Living Donor Liver Transplantation for Unresectable Colorectal Cancer Liver Metastases

Titre officiel

Assessment of a Protocol Using a Combination of Neo-adjuvant Chemotherapy Plus Living Donor Liver Transplantation for Non-Resectable Liver Metastases From Colorectal Cancer

Sommaire:

Patients avec métastases hépatiques (MH) non résécables de cancer colorectal (CC) et au pronostic médiocre. La chirurgie offre une chance de survie distincte aux patients atteints de maladie résécable. Cette étude propose à certains patients avec métastases non résécables une transplantation hépatique avec un donneur vivant (THDV) 1) limitées au foie et 2) stables (sans progression) en chimiothérapie standard. Les participants potentiels seront soumis à une évaluation de la pertinence d'une greffe du foie à laquelle ils devront se présenter avec un donneur vivant volontaire. Ces participants subiront une THDV et feront l'objet d'un suivi de 5 ans portant sur la survie sans récidive et la qualité de vie comparées à celles d'un groupe témoin de participants sortis de l'étude avant la transplantation pour des raisons autres que la progression du cancer.

Description de l'essai

Primary Outcome:

• patient survival
• disease-free survival

Secondary Outcome:

• patterns of cancer recurrence after liver transplantation
• types of cancer recurrence treatments
• Number of participants that drop out of study prior to receiving intervention (transplantation surgery) due to chemotherapy-related adverse events, as assessed by CTCAE v4.0
• self-reported quality of life as assessed by EORTC QLQ-C30 questionnaire
• survival of intervention vs standard treatment
• patient survival
• patient survival
• disease-free survival
• disease-free survival

Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. Approximately half of all patients develop metastases, often to the liver or lung. Surgical treatment of liver metastases (LM) is the only curative treatment option; however, it has been estimated that only 20-40% of patients are candidates for liver resection. Surgery offers a distinct survival advantage: the 5-year survival after liver resection for LM is around 40-50% in most studies versus 10-20% 5-year survival for chemotherapy alone. In cases where the colorectal metastases are isolated to the liver but "unresectable", the total hepatectomy resulting from liver transplantation would remove all evident disease. CRC LM are considered an absolute contraindication for liver transplantation (LT) at most centres but recent reports of LT for colorectal LM from a single centre in Oslo, Norway demonstrated a 5-year survival of 56%. The Norway study was not stringent about inclusion criteria or pre-transplant chemotherapy, and transplanted patients whose tumours were actively growing. As a result many participants developed disease recurrence quite rapidly following transplant. The investigators hypothesize that tighter criteria would result in improved outcomes. Unfortunately, with a lack of deceased donor grafts for the investigators existing transplant patients, the investigators cannot utilize decease donor grafts for this study. Therefore the investigators will explore Living Donor Liver Transplantation (LDLT). Furthermore, LDLT is an elective surgery, allowing for more control over pre-transplant chemotherapy and tumour monitoring. This study will offer live donor liver transplantation (LDLT) to select patients with unresectable metastases that are 1) limited to the liver and 2) stable (non-progressing) on standard chemotherapy. Potential participants will be evaluated for liver transplant suitability and must also have a willing, healthy living donor come forward for evaluation. Those participants who undergo LDLT will be followed for survival, disease-free survival and quality of life for 5 years and compared to a "control group" of participants who drop out of study prior to transplantation due to reasons other than cancer progression.

Voir cet essai sur ClinicalTrials.gov