HAIC+Adebrelimab+Lenvatinib for Conversion Treatment of Potentially Resectable, Locally Advanced Biliary Tract Cancer

Hepatic Arterial Infusion Chemotherapy Combined With Adebrelimab and Lenvatinib for Conversion Treatment of Potentially Resectable, Locally Advanced Biliary Tract Cancer: a Single-arm, Exploratory Clinical Study

This is a single-arm, exploratory, phase II trial to evaluate the efficacy and safety of hepatic arterial infusion chemotherapy combined with adebrelimab and lenvatinib for borderline resectable, locally advanced biliary tract cancer.

Study Overview

• Status: Not yet recruiting
• Conditions: Biliary Tract Cancer
• Intervention / Treatment: Drug: Adebrelimab; Drug: Lenvatinib; Procedure: Hepatic Arterial Infusion Chemotherapy

Detailed Description

This study plans to recruit 30 patients with borderline resectable, locally advanced biliary tract cancer who have not received treatment， abserve and evaluate the efficacy and safety of hepatic arterial infusion chemotherapy combined with adebrelimab and lenvatinib.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yubao Zhang, MD; Phone Number: +86 139 3658 8077; Email: zhyb88077@sina.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age: 18 to 75 years old, male or female;
2. Biliary tract malignant tumors confirmed by histology or cytology, with measurable tumor lesions (spiral CT or MR scan ≥10mm, meeting RECIST 1.1 standards);
3. Borderline resectable, locally advanced biliary malignant tumors, including gallbladder cancer, intrahepatic cholangiocarcinoma, hilar cholangiocarcinoma, and distal cholangiocarcinoma;
4. Clinical stage: gallbladder cancer stage: IIIA-IVB; intrahepatic cholangiocarcinoma stage: IIA-IV; hilar cholangiocarcinoma stage: IIIB-IVB; distal cholangiocarcinoma stage: IIIA-IV;
5. Expected survival > 3 months;
6. ECOG PS score: 0-1 points;
7. Liver function classification is Child-Pugh ≤7;
8. Never received prior systemic treatment for biliary tract tumors;
9. No peritoneal metastasis or other distant metastasis;
10. Normal function of major organs;
11. Women of childbearing age must have a negative pregnancy test (βHCG) before starting treatment, and women of childbearing potential and men (who have sexual active with women of childbearing potential) must agree to effective contraception uninterrupted for the duration of the treatment and for 6 months after the last therapeutic dose;
12. Patients voluntarily enrolled in the study by signing an informed consent form.

Exclusion Criteria:

1. Patients diagnosed with periampullary cancer;
2. Previous or concurrent other malignant tumours within 5 years, except cervical carcinoma in situ, cutaneous squamous cell carcinoma or basal cell carcinoma of the skin that has been basically controlled;
3. Those with uncontrolled, symptomatic brain metastases or a history of uncontrollable mental illness or severe intellectual or cognitive dysfunction;
4. Pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia and severely impaired lung function;
5. Suffering from active autoimmune diseases, history of autoimmune diseases, such as interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism; Reduced thyroid function after thyroid hormone replacement therapy can be included;
6. Have a history of immunodeficiency, including testing positive for HIV, suffering from other acquired or congenital immunodeficiency diseases, or a history of organ transplantation and allogeneic bone marrow transplantation;
7. Subjects have cardiovascular clinical symptoms or diseases that cannot be well controlled, including but not limited to: 1) NYHA class II or above heart failure; 2) Unstable angina; 3) Myocardial infarction within 1 year; 4) Clinically significant supraventricular or ventricular arrhythmia requiring clinical intervention;
8. Severe active infection requiring intravenous antibiotic treatment occurs during the screening period;
9. Those who are allergic to experimental drugs;
10. Patients who cannot comply with the trial protocol or cannot cooperate with follow-up visits;
11. Those who the researcher believes are not suitable to participate in this trial.

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: HAIC+Immune-targeted therapy; Hepatic arterial infusion chemotherapy combined with adebrelimab and lenvatinib	Drug: Adebrelimab; Adebrelimab, IV; Other Names: SHR-1316; Drug: Lenvatinib; Lenvatinib, PO; Other Names: Lenvatinib Mesilate Capsules; Procedure: Hepatic Arterial Infusion Chemotherapy; GC regimen±5-FU

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
R0 resection rate	Postoperative staining results showed that the lesion was completely resected, and pathological biopsy of the transverse and longitudinal margins were negative.	up to 24 months
Surgery conversion rate	Proportion of patients who can undergo surgical resection among all enrolled patients	up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AEs	Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v5.0.	up to 24 months
Objective response rate	The proportion of patients whose tumor volume shrinks to a predetermined value and can maintain the minimum time limit, which is the sum of the proportions of complete remission and partial remission.	up to 24 months
pathological complete response rate	After preoperative treatment and surgery, there are no residual viable tumor cells in the tumor bed in the postoperative specimen (%RVT=0)	up to 24 months
Major pathological response rate	After preoperative treatment and surgery, the proportion of residual viable tumor cells in the tumor bed in the postoperative specimen is less than or equal to 10% (%RVT≤10)*	up to 24 months
Recurrence-free survival	Duration from surgical resection to first recurrence or death from any cause	up to 24 months
Overall survival	Overall survival is measured from the first dose of study drug until death from any cause.	up to 24 months

Collaborators and Investigators

• Sponsor: Harbin Medical University
• Investigators: Principal Investigator: Yubao Zhang, MD, Harbin Medical University Affiliated Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2028

Study Registration Dates

• First Submitted: April 24, 2024
• First Submitted That Met QC Criteria: April 24, 2024
• First Posted (Actual): April 29, 2024

Study Record Updates

• Last Update Posted (Actual): April 29, 2024
• Last Update Submitted That Met QC Criteria: April 24, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Lenvatinib; Hepatic Arterial Infusion Chemotherapy; Adebrelimab; Potentially Resectable Biliary Tract Cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Biliary Tract Diseases; Biliary Tract Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Lenvatinib
• Other Study ID Numbers: SHR-1316-HLJ-006

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