A Prospective, Single-Arm, Phase II Study: PD-L1 Monoclonal Antibody + Chemoradiotherapy as Bridge Therapy to Liver Transplantation for Locally Advanced Perihilar Cholangiocarcinoma (ACHIEVE-LT) (ACHIEVE-LT)

March 11, 2026 updated by: The First Affiliated Hospital with Nanjing Medical University
This study is a prospective, single-arm, phase II clinical trial designed to evaluate the safety and efficacy of PD-L1 monoclonal antibody combined with chemoradiotherapy as a bridge to liver transplantation in patients with locally advanced unresectable perihilar cholangiocarcinoma (pCCA).

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Patients with locally advanced, unresectable pCCA who met the criteria as assessed by a multidisciplinary team (MDT) were enrolled after signing informed consent. They received three cycles of treatment with a PD-L1 monoclonal antibody combined with a gemcitabine + cisplatin regimen, followed by external beam radiotherapy (45 Gy/15 fractions) administered concurrently with oral capecitabine. Subsequently, they entered a maintenance therapy phase with capecitabine until liver transplantation (with a minimum of 4 weeks of discontinuation of immunotherapy prior to transplantation) or until disease progression/intolerable toxicity occurred.

Within two weeks prior to liver transplantation, a PET-CT scan was performed to exclude distant and occult metastases. Patients who passed the PET-CT staging screening and reached the drug washout period proceeded to the transplantation pathway.

Postoperatively, a standard immunosuppressive regimen was adopted, and oral capecitabine was administered for eight cycles as adjuvant therapy. All patients were followed up as scheduled to monitor for recurrence and survival.

Study Type

Interventional

Enrollment (Estimated)

25

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Xiangcheng Li
  • Phone Number: • 86 18951999088
  • Email: drlixc@163.com

Study Contact Backup

Study Locations

  • China
    • Jiangsu
      • Nanjing, Jiangsu, China, 210000
        • Jinling Hospital of Nanjing University
        • Contact:
        • Sub-Investigator:
          • Yuan Cheng
      • Nanjing, Jiangsu, China, 210002
        • The First Affiliated Hospital of Nanjing Medical University
        • Contact:
          • Xiangcheng Li
          • Phone Number: • 86 18951999088
          • Email: drlixc@163.com
        • Contact:
        • Principal Investigator:
          • Xiangcheng Li
        • Sub-Investigator:
          • Changxian Li

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

The patient voluntarily participates in this study and signs an informed consent form.

The patient is aged between 18 and 70 years old.

The patient has pathologically confirmed locally advanced perihilar cholangiocarcinoma (pCCA) without concurrent lymph node or distant metastasis, and meets at least one of the following criteria:

  1. Bile duct invasion: involvement of bilateral secondary bile ducts.
  2. Portal vein invasion: involvement of unilateral or bilateral branches and the main trunk.
  3. Hepatic artery invasion: involvement of unilateral or bilateral branches.
  4. Liver invasion: involvement of liver parenchyma or insufficient residual liver volume.

The patient has at least one measurable lesion (as per RECIST 1.1 criteria). The patient has an ECOG performance status score of 0 to 1. The patient has not received any prior systemic or local therapy.

The patient has adequate organ and bone marrow function, and laboratory test results meet the following requirements:

  1. Hemoglobin ≥ 90 g/L.
  2. Absolute neutrophil count ≥ 1.5 × 10^9/L.
  3. Platelet count ≥ 100 × 10^9/L.
  4. Liver function classified as Child-Pugh A, with total bilirubin ≤ 3 times the upper limit of normal (ULN).
  5. ALT and AST ≤ 3 times ULN; for patients with obstructive jaundice, if liver function indicators meet the inclusion criteria after treatment with PTCD or ERCP, they may be considered for inclusion.
  6. Serum creatinine ≤ 1.5 times ULN; endogenous creatinine clearance rate ≥ 50 ml/min (Cockcroft-Gault formula).
  7. Urine protein < (++), or 24-hour urine protein < 1.0 g.

The patient has normal coagulation function and no active bleeding:

  1. International normalized ratio (INR) ≤ 1.5.
  2. Activated partial thromboplastin time (APTT) ≤ 1.5 times ULN.

If the subject has HBV or HCV infection, the following conditions must be met:

  1. For inactive/asymptomatic HBV carriers or chronic/active HBV carriers: HBV deoxyribonucleic acid (DNA) < 2000 copies/mL during screening. (Note: Patients with HBV DNA > 2000 copies/mL should be treated according to treatment guidelines. Patients receiving antiviral therapy at the time of screening should have HBV-DNA < 2000 copies/mL and continue treatment during the study.)
  2. For subjects infected with HCV: if infection is confirmed by detectable HCV ribonucleic acid (RNA), such subjects cannot be included in the group.

No pregnancy or plans for pregnancy: If you are a woman of childbearing potential (i.e., physically capable of becoming pregnant), you must agree to use effective contraception during the study and for 120 days after the last dose, and have a negative urine or serum pregnancy test within 7 days before the first dose. If you are a non-sterilized male, you need to agree to use effective contraception during the study and for 120 days after the last dose.

-

Exclusion Criteria:

Diagnosed with intrahepatic cholangiocarcinoma, distal cholangiocarcinoma, or gallbladder cancer.

Concurrent lymph node or distant metastasis. Previous systemic treatment for biliary tract tumors. History of severe hypersensitivity reactions to other monoclonal antibodies. Allergy to durvalumab, adebrelimab, or any of their excipients; allergy to gemcitabine or any of its excipients; allergy to cisplatin or any of its excipients.

Presence of pericardial effusion, uncontrolled pleural effusion, or clinically significant ascites within 7 days before treatment, defined as meeting the following criteria: (a) ascites detectable by physical examination during screening, or (b) ascites requiring paracentesis during screening.

Any bleeding or thrombotic disorder or any need for anticoagulants requiring monitoring of the international normalized ratio (e.g., warfarin or similar drugs) within 6 months before treatment initiation.

Presence of any malignancy other than the cholangiocarcinoma under study in this clinical trial and locally recurrent cancers that have been cured (e.g., resected basal cell or squamous cell skin cancer, superficial bladder cancer, cervical or breast cancer in situ, occult thyroid cancer).

Presence of any known central nervous system metastases and/or leptomeningeal disease before treatment.

Any active immunodeficiency or autoimmune disease likely to recur at screening and/or any history of immunodeficiency or autoimmune antibody disease.

Patients with immune system diseases requiring daily administration of more than 10 mg of dexamethasone.

History of interstitial lung disease or non-infectious pneumonitis. Any severe chronic or active infection (excluding viral hepatitis) requiring systemic antibacterial, antifungal, or antiviral treatment (e.g., tuberculosis) before treatment initiation.

Electrocardiogram (ECG) during screening shows a heart rate-corrected QT interval (QTc) (corrected using the Fridericia method) exceeding 450 milliseconds; Note: If any patient has a QTc interval exceeding 450 milliseconds on the first ECG, the ECG will be repeated to confirm the result.

Any of the following cardiovascular risk factors: cardiogenic chest pain within 28 days before treatment, defined as moderate pain limiting daily activities (ADLs). Symptomatic pulmonary embolism within 28 days before treatment. History of acute myocardial infarction within 6 months before treatment.

Any history of heart failure reaching New York Heart Association Class III or IV within 6 months after treatment, ventricular arrhythmia of Grade 2 or higher within 6 months before treatment, cerebrovascular accident (CVA), or transient ischemic attack (TIA) within 6 months before treatment.

Organ transplantation or hematopoietic stem cell transplantation (HSCT) or any major surgery within 28 days before treatment.

Known psychiatric or substance abuse disorders that may interfere with test compliance.

Vaccination with a live vaccine within 28 days before treatment. Note: Seasonal influenza vaccines are generally inactivated and are permitted.

Known history of human immunodeficiency virus (HIV) infection or syphilis infection.

Any history or evidence of disease, treatment, or laboratory abnormalities that may confound test results, interfere with the subject's participation throughout the trial, or be deemed by the principal investigator as not in the subject's best interest.

Pregnancy or lactation, or anticipated pregnancy or childbirth during the planned duration of the trial, from the screening visit to 120 days after the last dose.

Poor compliance as judged by the investigator, or other conditions that make the patient unsuitable for participation in this trial.

Various medical contraindications preventing the use of enhanced imaging (CT or MRI).

The investigator deems the patient unsuitable for inclusion.

-

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: PD-L1 combined with chemoradiotherapy as bridge to liver transplantation

Patients received three cycles of treatment with a PD-L1 monoclonal antibody combined with a gemcitabine + cisplatin regimen, followed by external beam radiotherapy (45 Gy/15 fractions) administered concurrently with oral capecitabine. Subsequently, they entered a maintenance therapy phase with capecitabine until liver transplantation (with a minimum of 4 weeks of discontinuation of immunotherapy prior to transplantation) or until disease progression/intolerable toxicity occurred.

A PET-CT scan was performed within two weeks prior to liver transplantation to exclude distant and occult metastases. Patients who passed the PET-CT staging screening and reached the drug washout period proceeded to the transplantation pathway.

Postoperatively, a standard immunosuppressive regimen was adopted, and oral capecitabine was administered for eight cycles as adjuvant therapy. All patients were followed up as scheduled to monitor for recurrence and survival.
Procedure: PD -1/PD-L1 monoclonal antibody plus radiotherapy and liver transplantation
After receiving treatment with a regimen combining PD-L1 inhibitor, gemcitabine, and cisplatin, patients underwent radiotherapy while concurrently taking oral capecitabine, followed by maintenance therapy with capecitabine until liver transplantation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Transplant Completion Rate, TCR
Time Frame: From the date of randomization until the date of first documented disease progression or the date of death from any cause, whichever occurs first, with an assessment period of up to 48 months.
The proportion of patients who received neoadjuvant therapy and ultimately successfully underwent liver transplantation.
From the date of randomization until the date of first documented disease progression or the date of death from any cause, whichever occurs first, with an assessment period of up to 48 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The First Affiliated Hospital with Nanjing Medical University

Investigators

  • Principal Investigator: Xiangcheng Li, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China 210002

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

March 1, 2026

Primary Completion (Estimated)

March 1, 2029

Study Completion (Estimated)

July 1, 2029

Study Registration Dates

First Submitted

February 13, 2026

First Submitted That Met QC Criteria

March 11, 2026

First Posted (Actual)

March 13, 2026

Study Record Updates

Last Update Posted (Actual)

March 13, 2026

Last Update Submitted That Met QC Criteria

March 11, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2025-SR-1173

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Locally Advanced Perihilar Cholangiocarcinoma

Clinical Trials on PD -1/PD-L1 monoclonal antibody plus radiotherapy and liver transplantation

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in United States

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe