Curative Potential of Liver Transplantation in Patients With Definitively Unresectable Colorectal Liver Metastases (CLM) Treated by Chemotherapy: a Prospective Multicentric Randomized Trial
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 94
- 试验地点
- 2
- 主要终点
- 5 years overall survival (OS)
研究概览
简要总结
This is a multicentric randomized parallel group open trial comparing 5-year survival of chemotherapy followed by LT (Group LT+C) versus chemotherapy alone (Group C) in patients with confirmed unresectable liver-only metastases, well controlled by chemotherapy (no progression) and extensively explored by modern imaging techniques. The primary objective of the trial is to validate in a large multicentric cohort of selected patients the possibility to obtain at least 50% 5-years survival with LT combined to chemotherapy compared to around 10% with chemotherapy alone.
详细描述
Liver transplantation (LT) has recently been proposed as alternative treatment for definitively unresectable colorectal liver metastases in selected patients with a 60% estimated survival at 5 years in a recent prospective Norwegian study. However, disease free survival (DFS) in this preliminary study has been poor with 90% of recurrence after LT.
The objective of our study is to validate LT as a therapeutic option on a large multicentric scale throughout a highly strict policy selection in term of survival, disease free survival and quality of life. In order to reduce selection bias, unresectability criteria and theorical indication to LT will be confirmed by an independent Steering Committee including HPB surgeons, oncologists, radiologists and hepatologists.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥ 18 and ≤ 65 years
- •Good performance status, ECOG 0 or 1 (39).
- •Histologically proved adenocarcinoma in colon or rectum
- •BRAF wild-type CRC on primary tumor or liver metastases
- •High standard oncological surgical resection of the primary defined by :
- •Safe margin of resection
- •Curative resection of primary tumor according to oncological principles
- •TNM adequate staging
- •Absence of local recurrence on colonoscopy performed in the 12 months prior to inclusion (except in case of primary tumor resection < 12 months )
- •Confirmed non resectable colorectal liver metastases by the validation committee
- •≥ 3 months of tumor control during the last chemotherapy line: Stable or Partial Response on RECIST criteria (40)
- •≤ 3 lines of chemotherapy for metastatic disease
- •CEA < 80 microg/L or a decrease ≥ 50% of the highest serum CEA levels observed during the disease
- •Absence of extrahepatic tumor localisation according to CT scan and PET-CT
- •Renal function should be within the normal limits
- •No need for extra-renal purification procedure, hemodialysis or kidney transplantation associated (nephrologist assessment)
- •A platelet count> 80,000 / mm3
- •White blood cell count> 2500 / mm3
- •Eligible for both treatments groups
- •Signed informed consent and expected cooperation of the patient for the treatment and follow up
排除标准
- •Participation refusal
- •No health insurance facilities
- •General contraindication to LT (Severe cardiopulmonary disease or other life-limiting coexisting medical conditions, extrahepatic malignancy, active alcohol or substance abuse, active infection or uncontrolled sepsis, lack of psychosocial support or inability to comply with medical treatment)
- •Other malignancies either concomitant or within 5 years before liver transplantation
- •Patients not having received standard treatment for the primary CRC according to recommended guidelines
- •Prior extra hepatic metastatic disease or local relapse
- •Pregnancy at the time of inclusion
结局指标
主要结局
5 years overall survival (OS)
时间窗: 5 years
The evaluation of 5-years overall survival will be conducted by constructing survival curves using the Kaplan-Meier method. Graphs will be created following the best practices defined by Pocock. * If the proportionality of hazards is respected: Survival in each randomization arm will be compared using the Log-Rank test. The hazard ratio and the associated 95% confidence interval will be estimated using a Cox proportional hazards model. * If the proportionality of hazards is not respected: the difference in Restricted Mean Survival Time (RMST) between the arms and the associated 95% confidence interval will be estimated. The randomization stratification by cluster of centers will not be taken into account in the analyses. This is because it was done for administrative reasons.
次要结局
- 3-years overall survival (OS)(3 years)
- Disease free survival (DFS) (Arm LT+C) or Progression free survival (PFS) (Arm C)(3 and 5 years)
- Quality of life (QOL) of patients of Group LT followed by chemotherapy, using the NIDDK questionnaire of Liver Transplantation Database(year 5)
- Recurrence rate at 3 and 5 years(3 and 5 years)
- Quality of life (QOL) of patients using the European Organization for Research and Treatment of Cancer (EORTC) questionnaires.: QLQ-LMC21(year 5)
- Quality of life (QOL) of patients using the European Organization for Research and Treatment of Cancer (EORTC) questionnaires.: QLQ-C30(year 5)