Neo-adjuvant Chemotherapy Plus Living Donor Liver Transplantation (LDLT) for Non-Resectable Liver Metastases From Colorectal Cancer (CRC)

  • STATUS
    Recruiting
  • End date
    Dec 19, 2030
  • participants needed
    50
  • sponsor
    University of Wisconsin, Madison
Updated on 19 October 2022

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.

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.

Details
Condition Liver Metastasis Colon Cancer
Treatment Living Donor Liver Transplantation, Living Donor Liver Transplantation
Clinical Study IdentifierNCT05175092
SponsorUniversity of Wisconsin, Madison
Last Modified on19 October 2022

Eligibility

Yes No Not Sure

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

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
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
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