems it necessary to stop the medication (whichever occurs first). After that, subsequent treatment will be carried out according to the clinical diagnosis and treatment routine based on the tumor situation. For each subject, safety assessment and research compliance assessment will be conducted at the first dose and at Weeks 1, 2, and 3 of treatment, and the researcher will medication provide guidance. An examination will be conducted once at the screening visit, every 6 weeks during the treatment phase, and at each research visit during the follow - up period. Throughout the entire research process, its toxicity and safety will be monitored.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

* Adult males or females;
* Meeting the relevant criteria in the "Guidelines for the Diagnosis and Treatment of Primary Liver Cancer (2022 Edition)", and diagnosed with HCC through examinations such as ultrasound, enhanced CT and, magnetic resonance imaging, liver puncture biopsy;
* Patients with unresectable HCC (patients with recurrence after radical resection are eligible for enrollment);
* ECOG PS score ≤ 2;
* Liver function of Child-Pugh class A/B, and liver function reserve ICG ≤ 30%;
* According to the mRECIST criteria for tumor assessment, having ≥ 1 measurable intrahepatic target lesion, and the estimated survival period ≥ 6 months;
* Normal organ and bone marrow functions before randomization, including: hemoglobin ≥ 90 g/L, absolute neutrophil count ≥ 1.0 × 10\^9/L, platelet count ≥ 75 × 10\^9/L, total bilirubin ≤ 2.0 × the upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 × ULN, albumin ≥ 28 g/L, international normalized ratio PT-INR ≤ 1.6, glomerular filtration rate (DCK-EPI formula) ≥ 50 mL/min, urine protein \< 2+ or 24 - hour urine protein quantification \< 1.0 g;
* Those who voluntarily sign the informed consent form.

Exclusion Criteria:

* Patients with obvious abnormalities in organ and bone marrow functions that are difficult to reverse before randomization, including: hemoglobin \< 90 g/L, absolute neutrophil count \< 1.0 × 10\^9/L, platelet count \< 75 × 10\^9/L, total bilirubin \> 2.0 × the upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \> 5 × ULN, albumin \< 28 g/L, international normalized ratio PT - INR \> 1.6, glomerular filtration rate (CKD - EPI formula) \< 30 mL/min, urine protein ≥ 2+ or 24 - hour urine protein quantification ≥ 1.0 g.
* Patients with infection, bleeding tendency, massive ascites and hepatic encephalopathy.
* Patients who have been using hepatotoxic drugs for a long - term due to their own diseases and cannot stop taking the drugs.
* Patients who have previously received chemotherapy, radiotherapy, immunotherapy or targeted therapy.
* Patients with other severe diseases of the heart, brain, kidneys and other organs, autoimmune diseases, or diseases such as HIV/tuberculosis that the researcher deems inappropriate for enrollment.
* Patients who fail to complete the treatment cycle before tumor assessment after the first treatment.
* Patients with incomplete clinical general data or imaging data.
* Patients who are currently participating in other therapeutic studies.

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