Hepatic Artery Infusion Chemotherapy for Unresectable Hepatocelluar Carcinoma Who Failed to Systemic Therapy

NCT04994236 | Unknown Phase 2

• 1 other identifier: 2LHAIC
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

Brief Summary

There are limited treatment options for patients with unresectable hepatocellular carcinoma (HCC) who failed to the combination therapy with targeted agents plus anti-PD-1/PD-L1. Hepatic artery infusion chemotherapy (HAIC) had shown potent antitumor effects in single-centered studies when was used as first-line therapy. However, HAIC was not used as second or third-line therapy.

Conditions

Hepatocellular Carcinoma

Keywords

Hepatic artery infusion chemotherapy

Outcome Measures

Primary Outcomes (1)

• Objective response of intrahepatic lesions

  Subjects with complete response or partial response assessed by RECIST v1.1 criteria.

  up to 1 year

Secondary Outcomes (6)

• duration of response of intrahepatic lesions

  up to 1 year

• Progression free survival

  up to 1 year

• Overall survival

  up to 2 year

• Treatment cycles of HAIC

  up to 1 year

• Ratio of R0 resection

  up to 1 year

Study Arms (1)

Hepatic Artery Infusion Chemotherapy

EXPERIMENTAL

Subjects assigned to this arm will receive chemotherapy via catheterizations placed into the hepatic artery.

Drug: Hepatic artery infusion chemotherapy with FOLFOX regimens (oxaliplatin, fluorouracil, and leucovorin)

Interventions

Hepatic artery infusion chemotherapy with FOLFOX regimens (oxaliplatin, fluorouracil, and leucovorin) DRUG

The FOLFOX regiments were given via hepatic artery catheterization, including oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, fluorouracil bolus 400 mg/m2, followed by fluorouracil infusion 2400 mg/m2 for 46 hours. If no severe adverse events occurred, the treatment will be repeated every 3 weeks.

Also known as: HAIC

Hepatic Artery Infusion Chemotherapy

Eligibility Criteria

• Age: 18 Years - 90 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Hepatocellular carcinoma diagnosed histologically/cytologically, or meeting the clinical diagnostic criteria of the "Guidelines for the Diagnosis and Treatment of Hepatocellular Carcinoma (2019 Edition)."
• Unresectable or advanced hepatocellular carcinoma that was assessed by the investigator. Advanced hepatocellular carcinoma was defined as BCLC C stage or Chinese Liver Cancer stage (CNLC) IIIa or IIIb stage.
• Had at least one measurable lesion in the liver.
• Liver function Child-Pugh classification of A or B7.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Patients who have received combination therapy with targeted agents combined with immune checkpoint inhibitors and have developed intolerable adverse effects or imaging confirmed intrahepatic tumor progression and have signed an informed consent form. Targeted agents include sorafenib, lenvatinib, donafenib, regorafenib, apatinib, bevacizumab (or biosimilar), and anlotinib; immune checkpoint inhibitors (mainly PD-1/PD-L1 antibodies) include pembrolizumab, nivolumab, camrelizumab, sintilimab, toripalimab, atezolizumab, and tislelizumab. Additional eligible subjects: subjects who have received at least one HAIC treatment were entered into safety evaluation (SAS); subjects who have received at least one imaging evaluation after treatment were entered into effectiveness evaluation (ITT).
• Adequate bone marrow and organ function. Reassessment of bone marrow and organ function as described above is required prior to each HAIC treatment.
• Leukocytes ≥ 3 x 10\^9/L within the last 14 days.
• Platelets ≥ 50×10\^9/L in the last 14 days without transfusion.
• hemoglobin ≥ 90 g/L in the last 14 days without blood transfusion or erythropoietin administration.
• total bilirubin ≤ 2 x the upper limit of normal (ULN)
• albumin ≥ 30 g/L in the absence of human albumin or plasma transfusion within the last 14 days
• AST and ALT ≤ 3 x ULN.
• serum creatinine at ≤1.5×ULN.
• International Normalized Ratio (INR) of prothrombin time ≤ 1.5×ULN.

You may not qualify if:

• Pathologic diagnosed with mixed liver cancer, fibrous lamellar cell carcinoma or other non-hepatocellular malignancy component.
• Previous or concurrent other malignancies, except adequately treated non-melanotic skin cancer, carcinoma in situ of the cervix, and papillary thyroid cancer
• History of organ transplantation or hepatic encephalopathy.
• Hypersensitivity to iodine-containing contrast agents, oxaliplatin, calcium folinic acid, and fluorouracil.
• History of gastrointestinal perforation and/or fistula within 6 months, history of intestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), extensive bowel resection (partial colectomy or extensive small bowel resection complicated by chronic diarrhea), Crohn's disease, ulcerative colitis, or long-term chronic diarrhea.
• Uncontrollable hypertension, systolic blood pressure \> 140 mmHg or diastolic blood pressure \> 90 mmHg after optimal medical therapy, history of hypertensive crisis or hypertensive encephalopathy.
• Gastrointestinal bleeding due to portal hypertension within 6 months; G3 varices by gastrointestinal endoscopy within 3 months.
• Subjects requesting withdrawal of informed consent.
• Other circumstances that the investigator deems inappropriate for participation in the clinical trial.

Sponsors & Collaborators

• Hui-Chuan Sun: lead

Study Sites (1)

Zhongshan Hospital

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

Related Publications (3)

• He MK, Liang RB, Zhao Y, Xu YJ, Chen HW, Zhou YM, Lai ZC, Xu L, Wei W, Zhang YJ, Chen MS, Guo RP, Li QJ, Shi M. Lenvatinib, toripalimab, plus hepatic arterial infusion chemotherapy versus lenvatinib alone for advanced hepatocellular carcinoma. Ther Adv Med Oncol. 2021 Mar 25;13:17588359211002720. doi: 10.1177/17588359211002720. eCollection 2021.

  PMID: 33854567 BACKGROUND

• Zhou J, Sun H, Wang Z, Cong W, Wang J, Zeng M, Zhou W, Bie P, Liu L, Wen T, Han G, Wang M, Liu R, Lu L, Ren Z, Chen M, Zeng Z, Liang P, Liang C, Chen M, Yan F, Wang W, Ji Y, Yun J, Cai D, Chen Y, Cheng W, Cheng S, Dai C, Guo W, Hua B, Huang X, Jia W, Li Y, Li Y, Liang J, Liu T, Lv G, Mao Y, Peng T, Ren W, Shi H, Shi G, Tao K, Wang W, Wang X, Wang Z, Xiang B, Xing B, Xu J, Yang J, Yang J, Yang Y, Yang Y, Ye S, Yin Z, Zhang B, Zhang B, Zhang L, Zhang S, Zhang T, Zhao Y, Zheng H, Zhu J, Zhu K, Liu R, Shi Y, Xiao Y, Dai Z, Teng G, Cai J, Wang W, Cai X, Li Q, Shen F, Qin S, Dong J, Fan J. Guidelines for the Diagnosis and Treatment of Hepatocellular Carcinoma (2019 Edition). Liver Cancer. 2020 Dec;9(6):682-720. doi: 10.1159/000509424. Epub 2020 Nov 11.

  PMID: 33442540 BACKGROUND

• Finn RS, Ikeda M, Zhu AX, Sung MW, Baron AD, Kudo M, Okusaka T, Kobayashi M, Kumada H, Kaneko S, Pracht M, Mamontov K, Meyer T, Kubota T, Dutcus CE, Saito K, Siegel AB, Dubrovsky L, Mody K, Llovet JM. Phase Ib Study of Lenvatinib Plus Pembrolizumab in Patients With Unresectable Hepatocellular Carcinoma. J Clin Oncol. 2020 Sep 10;38(26):2960-2970. doi: 10.1200/JCO.20.00808. Epub 2020 Jul 27.

  PMID: 32716739 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Oxaliplatin; Fluorouracil; Leucovorin

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)

Coordination Complexes; Organic Chemicals; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Study Officials

• Hui-Chuan Sun, MD&PhD

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hui-Chuan Sun, MD&PhD

CONTACT

+86-21-64037181; sun.huichuan@zs-hospital.sh.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Surgery

Study Record Dates

• First Submitted: July 29, 2021
• First Posted: August 6, 2021
• Study Start: July 1, 2021
• Primary Completion: August 31, 2022
• Study Completion: December 31, 2022
• Last Updated: August 13, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)