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

Official title

Evaluation of the Effect of Sequential Anti-angiogenic Therapy Following Immune Therapy Progression on Survival in Patients With Advanced Biliary Tract Malignancies: A Randomized, Multi-center, Exploratory Clinical Study

Overview

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.

Interventions

• Drug 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.
• Drug Gemcitabine, Cisplatin
  Gemcitabine 1000 mg/m² d1,8+Cisplatin 25mg/m² d1,8
• Drug Anlotinib
  10mg po d1-14 q3w
• 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)

Primary outcome measures

• Progression-Free Survival (PFS) of Second-Line Treatment [Time frame: From the start of second-line treatment until disease progression or death from any cause, assessed up to 24 months]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The First Affiliated Hospital, Zhejiang University School of Medicine — Hangzhou

Identifiers

NCT: NCT07025174 · IIT20250065C-R1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗