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

NCT ID: NCT07025174

Last Updated: 2025-06-17

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-06-01
• Study Completion Date: 2027-12-31

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.

Conditions

Bile Duct Carcinoma; Gall Bladder Cancer; Biliary Tract Cancer; Cholangiocarcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Standard Chemotherapy First-line

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.

Group Type: ACTIVE_COMPARATOR

Gemcitabine, Cisplatin

Intervention Type: DRUG

Gemcitabine 1000 mg/m² d1,8+Cisplatin 25mg/m² d1,8

Anlotinib

Intervention Type: DRUG

10mg po d1-14 q3w

Oxaliplatin + 5-Fluorouracil/Leucovorin

Intervention Type: DRUG

XELOX (oxaliplatin 130mg/m² d1+capecitabine 1000mg/m² d1-14 q3w) or FOLFOX6 (Oxaliplatin 85 mg/m², leucovorin 400 mg/m², fluorouracil 400 mg/m² intravenous bolus followed by fluorouracil 2400 mg/m² 46 hours, q2w)

Immunotherapy Plus Chemotherapy First-line

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.

Group Type: EXPERIMENTAL

PD-1/CTLA-4 Dual Functional Antibody

Intervention Type: DRUG

PD-1/CTLA-4 Dual Functional Antibody (iparomlimab and tuvonralimab injection):

5 mg/kg intravenous infusion every 3 weeks (day 1 of each 21-day cycle) for up to 6 cycles, with potential for maintenance therapy continuation. Used in combination with GP regimen in experimental arm only. This is a novel dual-functional antibody targeting both PD-1 and CTLA-4 pathways simultaneously.

Gemcitabine, Cisplatin

Intervention Type: DRUG

Gemcitabine 1000 mg/m² d1,8+Cisplatin 25mg/m² d1,8

Anlotinib

Intervention Type: DRUG

10mg po d1-14 q3w

Oxaliplatin + 5-Fluorouracil/Leucovorin

Intervention Type: DRUG

XELOX (oxaliplatin 130mg/m² d1+capecitabine 1000mg/m² d1-14 q3w) or FOLFOX6 (Oxaliplatin 85 mg/m², leucovorin 400 mg/m², fluorouracil 400 mg/m² intravenous bolus followed by fluorouracil 2400 mg/m² 46 hours, q2w)

Interventions

PD-1/CTLA-4 Dual Functional Antibody

PD-1/CTLA-4 Dual Functional Antibody (iparomlimab and tuvonralimab injection):

5 mg/kg intravenous infusion every 3 weeks (day 1 of each 21-day cycle) for up to 6 cycles, with potential for maintenance therapy continuation. Used in combination with GP regimen in experimental arm only. This is a novel dual-functional antibody targeting both PD-1 and CTLA-4 pathways simultaneously.

Intervention Type: DRUG

Gemcitabine, Cisplatin

Gemcitabine 1000 mg/m² d1,8+Cisplatin 25mg/m² d1,8

Intervention Type: DRUG

Anlotinib

10mg po d1-14 q3w

Intervention Type: DRUG

Oxaliplatin + 5-Fluorouracil/Leucovorin

XELOX (oxaliplatin 130mg/m² d1+capecitabine 1000mg/m² d1-14 q3w) or FOLFOX6 (Oxaliplatin 85 mg/m², leucovorin 400 mg/m², fluorouracil 400 mg/m² intravenous bolus followed by fluorouracil 2400 mg/m² 46 hours, q2w)

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

First Affiliated Hospital of Zhejiang University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tingbo Liang, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine

Locations

The First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Site Status: RECRUITING

Countries

China

Central Contacts

Zhen Liu, MD

Role: CONTACT

liuzhen@cancer.ac.cn

86-571-87235407

Facility Contacts

Zhen Liu, MD

Role: primary

liuzhen@cancer.ac.cn

86-571-87235407

Other Identifiers

IIT20250065C-R1

Identifier Type: -

Identifier Source: org_study_id