Neo-Adjuvant Chemotherapy Plus Living Donor Liver Transplantation for the Treatment of Non-Resectable Liver Metastases from Colorectal Cancer

Inclusion Criteria

• Male or female, aged 18 - 65 years old inclusive, at study entry
• Willing and able to provide written informed consent
• Reside in the United States
• Negative serum pregnancy test for women of childbearing potential
• Eastern Cooperative Oncology Group (ECOG) : 0 or 1 at all times prior to LDLT
• Biopsy-proven colorectal LM
• Tumor must have the following characteristics * Non-resectable LM (by consensus of three hepatobiliary [HPB] surgeons). All potential recipients will be presented at Multidisciplinary Tumor Rounds for discussion of treatment options * Synchronous or Metachronous disease * R0 resection can be achieved by total hepatectomy * Primary CRC tumor stage is =< T3 and =< N2 * Oslo score of 0-1. The Oslo Score summarizes 4 negative predictive factors for overall survival after liver transplantation for CRLM where each factor is assigned 1 point; maximal diameter of the largest lesion > 5.5 cm, pre transplant carcinoembryonic antigen (CEA) level > 80 ug/L, progressive disease at time of liver transplant and interval from diagnosis to transplant < 2 years * The patient has undergone first-line “standard of care” chemotherapy for a minimum of 3 months (at the time of screening), with demonstrated stability or regression of LM based on Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 criteria * The only site of metastases is the liver (Staging computed tomography [CT] scans are clear of metastases)
• At least one ABO compatible living donor has been identified, and has completed an intake history which, upon review by the Living Donor team, is deemed acceptable and demonstrates no obvious contraindications to donation (Altruistic donors will not be accepted for the study).
• Complete colonoscopy within the 12 months prior to potential recipient’s inclusion, showing no signs of local recurrence
• Prior authorization by private insurance as a single payer exception is required. This will be discussed on a case-by-case basis with the insurance providers and the Transplant Financial Group
• Creatinine clearance greater than or equal to 50 ml/min
• Absolute neutrophil count greater than or equal to 1,500/uL
• Child-Pugh score of A
• Meets criteria to undergo a liver transplantation (UConnect documents: IP - Liver Transplant - Adult – Evaluation, Cardiac Assessment of Liver Transplant Candidates - Adult - Inpatient/Ambulatory)
• DONOR: Willing and able to provide informed consent
• DONOR: Upon review by the Living Donor team, is deemed acceptable and demonstrates no obvious contraindications to donation
• DONOR: Not an altruistic donor
• DONOR: Before transplant surgery, must be approved as a liver donor by University of Wisconsin (UW) Health Transplant Program

Exclusion Criteria

• Substance abuse, medical, psychological or social conditions that may interfere with the potential recipient’s participation in the study or evaluation of the study results
• Known or suspected allergy to any agent given in association with this trial
• Any condition that is unstable or which could jeopardize the safety of the potential recipient and his/her compliance in the study
• Pregnant or breast-feeding patients
• Previous or concurrent cancer that is distinct in primary site or histology from adenocarcinoma, except ductal carcinoma in situ, cervical carcinoma in situ, localized prostate cancer, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis & T1). Any cancer curatively treated 5 years prior to entry is permitted
• Progression of LM at any time point prior to transplant surgery
• LM show no major vascular invasion: no vena cava involvement and no porta hepatis involvement as seen on scans (including positron emission tomography [PET]-CT), or through endoscopic ultrasound and exploratory laparotomy sampling of porta hepatis lymph nodes
• BRAF+ mutation or microsatellite instability of either primary tumor or LM
• Renal dysfunction with an estimated creatinine clearance of less than 50 ml/min
• Pulmonary insufficiency (history of chronic obstructive pulmonary disease and forced expiratory volume [FEV1] /forced vital capacity[FVC] < 75%)
• History of cardiac disease: *Congestive heart failure > New York Heart Association (NYHA) class 2 *Non-revascularized coronary artery disease *Uncontrolled hypertension (two systolic blood pressure readings greater than 150 in past 2 visits)
• Uncontrolled infection(s) as defined per surgeon, subject may be on antibiotics at time of transplant
• Severe liver dysfunction (Child-Pugh Score of B or C will be excluded)
• History of solid organ transplantation