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Status unknownNCT05007587Updated Aug 16, 2021

Lenvatinib Plus HAIC of Modified FOLFOX Regime vs Lenvatinib Plus HAIC of ROX Regime in Patients With Advanced HCC

An Early Phase 1 interventional study of Lenvatinib and mFOLFOX regimen in Hepatocellular Carcinoma Stage IIIa, sponsored by Zhejiang Cancer Hospital. Status unknown at 1 site in China. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2021-08-16.

Sponsored by Zhejiang Cancer Hospital · Early Phase 1, Interventional, and Treatment

The sponsor has not verified this record recently (last verified Jun 2021), so the status shown — last known as Enrolling by invitation — may be out of date.
Phase
Early Phase 1
Study type
Interventional
Enrollment
60
Allocation
Randomized
Ages
18 Years to 75 Years
Sex
All
01

Study summary

Lenvatinib Plus Hepatic Arterial Infusion of Modified FOLFOX Regime vs Lenvatinib Plus Hepatic Arterial Infusion of Oxaliplatin Plus Raltitrexed in Patients with Advanced Hepatocellular Carcinoma

Read the detailed description

Hepatic arterial infusion chemotherapy is one of the important means for the treatment of advanced liver cancer. A multicenter randomized controlled study has confirmed that modified FOLFOX hepatic arterial infusion chemotherapy can significantly improve the prognosis of patients with advanced liver cancer and prolong the survival period of patients. The 2020 edition of CSCO guidelines for the diagnosis and treatment of liver cancer has recommended oxaliplatin based FOLFOX arterial infusion regimen as the first-line treatment of advanced liver cancer. FOLFOX regimen is safe and effective, but fluorouracil needs more than 46 hours of long-term infusion, patients have difficulty in moving during catheterization, and increase the risk of thrombosis, so it is urgent to find a short-term infusion of fluorouracil. As a new antimetabolic drug, raltitrexed can be used for short-term infusion, and its plasma concentration half-life is longer than that of fluorouracil. Previous studies have shown that compared with FOLFOX arterial infusion regimen, oxaliplatin combined with raltitrexed regimen has longer overall survival (OS) and progression free survival (PFS) in the treatment of advanced liver cancer. In addition, as an advanced liver cancer, lenvastinib has been recommended as a targeted drug for the first-line treatment of advanced HCC. This study intends to explore the efficacy and safety of modified FOLFOX regimen compared with oxaliplatin combined with raltitrexed (Rox regimen) in the treatment of lenvastinib combined with HAIC, so as to provide more clinical schemes for further improving the survival rate of patients with advanced liver cancer.

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Conditions studied

  • Hepatocellular Carcinoma Stage IIIa

Keywords

  • Lenvatinib
  • HAIC
  • HCC
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In context

Carcinoma

6,741 studies on the registry are indexed under Carcinoma; 1,161 are open to participants now.

This study's planned enrollment of 60 is above the median of 45 across 5,170 interventional studies indexed under Carcinoma.

Browse Carcinoma studies →

Lead sponsor

Zhejiang Cancer Hospital is the lead sponsor of 271 studies on the registry; 116 are open to participants now.

Counted across the registry records on this site, refreshed daily.

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Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Voluntary participation and informed consent, aged 18-75;
  2. Patients with HCC confirmed by histopathology or meeting the clinical diagnostic criteria in the 2019 edition of the diagnostic and therapeutic criteria for primary liver cancer;
  3. BCLC stage C patients with vascular invasion and without extrahepatic metastasis;
  4. Child Pugh liver function classification: A or B grade;
  5. ECOG physical strength score was 0-2 points;
  6. No previous systemic or local treatment, and the expected survival time is more than 3 months;
  7. According to recist1.1, the patient must have at least one measurable target lesion that has passed CT or MRI examination, and the tumor imaging evaluation was conducted within 2 weeks before receiving the study drug;
  8. Full organ and bone marrow function: WBC ≥ 3.0 × 109/L； NE≥1.5 × 109/L； PLT≥75 × 109/L； Liver and kidney function ALT and AST ≤ 5uln; TBIL≤2ULN； Albumin ≥ 28g / L; Cr≤1.5 ULN； International normalized ratio (INR) ≤ 1.5 or prothrombin time (PT) exceeding the normal control range ≤ 4 seconds;

Exclusion criteria

Exclusion Criteria:

  1. Hepatocholangiocarcinoma, mixed cell carcinoma and fibrolamellar cell carcinoma are known;
  2. Uncontrollable ascites, hepatic encephalopathy or esophageal variceal bleeding;
  3. Patients with hypertension who can not be reduced to normal range after antihypertensive drug treatment (systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg);
  4. Patients with myocardial ischemia or myocardial infarction above grade II, poorly controlled arrhythmia, myocardial ischemia or myocardial infarction above grade II, poorly controlled arrhythmia (QTc interval ≥ 450 ms) (QTc interval was calculated by fridericia formula);
  5. Patients with history of gastrointestinal bleeding or definite tendency of gastrointestinal bleeding in the past 3 months, such as esophageal varices with bleeding risk, local active ulcer lesions, fecal occult blood ≥ +, can not be included in the group;
  6. Pregnant or lactating women, patients with fertility are unwilling or unable to take effective contraceptive measures;
  7. patients with a history of HIV infection;
  8. The researcher judges other situations that may affect the clinical research and the judgment of research results;
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Study design

Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Single (Participant)
Enrollment
60 participants (estimated)

Study arms

  • Experimental
    Lenvatinib，Then HAIC of mFOLFOX regimen

    Cohort1：Participants were treated with 8mg lenvatinib (weight\<60kg) or 12mg lenvatinib (weight\>60kg) orally once daily on days 1 through 21, and HAIC regimen was performed every 3 weeks. The mFOLFOX regimen was administered via hepatic artery: oxaliplatin , 85mg/m2 , from hour 0 to 2 on day1 ; leucovorin , 400mg/m2 , from hour 2 to 3 on day 1 ; fluorouracil , 400mg/m2 , bolus at hour 3 ; and 2400mg/m2 over 46 hours on days 1 and 2.

    Drug: Lenvatinib · Drug: mFOLFOX regimen

  • Experimental
    Lenvatinib，Then HAIC of ROX regimen

    Cohort2：Participants were treated with 8mg lenvatinib (weight\<60kg) or 12mg lenvatinib (weight\>60kg) orally once daily on days 1 through 21, and HAIC regimen was performed every 3 weeks. The ROX regimen was administered via hepatic artery: oxaliplatin , 100mg/m2 , from hour 0 to 4 on day1 ;raltitrexed , 3mg/m2 , from hour 4 to 5 on day 1.

    Drug: Lenvatinib · Drug: ROX regimen

Interventions

  • DrugLenvatinib

    8mg lenvatinib (weight\<60kg) or 12mg lenvatinib (weight\>60kg) QD

    Also known as: LENVIMA

  • DrugmFOLFOX regimen

    HAIC was performed every 3 weeks. The mFOLFOX regimen was administered via hepatic artery: oxaliplatin , 85mg/m2 , from hour 0 to 2 on day1 ; leucovorin , 400mg/m2 , from hour 2 to 3 on day 1 ; fluorouracil , 400mg/m2 , bolus at hour 3 ; and 2400mg/m2 over 46 hours on days 1 and 2.3mg/m2 , from hour 4 to 5 on day 1.

    Also known as: Oxaliplatin+Leucovorin+Fluorouracil

  • DrugROX regimen

    HAIC was performed every 3 weeks. The ROX regimen was administered via hepatic artery: oxaliplatin , 100mg/m2 , from hour 0 to 4 on day1 ;raltitrexed , 3mg/m2 , from hour 4 to 5 on day 1.

    Also known as: Raltitrexed+Oxaliplatin

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What researchers measure

Primary outcomes

  1. Objective Response Rate and Disease Control Rate of the HCC Participants

    ORR and DCR are validated indicators of the short-term clinical effects of hepatocellular carcinoma

    Time frame: from admission to discharge, up to 4 weeks

Secondary outcomes

  1. Overall Survival and Progression-free Survival of the HCC Participants

    OS and PFS are validated indicators of the long-term clinical effects of hepatocellular carcinoma

    Time frame: six months and twelve months

  2. Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0

    Treatment-Related Adverse Events are important indicators of the safety for tumor treatment

    Time frame: from admission to discharge, up to 4 weeks

Other outcomes

  1. Weight and Height

    Weight and Height will be combined to report BMI in kg/m\^2

    Time frame: from admission to discharge, up to 1 week

  2. Age

    Age is divided into \>50 and ≤50

    Time frame: from admission to discharge, up to 1 week

  3. Sex

    Sex is divided into Male and Female

    Time frame: from admission to discharge, up to 1 week

  4. ECOG score

    ECOG score is divided into 0,1,2

    Time frame: from admission to discharge, up to 1 week

  5. Tumor size

    Tumor size is divided into \>10cm and ≤10cm

    Time frame: from admission to discharge, up to 1 week

  6. Tumor number

    Tumor number is divided into single and multiple

    Time frame: from admission to discharge, up to 1 week

  7. AFP

    AFP is divided into \>1000ug/L and ≤1000ug/L

    Time frame: from admission to discharge, up to 1 week

  8. Portal vein invasion

    Portal vein invasion is divided into Vp1-2, Vp3, Vp4

    Time frame: from admission to discharge, up to 1 week

  9. Extrahepatic spread

    Extrahepatic spread is divided into Yes and No

    Time frame: from admission to discharge, up to 1 week

  10. Hepatitis B infection

    Hepatitis B infection is divided into Yes and No

    Time frame: from admission to discharge, up to 1 week

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Study locations

1 site
  • The Cancer Hospital of the University of Chinese Academy of Sciences（Zhejiang Cancer Hospital）
    Hangzhou, Zhejiang 310022, China
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References and documents

Publications

  • Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12. Erratum In: CA Cancer J Clin. 2020 Jul;70(4):313. doi: 10.3322/caac.21609. PubMed 30207593 ↗
  • Global Burden of Disease Cancer Collaboration; Fitzmaurice C, Allen C, Barber RM, Barregard L, Bhutta ZA, Brenner H, Dicker DJ, Chimed-Orchir O, Dandona R, Dandona L, Fleming T, Forouzanfar MH, Hancock J, Hay RJ, Hunter-Merrill R, Huynh C, Hosgood HD, Johnson CO, Jonas JB, Khubchandani J, Kumar GA, Kutz M, Lan Q, Larson HJ, Liang X, Lim SS, Lopez AD, MacIntyre MF, Marczak L, Marquez N, Mokdad AH, Pinho C, Pourmalek F, Salomon JA, Sanabria JR, Sandar L, Sartorius B, Schwartz SM, Shackelford KA, Shibuya K, Stanaway J, Steiner C, Sun J, Takahashi K, Vollset SE, Vos T, Wagner JA, Wang H, Westerman R, Zeeb H, Zoeckler L, Abd-Allah F, Ahmed MB, Alabed S, Alam NK, Aldhahri SF, Alem G, Alemayohu MA, Ali R, Al-Raddadi R, Amare A, Amoako Y, Artaman A, Asayesh H, Atnafu N, Awasthi A, Saleem HB, Barac A, Bedi N, Bensenor I, Berhane A, Bernabe E, Betsu B, Binagwaho A, Boneya D, Campos-Nonato I, Castaneda-Orjuela C, Catala-Lopez F, Chiang P, Chibueze C, Chitheer A, Choi JY, Cowie B, Damtew S, das Neves J, Dey S, Dharmaratne S, Dhillon P, Ding E, Driscoll T, Ekwueme D, Endries AY, Farvid M, Farzadfar F, Fernandes J, Fischer F, G/Hiwot TT, Gebru A, Gopalani S, Hailu A, Horino M, Horita N, Husseini A, Huybrechts I, Inoue M, Islami F, Jakovljevic M, James S, Javanbakht M, Jee SH, Kasaeian A, Kedir MS, Khader YS, Khang YH, Kim D, Leigh J, Linn S, Lunevicius R, El Razek HMA, Malekzadeh R, Malta DC, Marcenes W, Markos D, Melaku YA, Meles KG, Mendoza W, Mengiste DT, Meretoja TJ, Miller TR, Mohammad KA, Mohammadi A, Mohammed S, Moradi-Lakeh M, Nagel G, Nand D, Le Nguyen Q, Nolte S, Ogbo FA, Oladimeji KE, Oren E, Pa M, Park EK, Pereira DM, Plass D, Qorbani M, Radfar A, Rafay A, Rahman M, Rana SM, Soreide K, Satpathy M, Sawhney M, Sepanlou SG, Shaikh MA, She J, Shiue I, Shore HR, Shrime MG, So S, Soneji S, Stathopoulou V, Stroumpoulis K, Sufiyan MB, Sykes BL, Tabares-Seisdedos R, Tadese F, Tedla BA, Tessema GA, Thakur JS, Tran BX, Ukwaja KN, Uzochukwu BSC, Vlassov VV, Weiderpass E, Wubshet Terefe M, Yebyo HG, Yimam HH, Yonemoto N, Younis MZ, Yu C, Zaidi Z, Zaki MES, Zenebe ZM, Murray CJL, Naghavi M. Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-years for 32 Cancer Groups, 1990 to 2015: A Systematic Analysis for the Global Burden of Disease Study. JAMA Oncol. 2017 Apr 1;3(4):524-548. doi: 10.1001/jamaoncol.2016.5688. Erratum In: JAMA Oncol. 2017 Mar 1;3(3):418. doi: 10.1001/jamaoncol.2017.0098. PubMed 27918777 ↗
  • 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 ↗
  • Benson AB, D'Angelica MI, Abbott DE, Abrams TA, Alberts SR, Anaya DA, Anders R, Are C, Brown D, Chang DT, Cloyd J, Covey AM, Hawkins W, Iyer R, Jacob R, Karachristos A, Kelley RK, Kim R, Palta M, Park JO, Sahai V, Schefter T, Sicklick JK, Singh G, Sohal D, Stein S, Tian GG, Vauthey JN, Venook AP, Hammond LJ, Darlow SD. Guidelines Insights: Hepatobiliary Cancers, Version 2.2019. J Natl Compr Canc Netw. 2019 Apr 1;17(4):302-310. doi: 10.6004/jnccn.2019.0019. PubMed 30959462 ↗
  • Spallanzani A, Orsi G, Andrikou K, Gelsomino F, Rimini M, Riggi L, Cascinu S. Lenvatinib as a therapy for unresectable hepatocellular carcinoma. Expert Rev Anticancer Ther. 2018 Nov;18(11):1069-1076. doi: 10.1080/14737140.2018.1524297. Epub 2018 Sep 21. PubMed 30220234 ↗
  • Song DS, Song MJ, Bae SH, Chung WJ, Jang JY, Kim YS, Lee SH, Park JY, Yim HJ, Cho SB, Park SY, Yang JM. A comparative study between sorafenib and hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis. J Gastroenterol. 2015 Apr;50(4):445-54. doi: 10.1007/s00535-014-0978-3. Epub 2014 Jul 16. PubMed 25027973 ↗
  • Obi S, Sato S, Kawai T. Current Status of Hepatic Arterial Infusion Chemotherapy. Liver Cancer. 2015 Sep;4(3):188-99. doi: 10.1159/000367746. Epub 2015 Aug 12. PubMed 26674592 ↗
  • 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. PubMed 29471013 ↗
  • Zhuang BW, Li W, Xie XH, Hu HT, Lu MD, Xie XY. Sorafenib versus hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma: a systematic review and meta-analysis. Jpn J Clin Oncol. 2019 Sep 1;49(9):845-855. doi: 10.1093/jjco/hyz069. PubMed 31063184 ↗
  • Chen S, Zhang K, Liu W, Yu W. Hepatic arterial infusion of oxaliplatin plus raltitrexed in patients with intermediate and advanced stage hepatocellular carcinoma: A phase II, single-arm, prospective study. Eur J Cancer. 2020 Jul;134:90-98. doi: 10.1016/j.ejca.2020.03.032. Epub 2020 Jun 1. PubMed 32497895 ↗
  • He M, Li Q, Zou R, Shen J, Fang W, Tan G, Zhou Y, Wu X, Xu L, Wei W, Le Y, Zhou Z, Zhao M, Guo Y, Guo R, Chen M, Shi M. Sorafenib Plus Hepatic Arterial Infusion of Oxaliplatin, Fluorouracil, and Leucovorin vs Sorafenib Alone for Hepatocellular Carcinoma With Portal Vein Invasion: A Randomized Clinical Trial. JAMA Oncol. 2019 Jul 1;5(7):953-960. doi: 10.1001/jamaoncol.2019.0250. PubMed 31070690 ↗

Individual participant data

Plan to share: No

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 16, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT05007587
Lead sponsor
Zhejiang Cancer Hospital
Collaborators
First Affiliated Hospital of Zhejiang University, First Affiliated Hospital of Wenzhou Medical University, Second Affiliated Hospital of Wenzhou Medical University, Shaoxing People's Hospital, The Third Affiliated Hospital of Wenzhou Medical University, Jinhua Central Hospital
Responsible party
Sponsor
First posted
Aug 16, 2021
Start date
Jul 1, 2021
Primary completion
Jun 30, 2022 (estimated)
Completion
Jun 30, 2023 (estimated)
Last update
Aug 16, 2021

Study contacts

Jiaping Zheng, Doctor
study chair · Zhejiang Cancer Hospital

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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