Lenvatinib and Adebrelimab Combined With GEMOX in the Perioperative Treatment of Potentially Resectable Intrahepatic Cholangiocarcinoma

A Single-arm, Prospective Clinical Study of Lenvatinib and Adebrelimab Combined With GEMOX in the Perioperative Treatment of Potentially Resectable Intrahepatic Cholangiocarcinoma

A single-arm, prospective clinical study was conducted to enroll 20 subjects. Each subject was treated with oral Lenvatinib + Adebrelimab + GEMOX (gemcitabine + oxaliplatin). The treatment phase before surgery was 3 cycles, and the evaluation was performed every 2 cycles. The evaluation was repeated before surgery, and the decision of surgery was made according to the evaluation results.

To evaluate the efficacy and safety of Lenvatinib and Adebrelimab combined with GEMOX in the perioperative treatment of potentially resectable intrahepatic cholangiocarcinoma.

Study Overview

• Status: Not yet recruiting
• Conditions: Intrahepatic Cholangiocarcinoma
• Intervention / Treatment: Drug: Lenvatinib

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Zunyi Zhang; Phone Number: 86-15827413728; Email: zunyizhangtjmu@163.com
• Study Contact Backup: Name: Guan Tan; Phone Number: 86-15971812255; Email: d202382316@hust.edu.cn

Study Locations

• China
  • Wuhan, China
    • Tongji Hospital
    • Contact: Zunyi Zhang; Phone Number: 86-15827413728; Email: zunyizhangtjmu@163.com
    • Contact: Guan Tan; Phone Number: 86-15971812255; Email: d202382316@hust.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Voluntarily participated in this study, signed informed consent, aged 18-80 years
• Patients with locally advanced intrahepatic cholangiocarcinoma: (meet at least one of the following) A, the number of intrahepatic tumors was 2-3 B, the intrahepatic tumor is single but >5cm in diameter C, the tumor was close to the 1/2 grade branch of the hepatic pedicle, making RO resection difficult D. Lymph node metastasis: MRI or PET/CT suggested regional lymph node metastasis
• The WHO/ECOG PS score was 0-1
• Imaging examination (CT/MRI/PET-CT) showed no distant metastasis
• Child-Pugh grade: A (≤6 points)
• Expected survival time ≥6 months
• No previous systemic treatment for hepatocellular carcinoma, including chemotherapy, targeted therapy, immunotherapy, etc. Patients who had undergone previous curative surgery or curative ablation were allowed, except those who had a recurrence within 2 years after curative surgery and those who had received other previous local treatment
• If you have hepatitis B virus (HBV) infection, such as HBsAg positive, you need to test HBV-DNA, and HBV-DNA should be less than 500IU/mL (; Patients with HBV-DNA of more than 500 IU per milliliter received antiviral therapy (only nucleoside agents such as entecavir, tenofovir dipivoxil fumarate, and tenofovir propofol fumarate tablets) for at least 1 week before randomization and had a decrease in viral copy number by a factor of more than 10. For patients with HBV infection, antiviral therapy should be received throughout the study period. Patients who are positive for hepatitis C virus (HCV) -RNA must receive antiviral therapy according to treatment guidelines

• Organs and bone marrow are sufficiently functional, defined as follows:

  1. hemoglobin ≥9g/dL
  2. absolute neutrophil count ≥1.5 × 109/L
  3. platelet count ≥ 100 × 109/L
  4. serum bilirubin ≤2.0× upper limit of normal (ULN); This condition does not apply to patients with proven Gilbert's syndrome. Any clinically significant biliary obstruction had to be relieved prior to enrollment in the study.
  5. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) should be ≤2.5×ULN. For patients with liver metastases, ALT and AST should be ≤5 × ULN.

Exclusion Criteria:

• The investigator deemed the subject unfit to participate in the study
• Have active autoimmune disease or a history of autoimmune disease with possible recurrence (including but not limited to autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism)
• Use of immunosuppressant or systemic hormone therapy to achieve immunosuppression within 2 weeks before treatment (dose >10mg/ day of prednisone or other effective hormones)
• patients with active infection, unexplained fever ≥38.5℃ within 1 week before randomization, or white blood cell count >15×109/L during screening; Therapeutic antibiotics, administered orally or intravenously, were given within 2 weeks before randomization
• Patients with innate or acquired immune deficiency (e.g., HIV infection)
• History of other primary malignancies, with the exception of malignancies treated with curative treatment, known absence of active disease ≥5 years before the first study intervention, and low potential risk of recurrence; Basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or lentigo maligna that has received potentially curative treatment; Or carcinoma in situ that has been adequately treated without evidence of disease
• Patients with clinically significant bleeding symptoms or a clear bleeding tendency within 6 months before treatment, such as gastrointestinal bleeding, severe esophagogastric varices, hemorrhagic gastric ulcer, or angiitis, can be reexamined if fecal occult blood is positive at baseline, and if it is still positive after reexamination, gastroscopy is required
• Known inherited or acquired bleeding (e.g. coagulopathy) or thrombophilia, such as in patients with hemophilia, coagulation disorders, thrombocytopenia, etc.; Currently receiving full-dose oral or injectable anticoagulants or thrombolytic agents for therapeutic purposes (prophylactic use such as low-dose aspirin is allowed)
• Known allergies to any study drug or excipients
• Participate in other drug clinical trials within 4 weeks before randomization
• Pregnant or lactating women
• Other factors considered by the investigator to be unsuitable for participation in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lenvatinib and Adebrelimab Combined With GEMOX（Gemcitabine and oxaliplatin）; Lenvatinib（oral，12mg once daily if body weight ≥60Kg; Body weight < 60Kg, 8mg/ day）； Adebrelimab（intravenous drip，1200mg once every 3 weeks）； GEMOX（intravenous drip，Gemcitabine 1000mg/m2, 2 times every 3 weeks d1+d8; intravenous drip，Oxaliplatin, 100mg/m2, was given every 3 weeks）	Drug: Lenvatinib; Lenvatinib（oral，12mg once daily if body weight ≥60Kg; Body weight < 60Kg, 8mg/ day）； Adebrelimab（intravenous drip，1200mg once every 3 weeks）； GEMOX（intravenous drip，Gemcitabine 1000mg/m2, 2 times every 3 weeks d1+d8; intravenous drip，Oxaliplatin, 100mg/m2, was given every 3 weeks）; Other Names: Adebrelimab; GEMOX（Gemcitabine and oxaliplatin）

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	Objective Response Rate	through study completion, an average of 1 year
DFS	Disease Free Survival	through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	Overall Survival	Up to 24 months
R0 resection rate	The tumor was completely removed with negative margins, meaning no residual tumor	1 year
DCR	Disease Control Rate	DCR will be calculated as the percentage of patients who achieved Stable Disease(SD) or better for more than 8 weeks (RECIST v1.1)
EFS	Event Free Survival	Up to 12/24 months

Collaborators and Investigators

• Sponsor: Zhiyong Huang
• Investigators: Principal Investigator: Zhiyong Huang, Tongji Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): May 30, 2024
• Primary Completion (Estimated): April 20, 2025
• Study Completion (Estimated): May 30, 2025

Study Registration Dates

• First Submitted: May 7, 2024
• First Submitted That Met QC Criteria: May 11, 2024
• First Posted (Actual): May 16, 2024

Study Record Updates

• Last Update Posted (Actual): May 22, 2024
• Last Update Submitted That Met QC Criteria: May 21, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• 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; Protein Kinase Inhibitors; Oxaliplatin; Lenvatinib; Gemcitabine
• Other Study ID Numbers: IEC-ZN-01-AF 09

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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