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Living Donor Liver Transplantation for CRC Liver Metastases

Primary Purpose

Liver Metastasis Colon Cancer

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Living Donor Liver Transplantation
Sponsored by
University of Wisconsin, Madison
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Liver Metastasis Colon Cancer focused on measuring living donor liver transplant

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Recipient Inclusion Criteria

In order to be eligible to participate in this study, a potential recipient must meet all of the following criteria prior to transplant procedure:

  • General 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
  • Cancer-related inclusion criteria:

    • 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 CEA level >80 μg/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 RECIST v 1.1 criteria
      • The only site of metastases is the liver (Staging CT scans are clear of metastases)
  • Transplant related inclusion criteria:

    • 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

Recipient Exclusion Criteria:

A potential recipient who meets any of the following criteria will be excluded from participation in this study:

  • General 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
  • Cancer-related exclusion criteria:

    • 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 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
  • Transplant-related exclusion criteria:

    • Renal dysfunction with an estimated creatinine clearance of less than 50 ml/min
    • Pulmonary insufficiency (history of chronic obstructive pulmonary disease and FEV1 /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

Donor eligibility criteria:

In order to be eligible to participate in this study, a potential donor must meet all of the following criteria prior to transplant procedure:

  • Willing and able to provide informed consent
  • Upon review by the Living Donor team, is deemed acceptable and demonstrates no obvious contraindications to donation
  • Not an altruistic donor
  • Before transplant surgery, must be approved as a liver donor by UW Health Transplant Program

Sites / Locations

  • University of Wisconsin School of Medicine and Public HealthRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Intent to Treat: LDLT

Control Group

Arm Description

Living Donor Liver Transplantation

Enrolled but does not receive LDLT

Outcomes

Primary Outcome Measures

Overall Survival (OS)
Overall survival, defined as length of time from the start of (neoadjuvant) chemotherapy that subjects diagnosed with colorectal liver metastases are still alive.

Secondary Outcome Measures

Disease Free Survival (DFS)
DFS, defined as length of time after LDLT during which no disease is found according to RESIST v1.1 criteria.
Site of Recurrence (Organs Affected)
Patterns of recurrence will be investigated, assessed by standard of care chest, abdominal and pelvis imaging.
Number of Sites of Recurrence per Participant
Patterns of recurrence will be investigated, assessed by standard of care chest, abdominal and pelvis imaging.
Survival Rate
Surviving number of recipients who receive LDLT vs. control subjects will be assessed at 1-, 3-, and 5-years.
Quality of Life Survey Score: EORTC QLQ-C30
Quality of life is measured at 1-, 3-, and 5-years using the EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire). The questionnaire assesses multi-item scales, each item scoring from 1 to 4, with higher scores representing a higher level of symptomatology or problems.
Quality of Life Survey Score: EORTC QLQ-LMC21
Quality of life is measured at 1-, 3-, and 5-years using the EORTC QLQ-LMC21 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire). The questionnaire assesses multi-item scales, each item scoring from 1 to 4, with higher scores representing a higher level of symptomatology or problems.

Full Information

First Posted
December 13, 2021
Last Updated
September 27, 2023
Sponsor
University of Wisconsin, Madison
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1. Study Identification

Unique Protocol Identification Number
NCT05175092
Brief Title
Living Donor Liver Transplantation for CRC Liver Metastases
Official Title
Neo-adjuvant Chemotherapy Plus Living Donor Liver Transplantation (LDLT) for Non-Resectable Liver Metastases From Colorectal Cancer (CRC)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 2023 (Anticipated)
Primary Completion Date
December 2030 (Anticipated)
Study Completion Date
December 2030 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Wisconsin, Madison

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study will test the safety and efficacy of living donor liver transplant after standard-of-care chemotherapy for participants with non-resectable liver metastases (LM) from colorectal cancer. 25 donor-recipient pairs will be enrolled (50 participants). Donors will be on study for 2 years and recipients will be on study for up to 5 years.
Detailed Description
This study is a single center, open-label study available to male and female adults with CRC LM that are deemed to be "unresectable" and who are receiving standard of care chemotherapy. Participants will be worked up for LDLT while continuing to receive chemotherapy and, if deemed eligible for surgery, will stop chemotherapy 4 weeks prior to receiving a living donor transplant. Recipients will be followed for 5 years (for safety, survival and disease recurrence for purposes of study data collection). They will continue to be monitored for safety, survival and disease recurrence indefinitely as part of University of Wisconsin (UW) Health's Organ Transplant Program care standards. Living liver donors will be followed for 2 years after transplant surgery for safety monitoring as part of this study. Recruitment will be done in two stages. The first stage will be a pilot study of 5 recipients to determine if LDLT is a suitable treatment for patients with non-resectable LM. If, after 3 years of follow-up, the overall survival is greater than 60%, stage two recruitment will commence. Thus, an interim analysis will be done for the first 5 recipients prior to requiring a larger number of subjects. Stage two recruitment will focus on accruing a total of up to 20 additional recipients to be analyzed. The control group will consist of any potential recipients that sign the informed consent and are enrolled in the study but do not undergo LDLT due to a lack of an eligible donor. These participants will be referred back to their medical oncologists to receive standard of care chemotherapy, and will continue to be followed as the control group. Patients who sign the informed consent and are enrolled in the study with an eligible live donor but do not undergo LDLT due to disease progression or a contraindication is established for undergoing LT (exclusion criteria) will also be referred back to their medical oncologists to receive standard of care chemotherapy. This group will be followed as part of the intent to treat cohort.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Liver Metastasis Colon Cancer
Keywords
living donor liver transplant

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
single-center, open-label, two-stage recruitment pilot study of 5 recipients to determine if LDLT is a suitable treatment for patients with non-resectable LM with 3 years of follow-up, if Overall Survival greater than 60%, then stage two recruitment focusing on accruing additional recipients will commence. control group of participants that sign the informed consent and are enrolled in the study but do not undergo LDLT due to a lack of an eligible donor
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Intent to Treat: LDLT
Arm Type
Experimental
Arm Description
Living Donor Liver Transplantation
Arm Title
Control Group
Arm Type
No Intervention
Arm Description
Enrolled but does not receive LDLT
Intervention Type
Procedure
Intervention Name(s)
Living Donor Liver Transplantation
Other Intervention Name(s)
LDLT
Intervention Description
The LDLT will be performed by the UW Division of Transplantation in accordance with the standard of care for this operation.
Primary Outcome Measure Information:
Title
Overall Survival (OS)
Description
Overall survival, defined as length of time from the start of (neoadjuvant) chemotherapy that subjects diagnosed with colorectal liver metastases are still alive.
Time Frame
participants followed up to 5 years
Secondary Outcome Measure Information:
Title
Disease Free Survival (DFS)
Description
DFS, defined as length of time after LDLT during which no disease is found according to RESIST v1.1 criteria.
Time Frame
up to 5 years
Title
Site of Recurrence (Organs Affected)
Description
Patterns of recurrence will be investigated, assessed by standard of care chest, abdominal and pelvis imaging.
Time Frame
up to 5 years
Title
Number of Sites of Recurrence per Participant
Description
Patterns of recurrence will be investigated, assessed by standard of care chest, abdominal and pelvis imaging.
Time Frame
up to 5 years
Title
Survival Rate
Description
Surviving number of recipients who receive LDLT vs. control subjects will be assessed at 1-, 3-, and 5-years.
Time Frame
up to 5 years
Title
Quality of Life Survey Score: EORTC QLQ-C30
Description
Quality of life is measured at 1-, 3-, and 5-years using the EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire). The questionnaire assesses multi-item scales, each item scoring from 1 to 4, with higher scores representing a higher level of symptomatology or problems.
Time Frame
up to 5 years
Title
Quality of Life Survey Score: EORTC QLQ-LMC21
Description
Quality of life is measured at 1-, 3-, and 5-years using the EORTC QLQ-LMC21 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire). The questionnaire assesses multi-item scales, each item scoring from 1 to 4, with higher scores representing a higher level of symptomatology or problems.
Time Frame
up to 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Recipient Inclusion Criteria In order to be eligible to participate in this study, a potential recipient must meet all of the following criteria prior to transplant procedure: General 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 Cancer-related inclusion criteria: 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 CEA level >80 μg/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 RECIST v 1.1 criteria The only site of metastases is the liver (Staging CT scans are clear of metastases) Transplant related inclusion criteria: 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 Recipient Exclusion Criteria: A potential recipient who meets any of the following criteria will be excluded from participation in this study: General 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 Cancer-related exclusion criteria: 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 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 Transplant-related exclusion criteria: Renal dysfunction with an estimated creatinine clearance of less than 50 ml/min Pulmonary insufficiency (history of chronic obstructive pulmonary disease and FEV1 /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 Donor eligibility criteria: In order to be eligible to participate in this study, a potential donor must meet all of the following criteria prior to transplant procedure: Willing and able to provide informed consent Upon review by the Living Donor team, is deemed acceptable and demonstrates no obvious contraindications to donation Not an altruistic donor Before transplant surgery, must be approved as a liver donor by UW Health Transplant Program
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Cancer Connect
Phone
800-622-8922
Email
clinicaltrials@cancer.wisc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David P Al-Adra, MD, PhD
Organizational Affiliation
University of Wisconsin, Madison
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Wisconsin School of Medicine and Public Health
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cancer Connect
Phone
800-622-8922
Email
clinicaltrials@cancer.wisc.edu

12. IPD Sharing Statement

Plan to Share IPD
No

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Living Donor Liver Transplantation for CRC Liver Metastases

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