GEMOX-HAIC Plus GEM-SYS in Combination With Lenvatinib and PD-1 Inhibitor for Large Unresectable ICC

Hepatic Arterial Infusion of GEMOX Plus Systemic Gemcitabine Chemotherapy Combined With Lenvatinib and PD-1 Inhibitor in Large Unresectable Intrahepatic Cholangiocarcinoma

This study aimed to preliminarily evaluate the clinical efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) of gemcitabine and oxaliplatin (GEMOX) plus systemic gemcitabine chemotherapy (GEM-SYS) combined with lenvatinib and programmed cell death protein-1 (PD-1) inhibitor in patients with large unresectable intrahepatic cholangiocarcinoma (uICC). Large uICC patients who underwent GEMOX-HAIC (Day 1) and GEM-SYS (Day 8) (3w/cycle) combined with lenvatinib and PD-1 inhibitor between November 2019 and December 2022 were enrolled. Clinical data were retrospectively collected to analyze local tumor response, progression-free survival (PFS), overall survival (OS), and adverse events (AEs). Tumor response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. AEs were evaluated by the common terminology criteria for adverse events (CTCAE) version 5.0. In this study, OS was the primary endpoint, and progression-free survival (PFS) was the secondary endpoint.

Study Overview

• Status: Recruiting
• Conditions: Intrahepatic Cholangiocarcinoma
• Intervention / Treatment: Drug: Gemcitabine-Oxaliplatin Regimen

• Study Type: Observational
• Enrollment (Estimated): 21

Contacts and Locations

• Study Contact: Name: Jia-yan Ni, M.D.; Phone Number: 13660140273; Email: nijaiyan3@mail.sysu.edu.cn

Study Locations

• China
  • Guangzhou
    • Guangzhou, Guangzhou, China, 510000
      • Recruiting
      • Sun Yat-sen Memorial Hospital of Sun Yat-sen University
      • Contact: Jia-yan Ni; Phone Number: 13660140273; Email: nijiayan3@mail.sysu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

21 large uICC patients who underwent GEMOX-HAIC (Day 1) and GEM-SYS (Day 8) (3w/cycle) combined with lenvatinib and PD-1 inhibitor between November 2019 and December 2022 were enrolled.

Description

Inclusion Criteria:

(a) age of 18-70 years; (b) Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1; (c) diagnosis of ICC by histopathological examination of tissue biopsy specimens; (d) unresectable ICC confirmed by a multidisciplinary staff including at least one experienced liver surgeon; (e) tumor size larger than 5 cm in maximum diameter; (f) adequate liver function (total bilirubin < 3 times the upper limit of normal and aspartate/alanine transaminases < 5 times the upper limit of normal), adequate renal function (serum creatinine concentration of no more than 1.5 times the upper limit of the normal level), adequate bone marrow function (white blood cell count>3,000/mm3, hemoglobin>9.0g/dl and platelet count >100,000/mm3 ) and adequate coagulation function (prothrombin activity > 40% and international normalized ratio (INR) < 1.26); (g) patients received at least two cycles of GEMOX-HAIC + GEM-SYS combined with lenvatinib and PD-1 inhibitor; (h) patients with regular clinical data for evaluating the clinical efficacy and safety.

Exclusion Criteria:

(a) combined with other malignancies; (b) patients underwent any other chemotherapy regimens before, including gemcitabine and oxaliplatin; (c) patients received previous surgical resection or any other interventional procedures besides HAIC, such as transarterial chemoembolization (TACE), 125I seed implantation, radiofrequency ablation, microwave ablation, cryoablation, or percutaneous ethanol injection, etc.; (d) drug (chemotherapy drugs, lenvatinib, or PD-1 inhibitors) allergy; (e) patients with a history of autoimmune diseases; (f) patients with gastrointestinal bleeding of any grade within 4 weeks prior to the integrated treatment; (g) patients with uncontrolled comorbidities (e.g. general infection, serious dysfunction of heart or kidney, acute hepatitis or pneumonia, chronic obstructive pulmonary disease, or recent stroke).

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
HAIC+SYS+LEN+PD-1i	Drug: Gemcitabine-Oxaliplatin Regimen; Hepatic arterial infusion chemotherapy (HAIC) of gemcitabine and oxaliplatin (GEMOX) plus systemic gemcitabine chemotherapy (GEM-SYS) combined with lenvatinib and programmed cell death protein-1 (PD-1) inhibitor.; Other Names: PD-1 inhibitor; lenvatinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival(OS)	OS was calculated as the duration from the date of the first cycle of GEMOX-HAIC+GEM-SYS to the date of death or last date of follow-up.	1-, 2-, and 3-year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	PFS was defined as the duration from the date of the first cycle of GEMOX-HAIC+GEM-SYS to tumor lesion progression, death, or last follow-up, whichever came first.	1-, 2-, and 3-year

Collaborators and Investigators

• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
• Investigators: Principal Investigator: Jia-yan Ni, M.D., Sun Yat-sem Memorial Hospital, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): July 10, 2024
• Primary Completion (Estimated): July 10, 2025
• Study Completion (Estimated): July 10, 2025

Study Registration Dates

• First Submitted: July 11, 2024
• First Submitted That Met QC Criteria: July 11, 2024
• First Posted (Actual): July 17, 2024

Study Record Updates

• Last Update Posted (Actual): July 17, 2024
• Last Update Submitted That Met QC Criteria: July 11, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Tyrosine Kinase Inhibitor; Hepatic Arterial Infusion Chemotherapy; Immune Checkpoint Inhibitor; Intrahepatic Cholangiocarcinoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Cholangiocarcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Oxaliplatin; Lenvatinib; Immune Checkpoint Inhibitors; Gemcitabine
• Other Study ID Numbers: SYSKY-2024-539-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No