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

NCT07746960 | Active Not Recruiting Early Phase 1

• 1 other identifier: NFEC-2025-009
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Hepatocellular Carcinoma Non-Resectable

Outcome Measures

Primary Outcomes (1)

• ORR

  ORR = (Number of CR cases + Number of PR cases) / Total number of cases

  through study completion.Continuously follow up the patient's subsequent treatment and survival status，an average of 1 year

Secondary Outcomes (3)

• 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.

• DCR

  through study completion.Continuously follow up the patient's subsequent treatment and survival status，an average of 1 year

• Incidence of adverse events

  During anti - tumor treatment

Study Arms (1)

Group of patients with unresectable hepatocellular carcinoma

EXPERIMENTAL

Drug: Intravenous chemotherapy with the Ralox regimen combined with Anlotinib and Penpulimab

Interventions

Intravenous chemotherapy with the Ralox regimen combined with Anlotinib and Penpulimab DRUG

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

Group of patients with unresectable hepatocellular carcinoma

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Nanfang Hospital, Southern Medical University: lead

Study Sites (1)

Nanfang Hospital, Southern Medical University

Guangzhou, Guangdong, 510515, China

Location

Related Publications (7)

• Zang M, Hu X, Yuan G, Li R, Li W, Pang H, Li Q, Chen J. Tyrosine kinase inhibitors, immune checkpoint inhibitors combined with hepatic arterial infusion of oxaliplatin and raltitrexed versus oxaliplatin, 5-fluorouracil and leucovorin for intermediate and advanced hepatocellular carcinoma: A retrospective study. Int Immunopharmacol. 2023 Dec;125(Pt A):111019. doi: 10.1016/j.intimp.2023.111019. Epub 2023 Oct 24.

  PMID: 37879230 BACKGROUND

• Zang M, Li Q, Hu X, Pang H, Li R, Li W, Chen Y, Zhu P, Su K, Yuan G, Li Y, Li Y, Chen J. Camrelizumab Combined with Lenvatinib and RALOX-Hepatic Arterial Infusion Chemotherapy for Unresectable Hepatocellular Carcinoma (Cal Era): A Prospective, Single-Arm, Phase II Trial. Liver Cancer. 2025 May 26;14(6):731-742. doi: 10.1159/000546575. eCollection 2025 Dec.

  PMID: 40567389 BACKGROUND

• Lyu N, Kong Y, Mu L, Lin Y, Li J, Liu Y, Zhang Z, Zheng L, Deng H, Li S, Xie Q, Guo R, Shi M, Xu L, Cai X, Wu P, Zhao M. Hepatic arterial infusion of oxaliplatin plus fluorouracil/leucovorin vs. sorafenib for advanced hepatocellular carcinoma. J Hepatol. 2018 Jul;69(1):60-69. doi: 10.1016/j.jhep.2018.02.008. Epub 2018 Feb 20.

  PMID: 29471013 BACKGROUND

• Qin S, Cheng Y, Liang J, Shen L, Bai Y, Li J, Fan J, Liang L, Zhang Y, Wu G, Rau KM, Yang TS, Jian Z, Liang H, Sun Y. Efficacy and safety of the FOLFOX4 regimen versus doxorubicin in Chinese patients with advanced hepatocellular carcinoma: a subgroup analysis of the EACH study. Oncologist. 2014 Nov;19(11):1169-78. doi: 10.1634/theoncologist.2014-0190. Epub 2014 Sep 15.

  PMID: 25223462 BACKGROUND

• Hou JL, Zhao W, Lee C, Hann HW, Peng CY, Tanwandee T, Morozov V, Klinker H, Sollano JD, Streinu-Cercel A, Cheinquer H, Xie Q, Wang YM, Wei L, Jia JD, Gong G, Han KH, Cao W, Cheng M, Tang X, Tan D, Ren H, Duan Z, Tang H, Gao Z, Chen S, Lin S, Sheng J, Chen C, Shang J, Han T, Ji Y, Niu J, Sun J, Chen Y, Cooney EL, Lim SG. Outcomes of Long-term Treatment of Chronic HBV Infection With Entecavir or Other Agents From a Randomized Trial in 24 Countries. Clin Gastroenterol Hepatol. 2020 Feb;18(2):457-467.e21. doi: 10.1016/j.cgh.2019.07.010. Epub 2019 Jul 12.

  PMID: 31306800 BACKGROUND

• de Martel C, Georges D, Bray F, Ferlay J, Clifford GM. Global burden of cancer attributable to infections in 2018: a worldwide incidence analysis. Lancet Glob Health. 2020 Feb;8(2):e180-e190. doi: 10.1016/S2214-109X(19)30488-7. Epub 2019 Dec 17.

  PMID: 31862245 BACKGROUND

• Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024 May-Jun;74(3):229-263. doi: 10.3322/caac.21834. Epub 2024 Apr 4.

  PMID: 38572751 BACKGROUND

MeSH Terms

Interventions

anlotinib; penpulimab

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2026
• First Posted: August 5, 2026
• Study Start: January 1, 2025
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: August 5, 2026

Record last verified: 2026-07

Locations

CN (1)