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

NCT05166239 | Completed Phase 2 DMC

• 1 other identifier: HAIC-Cola
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Hepatocellular Carcinoma; Portal Vein Thrombosis

Keywords

Hepatocellular Carcinoma; Portal Vein Thrombosis

Outcome Measures

Primary Outcomes (1)

• 6-month progression-free survival rate

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

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

Secondary Outcomes (5)

• Overall survival

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

• Objective survival rate

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

• Progression-free survival

  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.

• Time to progression

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

• Number of patients with treatment-related adverse events

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

Study Arms (2)

HAIC-Cola group

EXPERIMENTAL

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. 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.

Procedure: HAIC; Drug: Lenvatinib 1; Drug: PD-1 Inhibitors

Cola group

ACTIVE COMPARATOR

12/8 mg (weight ≥ 60kg / \< 60 kg) of Lenvatinib once daily. PD-1 inhibitors injection intravenously or percutaneously every 4 week.

Drug: Lenvatinib 2; Drug: PD-1 inhibitors 2

Interventions

PD-1 inhibitors 2 DRUG

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

Cola group

HAIC PROCEDURE

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.

HAIC-Cola group

Lenvatinib 1 DRUG

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

HAIC-Cola group

PD-1 Inhibitors DRUG

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

Also known as: PD-1

HAIC-Cola group

Lenvatinib 2 DRUG

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

Cola group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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;

You may not qualify if:

• 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.
• 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..

Sponsors & Collaborators

• Peking University: lead

Study Sites (1)

Peking Univerisity Cancer Hospital

Beijing, Beijing Municipality, 100142, China

Location

Related Publications (22)

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

  PMID: 30970190 BACKGROUND

• 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.

  PMID: 22353262 BACKGROUND

• 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.

  PMID: 30943423 BACKGROUND

• 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.

  PMID: 18650514 BACKGROUND

• 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.

  PMID: 19095497 BACKGROUND

• 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.

  PMID: 29433850 BACKGROUND

• 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.

  PMID: 27806234 BACKGROUND

• 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.

  PMID: 27234522 BACKGROUND

• 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.

  PMID: 25689070 BACKGROUND

• 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.

  PMID: 31790344 BACKGROUND

• 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.

  PMID: 30515783 BACKGROUND

• 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.

  PMID: 30811474 BACKGROUND

• 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.

  PMID: 30922731 BACKGROUND

• 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.

  PMID: 30213452 BACKGROUND

• 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.

  PMID: 31420358 BACKGROUND

• Nie J, Wang C, Liu Y, Yang Q, Mei Q, Dong L, Li X, Liu J, Ku W, Zhang Y, Chen M, An X, Shi L, Brock MV, Bai J, Han W. Addition of Low-Dose Decitabine to Anti-PD-1 Antibody Camrelizumab in Relapsed/Refractory Classical Hodgkin Lymphoma. J Clin Oncol. 2019 Jun 10;37(17):1479-1489. doi: 10.1200/JCO.18.02151. Epub 2019 Apr 30.

  PMID: 31039052 BACKGROUND

• Xu J, Zhang Y, Jia R, Yue C, Chang L, Liu R, Zhang G, Zhao C, Zhang Y, Chen C, Wang Y, Yi X, Hu Z, Zou J, Wang Q. Anti-PD-1 Antibody SHR-1210 Combined with Apatinib for Advanced Hepatocellular Carcinoma, Gastric, or Esophagogastric Junction Cancer: An Open-label, Dose Escalation and Expansion Study. Clin Cancer Res. 2019 Jan 15;25(2):515-523. doi: 10.1158/1078-0432.CCR-18-2484. Epub 2018 Oct 22.

  PMID: 30348638 BACKGROUND

• Zhu H, Yang X, Zhao Y, Yi C. Efficacy of anti-PD-1 antibody SHR-1210 as second-line treatment in hepatocellular carcinoma patient with sorafenib resistance: A case report. Medicine (Baltimore). 2019 May;98(20):e15755. doi: 10.1097/MD.0000000000015755.

  PMID: 31096541 BACKGROUND

• Zhang Z, Zhou Y, Hu K, Li Z, Wang Z, Huang Y. Complete response of early stage hepatocellular carcinoma in a patient treated with combination therapy of camrelizumab (SHR-1210) and apatinib. Dig Liver Dis. 2019 Oct;51(10):1488-1490. doi: 10.1016/j.dld.2019.07.005. Epub 2019 Aug 7. No abstract available.

  PMID: 31401020 BACKGROUND

• Gao Q, Wang XY, Qiu SJ, Yamato I, Sho M, Nakajima Y, Zhou J, Li BZ, Shi YH, Xiao YS, Xu Y, Fan J. Overexpression of PD-L1 significantly associates with tumor aggressiveness and postoperative recurrence in human hepatocellular carcinoma. Clin Cancer Res. 2009 Feb 1;15(3):971-9. doi: 10.1158/1078-0432.CCR-08-1608.

  PMID: 19188168 BACKGROUND

• El-Khoueiry AB, Sangro B, Yau T, Crocenzi TS, Kudo M, Hsu C, Kim TY, Choo SP, Trojan J, Welling TH Rd, Meyer T, Kang YK, Yeo W, Chopra A, Anderson J, Dela Cruz C, Lang L, Neely J, Tang H, Dastani HB, Melero I. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet. 2017 Jun 24;389(10088):2492-2502. doi: 10.1016/S0140-6736(17)31046-2. Epub 2017 Apr 20.

  PMID: 28434648 BACKGROUND

• Hodi FS, Ballinger M, Lyons B, Soria JC, Nishino M, Tabernero J, Powles T, Smith D, Hoos A, McKenna C, Beyer U, Rhee I, Fine G, Winslow N, Chen DS, Wolchok JD. Immune-Modified Response Evaluation Criteria In Solid Tumors (imRECIST): Refining Guidelines to Assess the Clinical Benefit of Cancer Immunotherapy. J Clin Oncol. 2018 Mar 20;36(9):850-858. doi: 10.1200/JCO.2017.75.1644. Epub 2018 Jan 17.

  PMID: 29341833 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Immune Checkpoint Inhibitors

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Study Officials

• Xiaodong Wang, MD

  Peking University Cancer Hospital & Institute

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 26, 2021
• First Posted: December 21, 2021
• Study Start: January 10, 2022
• Primary Completion: December 29, 2023
• Study Completion: December 28, 2025
• Last Updated: January 23, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)