HAIC Combined With Donafenib Tosilate and Toripalimab for Unresectable HCC

NCT05493332 | Unknown Phase 2

• 1 other identifier: 2021-KY-128
• Study Type: interventional
• Target: 93
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a prospective, single-armed, multicentric, explorative phase II clinical research of conversional therapy with combination of hepatic arterial infusion chemotherapy(HAIC), Donafenib Tosilate and Toripalimab for unresectable hepatocellular carcinoma.

Conditions

Hepatocellular Carcinoma

Keywords

HCC

Outcome Measures

Primary Outcomes (1)

• Conversion therapy success rate

  Defined as the proportion of patients who met the resection criteria after conversion therapy and successfully underwent radical resection surgery to the total number of patients enrolled.

  through study completion, an average of 2 year

Secondary Outcomes (9)

• Conversion therapy success rate based on imageological examination

  through study completion, an average of 2 year

• Objective response rate (ORR)

  through study completion, an average of 2 year

• Disease control rate(DCR）

  through study completion, an average of 2 year

• Progression-free survival（PFS）

  through study completion, an average of 2 year

• Overall survival(OS)

  through study completion, an average of 2 year

Study Arms (1)

HAIC-Donafenib-Toripalimab Group

EXPERIMENTAL

HAIC(FOLFOX)+Toripalimab+Donafenib

Procedure: HAIC(FOLFOX); Drug: Oxaliplatin; Drug: Leucovorin; Drug: Fluorouracil; Drug: Toripalimab; Drug: Donafenib

Interventions

HAIC(FOLFOX) PROCEDURE

After successful percutaneous hepatic artery cannulation, superior mesenteric arteriogram and hepatic arteriogram were performed, and after confirming that the subjects were eligible for enrollment according to the results, the hepatic artery was cannulated to the predetermined position. The catheter was connected to a syringe pump in the ward for continuous pumping of chemotherapy drugs.

Also known as: Hepatic Artery Infusion Chemotherapy, FOLFOX

HAIC-Donafenib-Toripalimab Group

Oxaliplatin DRUG

85mg/m2 IVdrip from hour 0 to 2 on D1，Q3W

HAIC-Donafenib-Toripalimab Group

Leucovorin DRUG

400mg/m2 IVdrip , from hour 0 to 2 on D1 to D2，Q3W

HAIC-Donafenib-Toripalimab Group

Fluorouracil DRUG

400mg/m2 , bolus at hour 3 ; and 600mg/m2 IVdrip over 46 hours on D1 to D2，Q3W

HAIC-Donafenib-Toripalimab Group

Toripalimab DRUG

240mg IVdrip，D3, Q3W

HAIC-Donafenib-Toripalimab Group

Donafenib DRUG

0.1g. P.O, BID, continuously

HAIC-Donafenib-Toripalimab Group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed an informed consent form, abled to comply with visits and related procedures specified in the program;
• Age 18-75 years old (including the boundary value), male or female;
• Zubrod-ECOG-WHO scored 0 to 1;
• Expected survival time ≥ 12 weeks;
• Serum AFP detection and imaging examination meet the clinical diagnostic criteria for hepatocellular carcinoma in the "National Health Commission of the People's Republic of China. Guidelines for diagnosis and treatment of primary liver cancer in China (2019 edition)";
• Liver function grading: Child-Pugh grade A or better B grade (≤7 points);
• According to the modified solid tumor efficacy evaluation criteria (mRECIST), at least one imaging measurable lesion;
• Newly diagnosed hepatocellular carcinoma patients who have not undergone any local or systematic treatment for hepatocellular carcinoma in the past;
• Patients with hepatocellular carcinoma who have been evaluated by researchers and do not have the conditions for radical resection surgery, but are expected to achieve radical resection through translational therapy, include but are not limited to one of the following situations:
• The tumor is massive, close to or involves the main intrahepatic ducts, and the surgical margin is expected to be 1 cm or closer to the edge of the tumor, making it difficult to achieve R0 resection;
• The tumor is large, but limited to the target resection of the liver segment;
• Tumors with large vascular carcinoma suppositories, such as portal vein primary branch carcinoma suppositories (not entering the main trunk), hepatic vein cancer suppositories (not entering the inferior vena cava), but portal vein cancer embolus can only be limited to one side and cannot affect the contralateral side;
• Tumor nodules ≥ 4, and mainly concentrated on the side of the liver;
• other conditions in which the researcher believes that radical resection may be achieved through translational therapy;
• Full organ and bone marrow function, and the laboratory test values within 7 days before enrollment meet the following requirements (no blood components, cell growth factors, albumin, and other drugs for corrective treatment are allowed within the first 14 days of obtaining laboratory tests), as follows:

You may not qualify if:

• Histology contains fibroblast hepatocellular carcinoma, sarcoma-like hepatocellular carcinoma, cholangiocarcinoma and other components;
• Patients with hepatocellular carcinoma who have previously undergone radical resection and recurrent hepatic cancer;
• Have received liver transplantation in the past;
• Have previously received systemic therapy for hepatocellular carcinoma, including targeted drug therapy such as sorafenib, renvatinib, and rigofenib, or immunomodulatory agent therapy such as anti-PD-1, anti-PD-L1/L2, and anti-CTLA-4, excluding antiviral therapy; If the patient has previously used Chinese medicine with anti-tumor indications, he or she must be \> 2 weeks or 5 drug half-lives (whichever is longer) after the completion of treatment and before the use of this study;
• Before starting treatment, there has not been sufficient recovery from toxicity and / or complications caused by any intervention (i.e., ≤ grade 1 or reach baseline, excluding fatigue or hair loss);
• Patients with any extrahepatic organ or lymph node metastases, including but not limited to: lung metastases, bone metastases, brain metastases or local lymph node metastases;
• There are tumors in the left and right liver lobes, such as diffuse multiple tumors of the whole liver, tumor infiltration of contralateral phylloscopic vein branches, and concomitant inferior vena cava cancer suppositories, etc. There is no potential possibility of transformable resection;
• There is difficult to control hepatic encephalopathy, hepatorenal syndrome, ascites, pleural effusion or pericardial effusion;
• Active bleeding or coagulation abnormalities, bleeding tendencies, or receiving thrombolytic, anticoagulant, or antiplatelet therapy;
• Major surgical procedures (craniotomy, thoracic or abdominal opening) or unhealed wounds, ulcers, or fractures that have not healed within 4 weeks prior to the first dose. Tissue aspiration biopsy or other minor surgical procedures within 7 days prior to the first administration, with the exception of a venipuncture catheter for the purpose of intravenous infusion;
• History of gastrointestinal bleeding within the previous 4 weeks or a clear tendency to bleed from the gastrointestinal tract (e.g., known focal active ulcer lesions, fecal occult blood++, gastroscopy if persistent fecal occult blood +), or other conditions determined by the researcher that may cause gastrointestinal bleeding (e.g., severe floor/esophageal varices);
• History of any arteriovenous thrombosis, embolism or ischemia in the previous 6 months, such as myocardial infarction, unstable angina, deep vein thrombosis, pulmonary embolism, cerebrovascular accident or transient ischemic attack;
• History of gastrointestinal perforation, abdominal fistula or abdominal abscess within the previous 6 months;
• Patients with past and current objective evidence of a history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, and severe impairment of lung function;
• Previously or currently suffering from congenital or acquired immunodeficiency diseases;

Sponsors & Collaborators

• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: lead

Related Publications (6)

• Park JW, Chen M, Colombo M, Roberts LR, Schwartz M, Chen PJ, Kudo M, Johnson P, Wagner S, Orsini LS, Sherman M. Global patterns of hepatocellular carcinoma management from diagnosis to death: the BRIDGE Study. Liver Int. 2015 Sep;35(9):2155-66. doi: 10.1111/liv.12818. Epub 2015 Mar 25.

  PMID: 25752327 BACKGROUND

• He MK, Le Y, Li QJ, Yu ZS, Li SH, Wei W, Guo RP, Shi M. Hepatic artery infusion chemotherapy using mFOLFOX versus transarterial chemoembolization for massive unresectable hepatocellular carcinoma: a prospective non-randomized study. Chin J Cancer. 2017 Oct 23;36(1):83. doi: 10.1186/s40880-017-0251-2.

  PMID: 29061175 BACKGROUND

• Gourd K, Lai C, Reeves C. ESMO Virtual Congress 2020. Lancet Oncol. 2020 Nov;21(11):1403-1404. doi: 10.1016/S1470-2045(20)30585-4. Epub 2020 Sep 24. No abstract available.

  PMID: 32979983 BACKGROUND

• 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.

  PMID: 31070690 BACKGROUND

• Bersanelli M, Buti S. From targeting the tumor to targeting the immune system: Transversal challenges in oncology with the inhibition of the PD-1/PD-L1 axis. World J Clin Oncol. 2017 Feb 10;8(1):37-53. doi: 10.5306/wjco.v8.i1.37.

  PMID: 28246584 BACKGROUND

• Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4.

  PMID: 33538338 RESULT

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Folfox protocol; Oxaliplatin; Leucovorin; Fluorouracil; toripalimab; donafenib

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

Study Officials

• Zhiyu Xiao

  Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yongcong Yan

CONTACT

+86 020 34070390; yanyc3@mail.sysu.edu.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

Study Record Dates

• First Submitted: August 7, 2022
• First Posted: August 9, 2022
• Study Start: September 1, 2022
• Primary Completion: September 1, 2023
• Study Completion: September 1, 2024
• Last Updated: August 18, 2022

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share