Clinical trial NCT02864485: Living Donor Liver Transplantation for Unresectable Colorectal Cancer Liver Metastases
Official title: Assessment of a Protocol Using a Combination of Neo-adjuvant Chemotherapy Plus Living Donor Liver Transplantation for Non-Resectable Liver Metastases From Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Colorectal Cancer
Liver Metastases
Keywords: Live donor liver transplantation
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2016-08-12
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 68
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Patients with unresectable liver metastases (LM) from colorectal cancer (CRC)have a poor prognosis. In patients with resectable disease, surgery offers a distinct survival benefit. 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.

Detailed description: 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 centers but recent reports of LT for colorectal LM from a single center 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 tumors 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 tumor 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.

Eligibility criteria: Inclusion Criteria:

* Must reside in Canada
* ECOG ( Eastern Cooperative Oncology Group) score : 0-1 at all times prior to LDLT (excursions to ECOG 2 allowed at investigator's discretion)
* Proven colorectal Liver Metastases (LM).
* Willing and able to provide written informed consent.
* Negative serum pregnancy test for women of childbearing potential
* Both men and women must agree to use adequate barrier birth control measures during the course of the trial.
* At least 1 "acceptable", ABO-compatible living donor has stepped forward
* Primary Colorectal cancer tumor stage is ≤T4a
* Time from primary CRC resection to transplant is ≥6 months
* Bilateral and non-resectable LM
* No major vascular invasion by LM; metastases isolated to liver
* The patient has undergone systemic chemotherapy (eg. FOLFOX +/- bevacizumab or FOLFIRI +/- bevacizumab) for ≥3 months
* demonstrated stability or regression of LM over at minimum the 3 months preceding screening
* Carcinoembryonic Antigen (CEA) values are stable or decreasing at all timepoints prior to the transplant surgery.

Exclusion Criteria:

* Previous or concurrent cancer (with some exceptions)
* prior lung resection
* Progression of LM at any timepoint prior to transplant surgery
* Renal dysfunction with an estimated creatinine clearance of less than 50 ml/min
* Pulmonary insufficiency
* History of cardiac disease
* Known history of human immunodeficiency virus (HIV) infection or chronic hepatitis B and/or C infection.
* Patients with debilitating neuropathy. (CTCAE \> grade 2)
* BRAF + tumors
* Any condition that is unstable or which could jeopardize the safety of the patient and his/her compliance in the study

Primary outcomes:
measure: patient survival
timeFrame: 5 years
measure: disease-free survival
timeFrame: 5 years
Secondary outcomes:
measure: patterns of cancer recurrence after liver transplantation
timeFrame: 5 years
measure: types of cancer recurrence treatments
timeFrame: 5 years
measure: 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
timeFrame: prior to liver transplantation
measure: self-reported quality of life as assessed by EORTC QLQ-C30 questionnaire
timeFrame: 6 month intervals for 5 years
measure: survival of intervention vs standard treatment
timeFrame: 1-, 3- and 5 years
measure: patient survival
timeFrame: 1 year
measure: patient survival
timeFrame: 3 years
measure: disease-free survival
timeFrame: 1 year
measure: disease-free survival
timeFrame: 3 years
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
Study officials:
affiliation: University Health Network, Toronto
name: Gonzalo Sapisochin, MD
role: PRINCIPAL_INVESTIGATOR
References: