Observation Study of Sequential Regorafenib Plus ICIs After HAIC for Advanced Hepatocellular Carcinoma

NCT05573282 | Unknown

• 1 other identifier: B2022-334-01
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 2

Brief Summary

Hepatic artery infusion chemotherapy (HAIC) has shown promising outcomes in patients with advanced hepatocellular carcinoma (HCC). Some patients can be converted to loco-regional therapies after 4-6 cycles of HAIC treatment. But most of these patients still need to concern the sequential treatment after standard HAIC treatment (4-6 cycles). Combination of anti-angiogenic molecular targeted therapy and immune checkpoint inhibitor (ICI) therapy has shown promising antitumor activity in HCC. Regorafenib is one of the standard second-line systemic therapy for advanced HCC. In this study, we will evaluate the efficacy and safety of sequential therapies of Regorafenib plus ICI in patients with advanced HCC who have completed 4-6 cycles of HAIC.

Conditions

Hepatocellular Carcinoma

Keywords

Hepatic arterial infusion chemotherapy; Regorafenib; Immunocheckpoint inhibitor

Outcome Measures

Primary Outcomes (2)

• Overall Survival

  Absence of death of any cause

  2-years Followed up

• Progress Free Survival

  Absence of disease progression other than death

  2-years Followed up

Secondary Outcomes (3)

• Tumor local control

  2-years Followed up

• Adverse Events (AEs)

  2-years Followed up

• Tumor Response

  2-years Followed up

Study Arms (1)

Sequential therapy of Regorafenib combined with ICIs

Sequential therapy of Regorafenib combined with one kind of ICIs after standard HAIC treatment in advanced hepatocellular carcinoma (HCC). ICIs: atezolizumab, pembrolizumab, nivolumab, camrelizumab, tislelizumab, sintilimab or other ICIs.

Other: Regorafenib combine with ICIs

Interventions

Regorafenib combine with ICIs OTHER

Regorafenib: 80mg/day, PO, QD, d1～d21, Q4W ICIs: 200mg/day, IV, d1,Q3W

Sequential therapy of Regorafenib combined with ICIs

Eligibility Criteria

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

Study Population

Sequential and maintenance therapy of Regorafenib plus ICIs in andvanced HCC patients who have completed standard HAIC.

You may qualify if:

• Written informed consent must be obtained prior to any screening procedures.
• Cytohistological confirmation is required for diagnosis of HCC.
• Patients with advanced (unresectable and/or metastatic, stage C based on Barcelona-Clinic Liver Cancer \[BCLC\] staging classification) hepatocellular carcinoma who have completed 4-6 cycles HAIC. Treated efficacy evaluation has confirmed that these patients are not suitable for loco-regional therapies or surgical resection.
• At least one tumor lesion meeting measurable disease criteria as determined by RECIST v1.1. Lesions previously treated with local therapy, such as radiation therapy, hepatic arterial embolization, radiofrequency ablation, and percutaneous interventional therapy should not be selected unless progression is noted at baseline, in which case, these lesions would be considered as non-target lesions.
• Current cirrhotic status of Child-Pugh class A-B, with no encephalopathy. Ascites controlled by diuretics is permitted in this study.
• Availability of a representative tumor tissue specimen (archival tumor tissue is allowed) at pre-screening.
• Eastern Cooperative Oncology Group Scale for Assessment of Patient Performance Status ≤ 2.
• Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial and 4 weeks after the completion of trial.
• Adequate bone marrow, liver and renal function as assessed by central lab by means of the following laboratory requirements from samples within 7 days prior to procedure:
• Hemoglobin \> 100g/L
• Absolute neutrophil count \>3.0 ×109/L
• Neutrophil count \> 1.5 ×109/L
• Platelet count ≥ 50.0 ×109/L
• Total bilirubin \< 51 μmol/L
• Alanine transaminase (ALT) and aminotransferase (AST) \< 5 x upper limit of normal

You may not qualify if:

• A history of liver decompensation, such as refractory ascites, gastrointestinal bleeding, or hepatic encephalopathy; Uncontrolled complications, including but not limited to: Persistent or activity (except the HBV and HCV) infection, symptoms of congestive heart failure and uncontrolled diabetes, uncontrolled hypertension, unstable angina, uncontrolled arrhythmias, active ILD, severe chronic GI disease accompanied by diarrhea, or compliance with requirements may limit the research, resulted in significant increase risk of AE or influence Subjects provided psychiatric/social problem status on their ability to provide written informed consent. A history of active primary immunodeficiency or human immunodeficiency virus; Active or previous records of autoimmune disease or inflammatory diseases, including inflammatory bowel disease (e.g., colitis or Crohn's disease\], diverticulitis, except \[diverticulosis\], systemic lupus erythematosus (SLE), sarcoidosis syndrome or Wegener syndrome (e.g., granulomatous vasculitis, gray's disease, rheumatoid arthritis, the pituitary gland inflammation and uveitis\]).
• Known to produce allergic or hypersensitive reactions to any study drug or any excipient thereof;
• Significant clinical gastrointestinal bleeding or a potential risk of bleeding was identified by the investigator during the 30 days prior to study entry.
• Tumors of the central nervous system, including metastatic brain tumors;
• Pregnant women or breast-feeding patients;
• Complicated with other malignant tumors:
• Malignant tumors that have been treated for therapeutic purposes, have no known active disease for 5 years prior to the first administration of the study drug, and have a low potential risk of recurrence.
• Fully treated non-melanoma skin cancer or malignant freckle moles with no evidence of disease.
• Fully treated carcinoma in situ without evidence of disease.
• Prior to the initial dosing of the study drug, they had received anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapy.
• Has received anti-tumor system therapy for HCC. Non-anti-tumor purpose combined hormone therapy (e.g., hormone replacement therapy) is excluded.
• Is currently using, or has used an immunosuppressive drug within 14 days prior to the first dose of the investigational drug. This standard has the following exceptions:
• intranasal, inhaled, topical or topical steroids. (e.g., intraarticular)
• Systemic corticosteroid therapy not exceeding 10 mg/ day of prednisone or its physiological equivalent as a prophylactic use of steroids for hypersensitivity. (e.g., CT scan pretherapy medication)
• Steroids as a prophylactic for allergic reactions.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (2)

Department of Minimally Invasive and Interventional Radiology, Liver Cancer Study and Service Group, Sun Yat-sen University Cancer Center,

Guangzhou, Guangdong, 500060, China

RECRUITING

Sun Yat-sen University Cancer Center

Guanzhou, Guangdong, 510060, China

RECRUITING

Related Publications (3)

• Lyu N, Wang X, Li JB, Lai JF, Chen QF, Li SL, Deng HJ, He M, Mu LW, Zhao M. Arterial Chemotherapy of Oxaliplatin Plus Fluorouracil Versus Sorafenib in Advanced Hepatocellular Carcinoma: A Biomolecular Exploratory, Randomized, Phase III Trial (FOHAIC-1). J Clin Oncol. 2022 Feb 10;40(5):468-480. doi: 10.1200/JCO.21.01963. Epub 2021 Dec 14.

  PMID: 34905388 BACKGROUND

• 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.

  PMID: 29471013 BACKGROUND

• Lyu N, Lin Y, Kong Y, Zhang Z, Liu L, Zheng L, Mu L, Wang J, Li X, Pan T, Xie Q, Liu Y, Lin A, Wu P, Zhao M. FOXAI: a phase II trial evaluating the efficacy and safety of hepatic arterial infusion of oxaliplatin plus fluorouracil/leucovorin for advanced hepatocellular carcinoma. Gut. 2018 Feb;67(2):395-396. doi: 10.1136/gutjnl-2017-314138. Epub 2017 Jun 7. No abstract available.

  PMID: 28592441 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Hepatocellular

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

Study Officials

• Ming Zhao, M.D. & Ph.D.

  Department of Minimally Invasive and Interventional Radiology, Liver Cancer

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ming Zhao, M.D. & Ph.D.

CONTACT

+86-20-87343272; zhaoming@sysucc.org.cn

Ning Lyu, M.D.

CONTACT

+86-20-87343272; lvning@sysucc.org.cn

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 7, 2022
• First Posted: October 10, 2022
• Study Start: October 16, 2022
• Primary Completion: June 1, 2025
• Study Completion: January 1, 2026
• Last Updated: October 18, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)