Hepatocellular Carcinoma Non-ResectableEarly Phase 1NCT07746960
Chemotherapy With the Ralox Regimen Combined With Anlotinib and Penpulimab for Unresectable Hepatocellular Carcinoma
A Early Phase 1 study testing Intravenous chemotherapy with the Ralox regimen combined with Anlotinib and Penpulimab in people with Hepatocellular Carcinoma Non-Resectable, run by Nanfang Hospital, Southern Medical University at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma Non-Resectable
- What is being tested?
- Intravenous chemotherapy with the Ralox regimen combined with Anlotinib and Penpulimab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteChina
- Study dates
- 1 Jan 2025to 31 Dec 2027
- Phase
- Early Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
China1 site
Nanfang Hospital, Southern Medical University
Guangzhou, Guangdong, 510515
About this study
Official title: A Single-center Exploratory Clinical Study of 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.
Read more
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
- Being tested
- Intravenous chemotherapy with the Ralox regimen combined with Anlotinib and Penpulimab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intravenous chemotherapy with the Ralox regimen combined with Anlotinib and PenpulimabDrug
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
| Study group | Role | What they receive |
|---|---|---|
| Group of patients with unresectable hepatocellular carcinoma | Experimental | Not described Receives: Drug: Intravenous chemotherapy with the Ralox regimen combined with Anlotinib and Penpulimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
ORR
ORR = (Number of CR cases + Number of PR cases) / Total number of cases
Measured: 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
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.
Measured: 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
DCR = (Number of CR cases + Number of PR cases + Number of SD cases) / Total number of cases
Measured: through study completion.Continuously follow up the patient's subsequent treatment and survival status，an average of 1 year
Incidence of adverse events
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.
Measured: During anti - tumor treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2026
- Study start1 Jan 2025
- Primary completion31 Oct 2026 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Hepatocellular Carcinoma Non-ResectableStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nanfang Hospital, Southern Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07746960
- Sponsor's protocol ID
- NFEC-2025-009
- Status last verified
- Jul 2026
- First submitted
- 20 Jul 2026
- Last updated
- 5 Aug 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 37879230Zang 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.
PubMed 40567389Lyu 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.
PubMed 29471013Qin 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.
PubMed 25223462Hou 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.
PubMed 31306800de 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.
PubMed 31862245Bray 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.
PubMed 38572751