A Single-Arm Nonrandomized Phase II Study of Liver Transplantation in Locally Advanced Unresectable Non-Metastatic Intrahepatic Cholangiocarcinoma Treated With Neoadjuvant Systemic Therapy
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- 5-year Overall Survival Rate (ORS)
研究概览
简要总结
The aim of the current study is to determine the potential efficacy of liver transplantation in the form of patients' overall survival (OS) after neoadjuvant systemic therapy in patients with biologically responsive locally advanced non-metastatic intrahepatic cholangiocarcinoma (iCCA) in comparison to patients historically treated with chemotherapy alone.
详细描述
Research Significance:
Cholangiocarcinoma, which arises from biliary epithelium, can be anatomically subdivided into distal, hilar, and intrahepatic subgroups. Intrahepatic cholangiocarcinoma (iCCA) constitutes the second most common primary liver cancer after hepatocellular carcinoma, with a rising incidence but without parallel advances in treatment or patient outcome. At present, surgical resection is the only widely accepted potentially curative therapy for iCCA; however, 5-year survival rates for resectable disease are less than 25%. This high mortality is attributed to high tumor recurrence. Two-thirds of patients who undergo curative-intent resection for iCCA suffer from postoperative disease recurrence, most commonly in the remnant liver, followed by the peritoneum and abdominal lymph nodes. Approximately 83% of recurrences occur within the first 2 years after resection, suggesting inadequate local tumor control with resection in this highly infiltrative cancer.
Liver transplantation for intrahepatic cholangiocarcinoma:
While liver transplantation has been previously investigated for unresectable iCCA, the outcomes have been poor in comparison to the results for hepatocellular carcinoma, with 18-25% OS and RFS after 5 years; however, most studies evaluated patients with either incidental iCCA or iCCA misdiagnosed prior to transplant as hepatocellular carcinoma (HCC). Thus, iCCA is considered by most centers to be a formal contraindication to liver transplantation.
Neoadjuvant therapy with subsequent liver transplantation for perihilar cholangiocarcinoma:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 89 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years of age on the day of consenting to the study.
- •Patients must have histologically confirmed diagnosis of locally advanced intrahepatic cholangiocarcinoma
- •Confirmed diagnosis of locally advanced unresectable iCCA with no vascular invasion, lymph node, or extrahepatic disease.
- •Unresectable disease based on tumor location or underlying liver disease
- •Patients must have ≥ 6 months of disease stability or tumor regression on neoadjuvant therapy. In cases in which patients had received second-line therapy, disease must also have been controlled for ≥ 6 months on that regimen.
- •Patients who had previous surgical resection for iCCA are eligible if surgery occurred more than 6 months prior to listing, and patients have had ≥ 6 months of disease stability or response on therapy.
- •ECOG performance status ≤1 (Karnofsky ≥70%, see Appendix A).
- •Patients must have organ and marrow function acceptable for liver transplantation per institutional protocol:
- •If history of chronic hepatitis B virus (HBV) infection, viral load should be undetectable on suppressive therapy.
- •If history of chronic hepatitis C virus (HCV) infection, patients should have undetectable HCV viral load.
- •Women of child-bearing years must have contraception plan in place from the time of study enrollment until at least one year following liver transplant.
- •Ability to understand and the willingness to sign a written informed consent document
- •Meets all other medical and psychosocial criteria for liver transplant
- •Demonstrate ability to comply with study procedures
排除标准
- •Age <18 years of age on the day of consenting to the study.
- •Patients who have extrahepatic metastases, lymph node involvement, invasion or encasement of major hepatic vascular structures, perforation of the visceral peritoneum, invasion of extrahepatic structures, invasion of perihilar fat, periductular invasion, concurrent hepatoma or mixed hepatocellular cholangiocarcinoma.
- •Concurrent severe and/or uncontrolled concurrent illness including, but not limited to, ongoing or active infection, acute fulminant liver failure, symptomatic congestive heart failure, unstable angina pectoris, severe uncorrected coronary artery disease, severe cerebrovascular disease, severe pulmonary disease, or psychiatric illness/social situations that would limit compliance with study requirements and that would exclude the patient from eligibility for liver transplantation per institutional protocol.
- •Prior solid organ or bone marrow transplant
- •Dependent on ≥2 IV inotropic support to maintain hemodynamics
- •Previous (within the past 5 years) or concurrent presence of other cancer, except non-melanoma skin cancer and in situ carcinomas.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status Scale score >1 (Karnofsky <70%, see Appendix A).
- •Unable to understand and sign a written informed consent document
- •Untreated viral hepatitis
- •Pregnant or breast-feeding women
- •HIV-infected patients
结局指标
主要结局
5-year Overall Survival Rate (ORS)
时间窗: 5 years from the time of transplant or until death of patient, whichever came first
5-year ORS is the length of time that patients diagnosed with locally advanced non-metastatic intrahepatic cholangiocarcinoma (iCCA) treated with neoadjuvant systemic therapy followed by liver transplant (LT) are still alive post-LT.
次要结局
- Intent-to-treat Overall Survival Rate (ITT ORS)(5 years from time of waitlist or until death of patient, whichever came first)
- Recurrence-free survival (RFS)(From date of transplant until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years)
- Post-liver transplant functional assessments to identify postoperative complications, short-term morbidities, and long-term morbidities(From date of emergence of a post-transplant adverse event until the date the adverse event is designated as resolved by investigator or its effect on patient's condition stabilizes, whichever came first, assessed up to 5 years)
研究者
Keri E. Lunsford
Director of Translational and Surgical Science, Department of Surgery/Assistant Professor, Division of Transplant and Hepatobiliary Surgery/Member, Center for Immunity and Inflammation
Rutgers, The State University of New Jersey