Liver Transplantation for Non-resectable Perihilar Cholangiocarcinoma: a Prospective Exploratory Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Overall survival
研究概览
简要总结
The study will investigate whether liver transplantation provides increased survival, low side effects and good quality of life in patients with bile duct cancer where the tumor cannot be removed by normal surgery. Analyzes of blood and tissue samples from the tumor will be investigated to see if the analyzes can indicate who may have recurrence of the disease after liver transplantation. Furthermore, the effect of chemotherapy on normal liver and tumor tissues in the liver that are removed during transplantation will be investigated.
详细描述
Liver transplantation (Lt) is an established method of treatment for acute and chronic liver failure. One and five- year survival after Lt is approximately 90% and 80%, respectively. Currently, Lt is a treatment option for selected patients with primary carcinomas in the liver and in patients with liver metastases from neuroendocrine tumors. The prerequisite is that there is no extra-hepatic tumor growth and that the primary tumor is removed. Lt for cancer comprises of 14% of all Lts in Europe (www.etlr.org). Types of primary carcinomas eligible for transplantation today include hepatocellular carcinoma (HCC), hepatoblastoma, hemangioendothelioma, and perihilar cholangiocarcinoma (pCCA), the latter in clinical protocols. The most common secondary hepatocarcinomas are neuroendocrine tumours (carcinoid tumours and gastrinomas). The International Registry of Hepatic Tumors in Liver Transplantation show that survival of HCC patients after transplantation is above 70% and 60% at 1 and 5 years, respectively. Recent studies on HCC and liver transplantation have shown even better results when patients are treated with an immunosuppressive regimen containing the antiproliferative agent rapamycin. For hepatoblastoma (children) and malign hemangioendotheliaoma the five-year survival is between 50-60% and for intestinal sarcomas and neuroendocrine tumours it is approximately 35-40%. In patients transplanted for pCCA using a multimodal approach utilizing neoadjuvant radiation, chemotherapy and liver transplantation (Mayo protocol) 5-year patient survival of >80% in selected patients compared to a corresponding 21% five-year survival in liver resection.
Malignancy of the biliary tree (cholangiocarcinoma, CCA) is a rare cancer with an annual incidence around 150 cases in Norway. Cholangiocarcinoma can be subdivided into distal, perihilar, and intrahepatic according to their anatomical location5. Although rare, intrahepatic cholangiocarcinoma (iCCA) constitutes the second most common primary liver cancer after hepatocellular carcinoma, and the worldwide incidence of iCCA is increasing. Despite improvements in multidisciplinary management, patients with CCA have a poor outcome and only 20% of patients are eligible for surgical resection, with 5-year overall survival of less than 10% for all patients. The only potentially curative treatment option is surgical resection with complete excision of tumor with negative margins.
An Irish study with liver transplantation for patients with unresectable hilar CCA who received neoadjuvant chemoradiotherapy had 1- , 3- and 5-year survival of 81%, 69% and 62% respectively, of the transplanted patients. We have recently started a prospective exploratory study, TESLA trial, investigating Lt in non-resectable iCCA with stable disease on oncological treatment.
Building on these results in addition to our own experience with liver transplantation for non-resectable colorectal liver metastases, we want to investigate in the TESLA-II trial the role of Lt in selected patients with unresectable pCCA, who fulfill the inclusion criteria.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Radiologically strong suspicion of pCCA
- •Tumor can involve intrahepatic portal vein without thrombosis of extrahepatic portal vein
- •Tumor can involve hepatic artery distal to gastroduodenal artery or involve replaced hepatic artery
- •First time pCCA
- •Disease deemed not eligible for liver resection based on tumor location or underlying liver dysfunction
- •No extrahepatic disease, or lymph node involvement detected on imaging
- •No signs of extrahepatic metastatic disease according to PET-CT scan
- •No signs of extrahepatic metastatic disease according to CT or MR (chest/abdomen/pelvis) scan within 4 weeks prior to the faculty meeting at the transplant unit
- •At least 18 years of age
- •Good performance status, Eastern Cooperative Oncology Group (ECOG) score: 0 or 1
- •Satisfactory blood tests Hb >10g/dl, neutrophiles >1.0 (after any G-CSF), TRC >50, Bilirubin<3 x upper normal level, ASAT, ALAT<5 x upper normal level, Creatinine <1.5 x upper normal level. Albumin above lower normal level, Normal IgG4 levels
- •Signed informed consent and expected cooperation of the patients for the treatment and follow up must be obtained and documented according to GCP, and national/local regulations
- •Received chemotherapy for at least 6 months with at least 10% response according ti RECIST criteria and with no progression of disease at time of Lt
- •At least 10 months from diagnosis
- •Patient must be accepted for transplantation before progressive disease
- •Twelve months or more time span from the diagnosis of pCCA and date of being listed for liver transplantation
排除标准
- •Tumor involving common hepatic artery, celiac trunck or superior mesenteric artery the tumor
- •Tumor involving main portal vein
- •Tumor involving inferior vena cava
- •Perforation of the visceral peritoneum
- •Weight loss >15% the last 6 months
- •Patient BMI > 30
- •Other malignancies, except curatively treated more than 5 years ago without relapse
- •Known history of human immunodeficiency virus (HIV) infection
- •Prior history of solid organ or bone marrow transplantation
- •Substance abuse, medical, psychological, or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
- •Known hypersensitivity to rapamycin
- •Prior extrahepatic metastatic disease
- •Women who are pregnant or breast feeding
- •Any reason why, in the opinion of the investigator, the patient should not participate
结局指标
主要结局
Overall survival
时间窗: From screening and until 36 months after inclusion
Patient record
次要结局
- Diagnosis of other malignancies(Up to 10 years after liver transplantation)
- Overall survival from time of relapse(From time of relapse and until 36 months after inclusion)
- Time to start of new treatment/change in strategy(Immediately after liver transplatation to start of new treatment)
- Survival in relation to biological markers(After Liver Transplant until 10 years after liver transplantation)
- Disease free survival(After liver transplantation and up 10 years after liver transplantation)
- Complication according to Clavien-Dindo grad 3-5(Up to 90 days after liver transplantation)
- Quality of life (EORTC QLQ-C30), time to decrease in physical function and global health score(Up to 10 years after liver transplantation)
研究者
Sheraz Yaqub
Assoc Professor, MD PhD FEBS
Oslo University Hospital