Liver Metastasis Colon Cancer
Conditions
Keywords
living donor liver transplant
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.
Interventions
PROCEDURELiving Donor Liver Transplantation
The LDLT will be performed by the UW Division of Transplantation in accordance with the standard of care for this operation.
Sponsors
University of Wisconsin, Madison
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention 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
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORDavid P Al-Adra, MD, PhD
University of Wisconsin, Madison
Outcome results
None listed