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Living Donor Liver Transplantation for Unresectable Colorectal Cancer Liver Metastases

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02864485
Recruitment Status : Recruiting
First Posted : August 12, 2016
Last Update Posted : May 15, 2023
Sponsor:
Information provided by (Responsible Party):
University Health Network, Toronto

Tracking Information
First Submitted Date  ICMJE August 4, 2016
First Posted Date  ICMJE August 12, 2016
Last Update Posted Date May 15, 2023
Actual Study Start Date  ICMJE August 3, 2016
Estimated Primary Completion Date September 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 11, 2016)
  • patient survival [ Time Frame: 5 years ]
  • disease-free survival [ Time Frame: 5 years ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 11, 2016)
  • patterns of cancer recurrence after liver transplantation [ Time Frame: 5 years ]
  • types of cancer recurrence treatments [ Time Frame: 5 years ]
  • 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 ]
  • self-reported quality of life as assessed by EORTC QLQ-C30 questionnaire [ Time Frame: 6 month intervals for 5 years ]
    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 [ Time Frame: 1-, 3- and 5 years ]
    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 [ Time Frame: 1 year ]
  • patient survival [ Time Frame: 3 years ]
  • disease-free survival [ Time Frame: 1 year ]
  • disease-free survival [ Time Frame: 3 years ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Living Donor Liver Transplantation for Unresectable Colorectal Cancer Liver Metastases
Official Title  ICMJE Assessment of a Protocol Using a Combination of Neo-adjuvant Chemotherapy Plus Living Donor Liver Transplantation for Non-Resectable Liver Metastases From Colorectal Cancer
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Colorectal Cancer
  • Liver Metastases
Intervention  ICMJE Procedure: live donor liver transplantation
live donor liver transplantation
Study Arms  ICMJE Experimental: transplantation
Live donor liver transplantation for the treatment of unresectable colorectal cancer liver metastases
Intervention: Procedure: live donor liver transplantation
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 11, 2016)		 20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2025
Estimated Primary Completion Date September 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 68 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Erin Winter, BSc 416-340-4800 ext 6093 erin.winter@uhn.ca
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02864485
Other Study ID Numbers  ICMJE 15-9382-C
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party University Health Network, Toronto
Original Responsible Party Same as current
Current Study Sponsor  ICMJE University Health Network, Toronto
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Gonzalo Sapisochin, MD University Health Network, Toronto
PRS Account University Health Network, Toronto
Verification Date May 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP