Living Donor Liver Transplantation for Unresectable Colorectal Cancer Liver Metastases
Primary Purpose
Colorectal Cancer, Liver Metastases
Status
Recruiting
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
live donor liver transplantation
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Cancer focused on measuring Live donor liver transplantation
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
Sites / Locations
- Toronto General HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
transplantation
Arm Description
Live donor liver transplantation for the treatment of unresectable colorectal cancer liver metastases
Outcomes
Primary Outcome Measures
patient survival
disease-free survival
Secondary Outcome Measures
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
Compare the QoL of participants undergoing intervention vs participants that drop-out (for non cancer related reasons and are thereafter receiving palliative chemotherapy)
survival of intervention vs standard treatment
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)
patient survival
patient survival
disease-free survival
disease-free survival
Full Information
NCT ID
NCT02864485
First Posted
August 4, 2016
Last Updated
May 12, 2023
Sponsor
University Health Network, Toronto
1. Study Identification
Unique Protocol Identification Number
NCT02864485
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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 3, 2016 (Actual)
Primary Completion Date
September 2025 (Anticipated)
Study Completion Date
December 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Health Network, Toronto
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer, Liver Metastases
Keywords
Live donor liver transplantation
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
transplantation
Arm Type
Experimental
Arm Description
Live donor liver transplantation for the treatment of unresectable colorectal cancer liver metastases
Intervention Type
Procedure
Intervention Name(s)
live donor liver transplantation
Intervention Description
live donor liver transplantation
Primary Outcome Measure Information:
Title
patient survival
Time Frame
5 years
Title
disease-free survival
Time Frame
5 years
Secondary Outcome Measure Information:
Title
patterns of cancer recurrence after liver transplantation
Time Frame
5 years
Title
types of cancer recurrence treatments
Time Frame
5 years
Title
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
Title
self-reported quality of life as assessed by EORTC QLQ-C30 questionnaire
Description
Compare the QoL of participants undergoing intervention vs participants that drop-out (for non cancer related reasons and are thereafter receiving palliative chemotherapy)
Time Frame
6 month intervals for 5 years
Title
survival of intervention vs standard treatment
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)
Time Frame
1-, 3- and 5 years
Title
patient survival
Time Frame
1 year
Title
patient survival
Time Frame
3 years
Title
disease-free survival
Time Frame
1 year
Title
disease-free survival
Time Frame
3 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
68 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Erin Winter, BSc
Phone
416-340-4800
Ext
6093
Email
erin.winter@uhn.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gonzalo Sapisochin, MD
Organizational Affiliation
University Health Network, Toronto
Official's Role
Principal Investigator
Facility Information:
Facility Name
Toronto General Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2N2
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Erin Winter
Phone
416-340-4800
Ext
6093
Email
erin.winter@uhn.ca
12. IPD Sharing Statement
Learn more about this trial
Living Donor Liver Transplantation for Unresectable Colorectal Cancer Liver Metastases
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