Hepatocellular Carcinoma Non-Resectable
Conditions
Brief summary
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.
Interventions
DRUGIntravenous chemotherapy with the Ralox regimen combined with Anlotinib and Penpulimab
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
Sponsors
Nanfang Hospital, Southern Medical University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ORR | through study completion.Continuously follow up the patient's subsequent treatment and survival status，an average of 1 year | ORR = (Number of CR cases + Number of PR cases) / Total number of cases |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Conduct imaging evaluation | Evaluate the efficacy of solid tumor treatment according to the criteria established by mRECIST1.1 at the 6th and 12th weeks of the patient's treatment. | Perform imaging examinations such as enhanced CT/MRI of the upper abdomen and plain CT of the chest. Complete response (CR): All the arterial-phase enhanced imaging of target lesions disappears; Partial response (PR): The sum of the maximum diameters of target lesions (with enhanced arterial-phase imaging) is reduced by more than 30% compared with the baseline; Stable disease (SD): Between PR and progressive disease (PD); Progressive disease (PD): The sum of the maximum diameters of target lesions (with enhanced arterial-phase imaging) increases by more than 20% or new lesions appear. |
| DCR | through study completion.Continuously follow up the patient's subsequent treatment and survival status，an average of 1 year | DCR = (Number of CR cases + Number of PR cases + Number of SD cases) / Total number of cases |
| Incidence of adverse events | During anti - tumor treatment | Inc ofidence adverse events = Number of cases with adverse events (AE) / Total number of cases Evaluate the adverse drug reactions and grade them according to the relevant standards in the Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0), which is an internationally recognized standard. These adverse reactions include but are not limited to common ones during drug use, such as fever (body temperature \> 38 °C), leukopenia (persistent peripheral white blood cell count \< 4.0×10⁹/L), hand - foot syndrome (a combination of skin swelling, peeling, blistering, cracking, bleeding or erythema on the palms and soles, often accompanied by pain), gastrointestinal reactions (including nausea and vomiting), hair loss, etc. |
Countries
China
Outcome results
None listed