Colorectal Metastasis and Liver Transplantation With Organs From Deceased Donors

Study Overview
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Brief Summary
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MELODIC trial is an prospective, multicenter, non-randomized, open-label, parallel trial, aimed at assessing the efficacy (in terms of overall survival: OS) of liver transplantation (LT) in unresecable CRC liver-only metastases, compared with a matched cohort of patients bearing the same tumor characteristics, and treated with chemotherapy. Synthesis of Inclusion parameters: 10;10;10;100

Official Title
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Colorectal Metastasis and Liver Transplantation With Organs From Deceased Donors: an Inductive Padova Center Protocol

Conditions
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Colorectal Liver Metastases, Colorectal Adenocarcinoma, Unresectable Malignant Neoplasm

Intervention / Treatment
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* Procedure: Liver Transplant
* Drug: Chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (Sythesis: 10;10;10;100): ≥ 18 and <70 years Performance status, ECOG 0-1 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 tumor Liver metastases not eligible for curative liver resection confirmed by the validation committee At least one line (3 months) of chemotherapy No signs of extra hepatic metastatic disease or local recurrence on CT, MRI and Pet-CT within 4 weeks prior to the faculty meeting at the transplant unit Before start of chemotherapy no lesion should be larger than > 10 cm Objective response according to RECIST 1.1 or SD at two consecutive CT without CEA increase Patient with less than 10% response on chemotherapy may be included if they obtain al least 20% response after TACE (DEB-IRI) or by 90Y-spheres At least 10 months time span from CRC resection and date of being listed on the transplantation list. Satisfactory blood tests Hb >10g/dL, neutrophils >1.0, Bilirubin<2 x upper normal level, AST, ALT<5 x upper normal level, creatinine and albumin in normal level. CEA<100 ng/ml Signed informed consent and expected cooperation of the patients for the treatment and follow up Exclusion Criteria: Weight loss >10% the last 6 months Patient BMI > 30 Participation refusal General contraindication to LT Prior extra hepatic metastatic disease or primary tumor local relapse. Other malignancies in the previous 5 years Pregnancy or breast feeding Any reason why, in the opinion of the investigator, the patient should not participate.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The study will compared survival in patient enrolled in the MELODIC trial with the OS in a matched cohort of patients treated with chemotherapy
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study arm<br>Liver transplant | Procedure: Liver Transplant<br>* Liver Transplant from cadaveric donors<br>|
| Other: Parallel arm<br>Chemotherapy | Drug: Chemotherapy<br>* Chemotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | 3 years | 
| Overall survival |  | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival |  | 3 and 5 years | 
| Proportion of drop out |  | within liver transplant | 
| Complication rate |  | 90 days after liver transplant |