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Hepatocellular CarcinomaPhase 2NCT05166239

HAIC Combine With Lenvatinib and PD-1 Inhibitors for Advanced HCC With PVTT

A Phase 2 study testing HAIC, Lenvatinib 1 and PD-1 Inhibitors in people with Hepatocellular Carcinoma and Portal Vein Thrombosis, run by Peking University at 1 site in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The purpose of this study is to evaluate the safety and efficacy of hepatic arterial infusion chemotherapy combined with Lenvatinib and PD-1 inhibitors compared to Lenvatinib plus PD-1 inhibitors for advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). Read more about this study

Who is it for?
Ages 18 to 80 years
What is being tested?
HAIC, Lenvatinib 1 and PD-1 Inhibitors
Could I receive a placebo?
No, everyone receives an active treatment
How many people
66 participants
Where
1 siteChina
Study dates
10 Jan 2022to 28 Dec 2025
Phase
Phase 2
Are there results?
None posted in the registry

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 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age and gender: >18 years old and≤75 years old, both men and women.
  • All subjects must have advanced hepatocellular carcinoma with portal vein tumor thrombosis confirmed by pathological or clinical diagnosis.
  • One measurable lesion at least.
  • ECOG PS 0-1 before 1 week of treatment begnining.
  • Child-Pugh class A; ALBI class 1-2.
  • Systemic-cheomtherapy-naive and HAIC-naive.
Show all 20Show fewer
  • BCLC C stage with PVTT (Vp1 - Vp4).
  • Without distant metastasis.
  • Patients who are expected to live more than 3 months.
  • Subjects must volunteer to participate in the study, signed informed consent, and were able to comply with the program requirements of visits and related procedures.
  • Patients with laboratory values that meet the following criteria:
  • Hemoglobin≥90 g/L;
  • Neutrophile granulocytes≥1.5×109/L;
  • Platelet count≥75×109/L;
  • Albumin≥30 g/L;
  • Total serum bilirubin ≤ 2 times upper limits of normal;
  • AST and ALT ≤ 5 times upper limits of normal;
  • Serum creatinine ≤ 1.5 times upper limits of normal;
  • Alkaline phosphatase ≤ 5 times upper limits of normal;
  • Prothrombin time or international normalized ratio ≤ 1.5 times upper limits of normal, activated partial thromboplastin time (APTT) ≤ 1.5×ULN.

Who cannot join

  • Fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, cholangiocarcinoma confirmed by histology or cytology.
  • History of malignant tumor, excluding the following cases:
  • Allergic to contrast agent.
  • Allergic to oxaliplatin.
  • History of usage of immune inhibitor drug within 14 days before the injection of PD-1 inhibitors, except nasal spray and inhaled corticosteroids or physiological doses of systemic steroid hormones (no more than 10 mg/day of prednisolone or other corticosteroids with equivalent physiological doses).
  • Factors influenced oral Lenvatinib, such as inability to swallow, chronic diarrhea and intestinal obstruction, or other conditions that significantly affect the administration and absorption of the drug.
Show all 25Show fewer
  • Allergic to Lenvatinib, PD-1 inhibitors, and other mono-colonal antibodies.
  • Vaccination with live attenuated vaccine within 4 weeks before the first dose or planned during the study period.
  • Peripheral neuropathy> Grade 1.
  • History of active autoimmune disease or autoimmune disease.
  • History of other malignant tumor, except for radically treated basal cell, squamous cell skin cancer, or cervical carcinoma in situ.
  • History of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS) .
  • Clinically significant cardiovascular disease, including, but not limited to, acute myocardial infarction, severe/unstable angina or prior coronary artery bypass surgery, congestive heart failure (NYHA >2), poorly controlled arrhythmias or arrhythmias requiring pacemaker therapy, hypertension not controlled by medication (systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg) within the past 6 months.
  • Abnormal coagulation function (INR>1.5 or APTT>1.5×ULN) , have bleeding tendency, or are receiving thrombolytic therapy, anticoagulation therapy or antiplatelet therapy, etc..
  • History of inherited or acquired bleeding and thrombotic tendency, such as hemophilia, coagulopathy, thrombocytopenia, hypersplenism, etc..
  • History of significant coughing up blood 2 months before entering the study, or the daily volume of hemoptysis reached 2.5 ml or more.
  • Patients at risk of gastrointestinal bleeding, including the following:
  • There are active peptic ulcer lesions.
  • Those who have a history of melena and hematemesis within 3 months.
  • For fecal occult blood (+) or (+/-), it is necessary to recheck the stool routine within 1 week. Those who still (+) or (+/-) must undergo gastroscopy. If there is ulcer, bleeding disease, and the treating physician believes that there is a potential risk of bleeding.
  • History of thrombosis and/or embolism within 6 months of the start of treatment.
  • Complicated infections requiring drug intervention (such as intravenous infusion of antibiotics, antifungal or antiviral drugs) within 4 weeks before the first treatment, or unexplained fever >38.5°C during the screening period/before the first administration.
  • Participated in any other clinical research within 4 weeks before the first treatment.
  • History of psychotropic drug abuse or drug use.
  • Other serious physical, mental illnesses or laboratory abnormalities, which may increase the risk of participating in the research or interfere with the results of the research, and those who the researcher believes are not suitable for participating in this research.

Trial locations and contacts

1 site in 1 country.

China1 site

  • Peking Univerisity Cancer Hospital

    Beijing, Beijing Municipality, 100142

Other trials in China

About this study

Official title: Hepatic Arterial Infusion Chemotherapy Combine With Lenvatinib and PD-1 Inhibitors for Advanced Hepatocellular Carcinoma With Portal Vein Tumor Thrombosis.

The purpose of this study is to evaluate the safety and efficacy of hepatic arterial infusion chemotherapy combined with Lenvatinib and PD-1 inhibitors compared to Lenvatinib plus PD-1 inhibitors for advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT).

Read the detailed description

Hepatic arterial infusion chemotherapy (HAIC) can significantly improve the local drug concentration in liver compared to systemic chemotherapy. The efficacy of HAIC for hepatocellular (HCC), cholangiocarcinoma, gallbladder, and colorectal carcinoma liver metastasis has been proved by many published studies. HAIC with oxaliplatin and 5-fluorouracil could significantly prolong survival time for HCC patients with portal vein tumor thrombosis (PVTT). Lenvatinib, as a new oral anti-neovascularity inhibitor, was proved to have similar efficacy in HCC patients compared to sorafenib in REFLECT study. The sub-group analysis showed that the median overall survival (OS) in Lenvatinib group was significantly longer that sorafenib group in Chinese HCC patients. Recently, the programmed death-1 (PD-1) inhibitors alone or combined with targeted therapy was explored and confirmed to be effective for advanced HCC, with the median progression-free survival (PFS) and median OS of 2.1-5.6 months and 14.4-22.1 months, resepectively. Thus, the investigators carried out this prospective controlled trial to compare the efficacy and safety of HAIC combined with Lenvatinib and PD-1 inhibitors and Lenvatinib and PD-1 inhibitors for advanced HCC with PVTT.

Total 66 subjects will be recruited in this trial, each group of 33 subjects in treatment group (HAIC-Cola group) and control group (Cola group). The primary endpoint is six-month progression-free survival rate, and the secondary endpoints are OS, overall response rate (ORR), PFS, time-to-progression (TTP) and safety. The safety evaluation will be carried out according to the standard of adverse reaction classification (Common Terminology Criteria for Adverse Events, CTCAE v5.0).

Being tested
HAIC, Lenvatinib 1, PD-1 Inhibitors, Lenvatinib 2, PD-1 inhibitors 2
Keywords
Hepatocellular Carcinoma, Portal Vein Thrombosis
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • HAICProcedure or surgery

    Hepatic arterial chemotherapy consisted of infusions of oxaliplatin (35 mg/m2 for 2 hours), followed by 5-fluorouracil (600 mg/m2 for 22 hours) on day1-3 every 4 weeks.

  • Lenvatinib 1Drug

    12/8 mg (weight ≥ 60kg / < 60 kg) of Lenvatinib once daily after HAIC.

  • PD-1 InhibitorsDrug

    Also called PD-1

    PD-1 inhibitors injection intravenously or percutaneously before 24h of HAIC every 4 week.

  • Lenvatinib 2Drug

    12/8 mg (weight ≥ 60kg / < 60 kg) of Lenvatinib once daily.

  • PD-1 inhibitors 2Drug

    PD-1 inhibitors injection intravenously or percutaneously every 4 week.

Study groups in NCT05166239
Study groupRoleWhat they receive
HAIC-Cola groupExperimentalHepatic arterial chemotherapy consisted of infusions of oxaliplatin (35 mg/m2 for 2 hours), followed by 5-fluorouracil (600 mg/m2 for 22 hours) on day1-3 every 4 weeks. 12/8 mg (weight ≥ 60kg / < 60 kg) of Lenvatinib once daily after HAIC. PD-1 inhibitors injection intravenously or percutaneously before 24h of HAIC every 4 week.
Receives: Procedure: HAIC; Drug: Lenvatinib 1; Drug: PD-1 Inhibitors
Cola groupActive comparator12/8 mg (weight ≥ 60kg / < 60 kg) of Lenvatinib once daily. PD-1 inhibitors injection intravenously or percutaneously every 4 week.
Receives: Drug: Lenvatinib 2; Drug: PD-1 inhibitors 2

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 6-month progression-free survival rate

    Proportion of patients with 6- month progression-free survival after treatment begining in all patients.

    Measured: From the date of treatment begining to the date of 6 months after the treatment begining.

Secondary outcomes (5)

  1. Overall survival

    The time from treatment initiation to death due to any cause

    Measured: From date of treatment beginning until the date of death from any cause, assessed up to 100 months.

  2. Objective survival rate

    The proportion of participants in the analysis population who have complete response (CR) or partial response (PR) determined by investigators using mRECIST criteria at any time during the study.

    Measured: Evaluation of tumor burden based on mRECIST criteria through study completion, an average of once per 3 months.

  3. Progression-free survival

    The time from treatment initiation to the first documented disease progression or death due to any cause, whichever occurs firstly.

    Measured: From date of treatment beginning until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months.

  4. Time to progression

    Time to progression is defined as time from treatment initiation to radiological progression.

    Measured: Evaluation of tumor burden based on mRECIST criteria until first documented progress, assessed up to 100 months.

  5. Number of patients with treatment-related adverse events

    Number of patients with AE, treatment-related AE (TRAE), serious adverse event (SAE) assessed by CTCAE v5.0.

    Measured: Through study completion, an average of once per 1 month.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Dec 2021
  2. Study start10 Jan 2022
  3. Primary completion29 Dec 2023
  4. Study completion28 Dec 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
66 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05166239
Sponsor's protocol ID
HAIC-Cola
Status last verified
Jan 2026
First submitted
26 Nov 2021
Last updated
23 Jan 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Villanueva A. Hepatocellular Carcinoma. N Engl J Med. 2019 Apr 11;380(15):1450-1462. doi: 10.1056/NEJMra1713263. No abstract available.

    PubMed 30970190

  • Forner A, Llovet JM, Bruix J. Hepatocellular carcinoma. Lancet. 2012 Mar 31;379(9822):1245-55. doi: 10.1016/S0140-6736(11)61347-0. Epub 2012 Feb 20.

    PubMed 22353262

  • Llovet JM, Montal R, Villanueva A. Randomized trials and endpoints in advanced HCC: Role of PFS as a surrogate of survival. J Hepatol. 2019 Jun;70(6):1262-1277. doi: 10.1016/j.jhep.2019.01.028. Epub 2019 Mar 31.

    PubMed 30943423

  • Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Haussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J; SHARP Investigators Study Group. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008 Jul 24;359(4):378-90. doi: 10.1056/NEJMoa0708857.

    PubMed 18650514

  • Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, Feng J, Ye S, Yang TS, Xu J, Sun Y, Liang H, Liu J, Wang J, Tak WY, Pan H, Burock K, Zou J, Voliotis D, Guan Z. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009 Jan;10(1):25-34. doi: 10.1016/S1470-2045(08)70285-7. Epub 2008 Dec 16.

    PubMed 19095497

  • Kudo M, Finn RS, Qin S, Han KH, Ikeda K, Piscaglia F, Baron A, Park JW, Han G, Jassem J, Blanc JF, Vogel A, Komov D, Evans TRJ, Lopez C, Dutcus C, Guo M, Saito K, Kraljevic S, Tamai T, Ren M, Cheng AL. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018 Mar 24;391(10126):1163-1173. doi: 10.1016/S0140-6736(18)30207-1.

    PubMed 29433850

  • Boussiotis VA. Molecular and Biochemical Aspects of the PD-1 Checkpoint Pathway. N Engl J Med. 2016 Nov 3;375(18):1767-1778. doi: 10.1056/NEJMra1514296. No abstract available.

    PubMed 27806234

  • Ma W, Gilligan BM, Yuan J, Li T. Current status and perspectives in translational biomarker research for PD-1/PD-L1 immune checkpoint blockade therapy. J Hematol Oncol. 2016 May 27;9(1):47. doi: 10.1186/s13045-016-0277-y.

    PubMed 27234522

  • Jia Y, Zeng Z, Li Y, Li Z, Jin L, Zhang Z, Wang L, Wang FS. Impaired function of CD4+ T follicular helper (Tfh) cells associated with hepatocellular carcinoma progression. PLoS One. 2015 Feb 17;10(2):e0117458. doi: 10.1371/journal.pone.0117458. eCollection 2015.

    PubMed 25689070

  • Finn RS, Ryoo BY, Merle P, Kudo M, Bouattour M, Lim HY, Breder V, Edeline J, Chao Y, Ogasawara S, Yau T, Garrido M, Chan SL, Knox J, Daniele B, Ebbinghaus SW, Chen E, Siegel AB, Zhu AX, Cheng AL; KEYNOTE-240 investigators. Pembrolizumab As Second-Line Therapy in Patients With Advanced Hepatocellular Carcinoma in KEYNOTE-240: A Randomized, Double-Blind, Phase III Trial. J Clin Oncol. 2020 Jan 20;38(3):193-202. doi: 10.1200/JCO.19.01307. Epub 2019 Dec 2.

    PubMed 31790344

  • Gunda V, Gigliotti B, Ashry T, Ndishabandi D, McCarthy M, Zhou Z, Amin S, Lee KE, Stork T, Wirth L, Freeman GJ, Alessandrini A, Parangi S. Anti-PD-1/PD-L1 therapy augments lenvatinib's efficacy by favorably altering the immune microenvironment of murine anaplastic thyroid cancer. Int J Cancer. 2019 May 1;144(9):2266-2278. doi: 10.1002/ijc.32041. Epub 2019 Jan 24.

    PubMed 30515783

  • Kato Y, Tabata K, Kimura T, Yachie-Kinoshita A, Ozawa Y, Yamada K, Ito J, Tachino S, Hori Y, Matsuki M, Matsuoka Y, Ghosh S, Kitano H, Nomoto K, Matsui J, Funahashi Y. Lenvatinib plus anti-PD-1 antibody combination treatment activates CD8+ T cells through reduction of tumor-associated macrophage and activation of the interferon pathway. PLoS One. 2019 Feb 27;14(2):e0212513. doi: 10.1371/journal.pone.0212513. eCollection 2019.

    PubMed 30811474

  • Makker V, Rasco D, Vogelzang NJ, Brose MS, Cohn AL, Mier J, Di Simone C, Hyman DM, Stepan DE, Dutcus CE, Schmidt EV, Guo M, Sachdev P, Shumaker R, Aghajanian C, Taylor M. Lenvatinib plus pembrolizumab in patients with advanced endometrial cancer: an interim analysis of a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2019 May;20(5):711-718. doi: 10.1016/S1470-2045(19)30020-8. Epub 2019 Mar 25.

    PubMed 30922731

  • Fang W, Yang Y, Ma Y, Hong S, Lin L, He X, Xiong J, Li P, Zhao H, Huang Y, Zhang Y, Chen L, Zhou N, Zhao Y, Hou X, Yang Q, Zhang L. Camrelizumab (SHR-1210) alone or in combination with gemcitabine plus cisplatin for nasopharyngeal carcinoma: results from two single-arm, phase 1 trials. Lancet Oncol. 2018 Oct;19(10):1338-1350. doi: 10.1016/S1470-2045(18)30495-9. Epub 2018 Sep 10.

    PubMed 30213452

  • Song Y, Wu J, Chen X, Lin T, Cao J, Liu Y, Zhao Y, Jin J, Huang H, Hu J, Luo J, Zhang L, Xue H, Zhang Q, Wang W, Chen C, Feng J, Zhu J. A Single-Arm, Multicenter, Phase II Study of Camrelizumab in Relapsed or Refractory Classical Hodgkin Lymphoma. Clin Cancer Res. 2019 Dec 15;25(24):7363-7369. doi: 10.1158/1078-0432.CCR-19-1680. Epub 2019 Aug 16.

    PubMed 31420358

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing HAIC, Lenvatinib 1 and PD-1 Inhibitors in people with Hepatocellular Carcinoma and Portal Vein Thrombosis, run by Peking University at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

6-month progression-free survival rate (time frame: From the date of treatment begining to the date of 6 months after the treatment begining.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05166239, which also lists 22 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2026.

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