Sequential Anti-Angiogenic Therapy After Immunotherapy in Advanced Biliary Tract Cancer

Phase 2

Recruiting

• Conditions: Bile Duct Carcinoma; Gall Bladder Cancer; Biliary Tract Cancer; Cholangiocarcinoma
• Interventions: Drug: Gemcitabine, Cisplatin; Drug: PD-1/CTLA-4 Dual Functional Antibody; Drug: Anlotinib; Drug: Oxaliplatin + 5-Fluorouracil/Leucovorin

• Registration Number: NCT07025174
• Lead Sponsor: First Affiliated Hospital of Zhejiang University

Brief Summary

Brief Summary:

This study is for patients with advanced biliary tract cancer (cancer of the bile ducts or gallbladder). The purpose is to find out if using anti-blood vessel formation drugs after immunotherapy treatment can help patients live longer without their cancer getting worse.

What the study compares:

Control group: Patients receive standard chemotherapy as first-line treatment, then chemotherapy plus anlotinib (an anti-blood vessel drug) if their cancer progresses Treatment group: Patients receive chemotherapy plus immunotherapy as first-line treatment, then the same second-line treatment as the control group if their cancer progresses

Who can join:

Patients aged 18-75 with advanced biliary tract cancer that has been confirmed by tissue testing, who have not received immunotherapy or anti-blood vessel drugs before, and who are in good enough health for treatment.

What we want to learn:

The main goal is to see if patients who received immunotherapy first have better outcomes when they later receive anti-blood vessel treatment. We will measure how long patients live without their cancer getting worse during second-line treatment.

Study design:

This is a randomized study, meaning patients are assigned by chance to one of the two treatment groups. About 60 patients will participate across multiple hospitals in China. We will also collect blood and tissue samples to better understand how these treatments work.

The study will help doctors determine if this treatment sequence could become a new standard approach for patients with advanced biliary tract cancer.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-05
• Study Start: 2025-06-01
• Study First Submitted: 2025-06-10
• Study First Submitted QC: 2025-06-10
• Last Update Submitted: 2025-06-10
• Study First Posted: 2025-06-17
• Last Update Posted: 2025-06-17
• Primary Completion: 2026-12-31
• Study Completion: 2027-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

Age 18-75 years at time of enrollment; Histologically or cytologically confirmed advanced or metastatic biliary tract adenocarcinoma (intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, or gallbladder carcinoma); Unresectable locally advanced or metastatic disease not amenable to curative treatment; At least one measurable lesion according to RECIST version 1.1 criteria; ECOG Performance Status 0-1; Life expectancy ≥ 12 weeks; No prior systemic chemotherapy, immunotherapy, or anti-angiogenic therapy for advanced disease (adjuvant therapy completed >6 months prior is allowed); Adequate bone marrow function: ANC ≥1.5×10⁹/L, platelets ≥100×10⁹/L, hemoglobin ≥90 g/L; Adequate liver function: Total bilirubin ≤2.5×ULN, ALT and AST ≤3×ULN (or ≤5×ULN if liver metastases present); Adequate renal function: Serum creatinine ≤1.5×ULN or creatinine clearance ≥50 mL/min; Signed informed consent.

Exclusion Criteria

Mixed histology tumors or neuroendocrine components; Active central nervous system metastases (treated and stable metastases >4 weeks allowed); History of other malignancies within 5 years (except adequately treated basal cell carcinoma, squamous cell carcinoma of skin, or carcinoma in situ); Active autoimmune disease requiring systemic treatment; History of severe allergic reactions to monoclonal antibodies or study drug components; Uncontrolled hypertension (>140/90 mmHg despite medication); Significant cardiovascular disease including unstable angina, myocardial infarction within 6 months, or NYHA Class III-IV heart failure; Active bleeding or bleeding tendency, thrombosis, or use of anticoagulants; Major surgery within 4 weeks or minor surgery within 2 weeks; Active infection requiring systemic treatment; Pregnancy or breastfeeding; HIV infection, active hepatitis B or C infection; Psychiatric illness that would limit compliance with study requirements.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard Chemotherapy First-line	Gemcitabine, Cisplatin	Patients receive standard gemcitabine plus cisplatin (GP) chemotherapy as first-line treatment for up to 6 cycles. Upon disease progression, patients receive second-line treatment with XELOX or FOLFOX chemotherapy plus anlotinib.
Standard Chemotherapy First-line	Anlotinib	Patients receive standard gemcitabine plus cisplatin (GP) chemotherapy as first-line treatment for up to 6 cycles. Upon disease progression, patients receive second-line treatment with XELOX or FOLFOX chemotherapy plus anlotinib.
Standard Chemotherapy First-line	Oxaliplatin + 5-Fluorouracil/Leucovorin	Patients receive standard gemcitabine plus cisplatin (GP) chemotherapy as first-line treatment for up to 6 cycles. Upon disease progression, patients receive second-line treatment with XELOX or FOLFOX chemotherapy plus anlotinib.
Immunotherapy Plus Chemotherapy First-line	PD-1/CTLA-4 Dual Functional Antibody	Patients receive gemcitabine plus cisplatin (GP) chemotherapy combined with PD-1/CTLA-4 dual functional antibody as first-line treatment for up to 6 cycles. Upon disease progression, patients receive the same second-line treatment as the control group with XELOX or FOLFOX chemotherapy plus anlotinib.
Immunotherapy Plus Chemotherapy First-line	Gemcitabine, Cisplatin	Patients receive gemcitabine plus cisplatin (GP) chemotherapy combined with PD-1/CTLA-4 dual functional antibody as first-line treatment for up to 6 cycles. Upon disease progression, patients receive the same second-line treatment as the control group with XELOX or FOLFOX chemotherapy plus anlotinib.
Immunotherapy Plus Chemotherapy First-line	Anlotinib	Patients receive gemcitabine plus cisplatin (GP) chemotherapy combined with PD-1/CTLA-4 dual functional antibody as first-line treatment for up to 6 cycles. Upon disease progression, patients receive the same second-line treatment as the control group with XELOX or FOLFOX chemotherapy plus anlotinib.
Immunotherapy Plus Chemotherapy First-line	Oxaliplatin + 5-Fluorouracil/Leucovorin	Patients receive gemcitabine plus cisplatin (GP) chemotherapy combined with PD-1/CTLA-4 dual functional antibody as first-line treatment for up to 6 cycles. Upon disease progression, patients receive the same second-line treatment as the control group with XELOX or FOLFOX chemotherapy plus anlotinib.

Primary Outcome Measures

Name	Time	Method
Progression-Free Survival (PFS) of Second-Line Treatment	From the start of second-line treatment until disease progression or death from any cause, assessed up to 24 months	Progression-free survival defined as the time from initiation of second-line chemotherapy plus anlotinib treatment until radiographic disease progression per RECIST 1.1 criteria or death from any cause, whichever occurs first. Disease progression will be assessed by CT or MRI imaging every 2 treatment cycles (approximately every 6 weeks). This outcome measure specifically evaluates whether patients who received first-line immunotherapy plus chemotherapy have improved PFS during second-line anti-angiogenic treatment compared to patients who received first-line chemotherapy alone.

Trial Locations

Locations (1)

The First Affiliated Hospital, Zhejiang University School of Medicine; 🇨🇳 Hangzhou, Zhejiang, China