Living Donor Liver Transplantation for CRC Liver Metastases
- Conditions
- Liver Metastasis Colon Cancer
- Interventions
- Procedure: Living Donor Liver Transplantation
- Registration Number
- NCT05175092
- Lead Sponsor
- University of Wisconsin, Madison
- 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.
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
Not provided
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Intent to Treat: LDLT Living Donor Liver Transplantation Living Donor Liver Transplantation
- Primary Outcome Measures
Name Time Method Overall Survival (OS) participants followed up to 5 years 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
Name Time Method Quality of Life Survey Score: EORTC QLQ-C30 up to 5 years 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.
Site of Recurrence (Organs Affected) up to 5 years Patterns of recurrence will be investigated, assessed by standard of care chest, abdominal and pelvis imaging.
Survival Rate up to 5 years Surviving number of recipients who receive LDLT vs. control subjects will be assessed at 1-, 3-, and 5-years.
Number of Sites of Recurrence per Participant up to 5 years Patterns of recurrence will be investigated, assessed by standard of care chest, abdominal and pelvis imaging.
Disease Free Survival (DFS) up to 5 years DFS, defined as length of time after LDLT during which no disease is found according to RESIST v1.1 criteria.
Quality of Life Survey Score: EORTC QLQ-LMC21 up to 5 years 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.
Trial Locations
- Locations (1)
University of Wisconsin School of Medicine and Public Health
🇺🇸Madison, Wisconsin, United States