Description:
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.
Title
- Brief Title: 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
Clinical Trial IDs
- ORG STUDY ID:
15-9382-C
- NCT ID:
NCT02864485
Conditions
- Colorectal Cancer
- Liver Metastases
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
transplantation | Experimental | Live donor liver transplantation for the treatment of unresectable colorectal cancer liver metastases | |
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
Maximum Eligible Age: | 68 Years |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | patient survival |
Time Frame: | 5 years |
Safety Issue: | |
Description: | |
Secondary Outcome Measures
Measure: | patterns of cancer recurrence after liver transplantation |
Time Frame: | 5 years |
Safety Issue: | |
Description: | |
Measure: | types of cancer recurrence treatments |
Time Frame: | 5 years |
Safety Issue: | |
Description: | |
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 |
Time Frame: | prior to liver transplantation |
Safety Issue: | |
Description: | |
Measure: | self-reported quality of life as assessed by EORTC QLQ-C30 questionnaire |
Time Frame: | 6 month intervals for 5 years |
Safety Issue: | |
Description: | Compare the QoL of participants undergoing intervention vs participants that drop-out (for non cancer related reasons and are thereafter receiving palliative chemotherapy) |
Measure: | survival of intervention vs standard treatment |
Time Frame: | 1-, 3- and 5 years |
Safety Issue: | |
Description: | Compare the 1-, 3- and 5- year survival of patients that undergo intervention with those that drop-out of the study (due to non-cancer related reasons and receive standard chemotherapy) |
Measure: | patient survival |
Time Frame: | 1 year |
Safety Issue: | |
Description: | |
Measure: | patient survival |
Time Frame: | 3 years |
Safety Issue: | |
Description: | |
Measure: | disease-free survival |
Time Frame: | 1 year |
Safety Issue: | |
Description: | |
Measure: | disease-free survival |
Time Frame: | 3 years |
Safety Issue: | |
Description: | |
Details
Phase: | N/A |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | University Health Network, Toronto |
Trial Keywords
- Live donor liver transplantation
Last Updated
August 19, 2020