Anti-blood-vessel therapy after immunotherapy for advanced bile duct or gallbladder cancer.
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
This study will test whether giving the anti-angiogenic drug anlotinib after first-line immunotherapy helps people with advanced bile duct or gallbladder cancer live longer without their disease getting worse.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 60 (estimated) |
| Ages | 18 Years to 75 Years |
| Sex | All |
| Sponsor | First Affiliated Hospital of Zhejiang University Academic / other |
| Drugs / interventions | chemotherapy, immunotherapy, anlotinib |
| Locations | 1 site (Hangzhou, Zhejiang) |
| Trial ID | NCT07025174 on ClinicalTrials.gov |
What this trial studies
This randomized Phase 2 trial enrolls adults 18–75 with histologically confirmed unresectable or metastatic biliary tract adenocarcinoma and ECOG performance status 0–1. Participants are assigned to receive either standard gemcitabine/cisplatin chemotherapy as first-line therapy or gemcitabine/cisplatin combined with a PD-1/CTLA-4 dual functional antibody as first-line therapy; patients in both arms receive the same second-line options including anlotinib if disease progresses. The primary endpoint is progression-free survival, with secondary endpoints including overall survival, response rate, and safety. The trial is conducted at a single center in Hangzhou, China.
Who should consider this trial
Good fit: Ideal candidates are adults 18–75 with confirmed unresectable or metastatic biliary tract adenocarcinoma, at least one measurable lesion, ECOG 0–1, adequate organ function, and no prior systemic chemotherapy, immunotherapy, or anti-angiogenic therapy for advanced disease.
Not a fit: Patients with poor performance status, mixed or neuroendocrine tumor histology, prior immunotherapy or anti-angiogenic treatment for advanced disease, or significant organ dysfunction are unlikely to benefit from this protocol.
Why it matters
Potential benefit: If successful, this sequence could extend progression-free survival and may improve overall survival for people with advanced biliary tract cancer.
How similar studies have performed: Adding immunotherapy to first-line chemotherapy has shown benefit in biliary tract cancer in other trials, but sequential use of anti-angiogenic therapy after immunotherapy is a relatively new approach with limited prior data.
Eligibility criteria
Show full inclusion / exclusion 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.
Where this trial is running
Hangzhou, Zhejiang
- The First Affiliated Hospital, Zhejiang University School of Medicine — Hangzhou, Zhejiang, China (Recruiting)
Study contacts
- Principal investigator: Tingbo Liang, MD — Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine
- Study coordinator: Zhen Liu, MD
- Email: liuzhen@cancer.ac.cn
- Phone: 86-571-87235407
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.