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

NCT07025174 | Recruiting Phase 2 DMC

• 1 other identifier: IIT20250065C-R1
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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

Keywords

Biliary tract cancer; Immunotherapy; Anti-angiogenic therapy; Anlotinib; Sequential therapy

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS) of Second-Line Treatment

  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.

  From the start of second-line treatment until disease progression or death from any cause, assessed up to 24 months

Study Arms (2)

Standard Chemotherapy First-line

ACTIVE COMPARATOR

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.

Drug: Gemcitabine, Cisplatin; Drug: Anlotinib; Drug: Oxaliplatin + 5-Fluorouracil/Leucovorin

Immunotherapy Plus Chemotherapy First-line

EXPERIMENTAL

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.

Drug: PD-1/CTLA-4 Dual Functional Antibody; Drug: Gemcitabine, Cisplatin; Drug: Anlotinib; Drug: Oxaliplatin + 5-Fluorouracil/Leucovorin

Interventions

PD-1/CTLA-4 Dual Functional Antibody 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.

Immunotherapy Plus Chemotherapy First-line

Gemcitabine, Cisplatin DRUG

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

Immunotherapy Plus Chemotherapy First-line; Standard Chemotherapy First-line

Anlotinib DRUG

10mg po d1-14 q3w

Immunotherapy Plus Chemotherapy First-line; Standard Chemotherapy First-line

Oxaliplatin + 5-Fluorouracil/Leucovorin 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; Standard Chemotherapy First-line

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• First Affiliated Hospital of Zhejiang University: lead

Study Sites (1)

The First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310003, China

RECRUITING

MeSH Terms

Conditions

Bile Duct Neoplasms; Gallbladder Neoplasms; Biliary Tract Neoplasms; Cholangiocarcinoma

Interventions

Gemcitabine; Cisplatin; anlotinib; Oxaliplatin; Fluorouracil; Leucovorin

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Gallbladder Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals; Uracil; Pyrimidinones; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Study Officials

• Tingbo Liang, MD

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhen Liu, MD

CONTACT

86-571-87235407; liuzhen@cancer.ac.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2025
• First Posted: June 17, 2025
• Study Start: June 1, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: June 17, 2025

Record last verified: 2025-05

Locations

CN (1)