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)
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 25
- 试验地点
- 2
- 主要终点
- Transplant Completion Rate, TCR
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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:
- •Bile duct invasion: involvement of bilateral secondary bile ducts.
- •Portal vein invasion: involvement of unilateral or bilateral branches and the main trunk.
- •Hepatic artery invasion: involvement of unilateral or bilateral branches.
- •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
- •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:
- •Hemoglobin ≥ 90 g/L.
- •Absolute neutrophil count ≥ 1.5 × 10^9/L.
- •Platelet count ≥ 100 × 10^9/L.
- •Liver function classified as Child-Pugh A, with total bilirubin ≤ 3 times the upper limit of normal (ULN).
- •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.
- •Serum creatinine ≤ 1.5 times ULN; endogenous creatinine clearance rate ≥ 50 ml/min (Cockcroft-Gault formula).
- •Urine protein < (++), or 24-hour urine protein < 1.0 g.
- •The patient has normal coagulation function and no active bleeding:
- •International normalized ratio (INR) ≤ 1.
- •Activated partial thromboplastin time (APTT) ≤ 1.5 times ULN.
- •If the subject has HBV or HCV infection, the following conditions must be met:
- •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.)
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: PD -1/PD-L1 monoclonal antibody plus radiotherapy and liver transplantation (Procedure)
结局指标
主要结局
Transplant Completion Rate, TCR
时间窗: 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.
次要结局
未报告次要终点