- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05175092
Living Donor Liver Transplantation for CRC Liver Metastases
Neo-adjuvant Chemotherapy Plus Living Donor Liver Transplantation (LDLT) for Non-Resectable Liver Metastases From Colorectal Cancer (CRC)
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Wisconsin
-
Madison, Wisconsin, United States, 53792
- University of Wisconsin School of Medicine and Public Health
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Intent to Treat: LDLT
Living Donor Liver Transplantation
|
The LDLT will be performed by the UW Division of Transplantation in accordance with the standard of care for this operation.
Other Names:
|
No Intervention: Control Group
Enrolled but does not receive LDLT
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Survival (OS)
Time Frame: 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.
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participants followed up to 5 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Disease Free Survival (DFS)
Time Frame: up to 5 years
|
DFS, defined as length of time after LDLT during which no disease is found according to RESIST v1.1 criteria.
|
up to 5 years
|
Site of Recurrence (Organs Affected)
Time Frame: up to 5 years
|
Patterns of recurrence will be investigated, assessed by standard of care chest, abdominal and pelvis imaging.
|
up to 5 years
|
Number of Sites of Recurrence per Participant
Time Frame: up to 5 years
|
Patterns of recurrence will be investigated, assessed by standard of care chest, abdominal and pelvis imaging.
|
up to 5 years
|
Survival Rate
Time Frame: up to 5 years
|
Surviving number of recipients who receive LDLT vs. control subjects will be assessed at 1-, 3-, and 5-years.
|
up to 5 years
|
Quality of Life Survey Score: EORTC QLQ-C30
Time Frame: 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.
|
up to 5 years
|
Quality of Life Survey Score: EORTC QLQ-LMC21
Time Frame: 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.
|
up to 5 years
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: David P Al-Adra, MD, PhD, University of Wisconsin, Madison
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- UW20113
- 2021-0021 (Other Identifier: HSIRB UW Madison)
- A539742 (Other Identifier: UW Madison)
- Protocol Version 7/15/2022 (Other Identifier: UW Madison)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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