Liver Transplant for Stable, Advanced Intrahepatic Cholangiocarcinoma

• ClinicalTrials.gov Identifier: NCT04195503
• Recruitment Status: Enrolling by invitation
• First Posted: December 12, 2019
• Last Update Posted: July 25, 2023
• Sponsor: University Health Network, Toronto
• Information provided by (Responsible Party): University Health Network, Toronto

Study Description

Brief Summary:

Diagnosis of intrahepatic cholangiocarcinoma (iCCA) is an increasingly common form of primary liver cancer, but patients with this diagnosis are not currently eligible for LT. This study proposes to offer LT as an option to patients with advanced, unresectable iCCA who demonstrate at least 6 months of disease stability /regression while receiving standard chemotherapy. Patients will be referred and screened for study participation if they have achieved 6 months of disease stability.

They will be worked up for transplant and if eligible, will be listed. Disease must remain controlled while awaiting transplantation. After transplantation, patients will be followed for disease recurrence and overall survival, while receiving standard post-transplantation followup.

Condition or disease	Intervention/treatment	Phase
Cholangiocarcinoma, Intrahepatic	Procedure: Liver Transplantation	Not Applicable

Detailed Description:

Patients treated with standard of care chemotherapy for unresectable, biopsy-proven intrahepatic cholangiocarcinoma, and who demonstrate stability/regression of disease for a minimum of 6 months, may be eligible for study. Following informed consent and screening, eligible patients with a potential live liver donor (an interested, ABO-compatible individual, without obvious contraindications for donation) will be evaluated for transplantation. During this period, patients will continue to receive chemotherapy and imaging at the usual intervals. Once a patient completes the pre-transplant assessments and is deemed "suitable for transplantation" , the living donor's assessments may begin. If the donor is found suitable, a tentative date will be set for the surgeries. Systemic chemotherapy will be stopped approximately 4 weeks before the surgery date.

At that point, the potential recipient will be reimaged (CT scan). Test results, and inclusion and exclusion criteria will be reviewed to ensure the participant remains eligible to proceed to transplant. If these scans reveal any suspicion of tumor infiltration to surrounding tissues, an exploratory laparotomy or endoscopic ultrasound procedure will be scheduled to allow for visual examination and sampling of those tissues. Tissue samples, such as perihilar fat and/or lymph nodes, will be sent to the pathology department for urgent review. If extrahepatic disease is identified, the participant will be excluded from the study and the transplant will not be performed. Any excluded participants will continue to be followed for the study as "drop outs".

Otherwise, the donor and recipient surgeries will be performed in the standard fashion and with the preferred technique of the surgeon. The patient and donor will receive standard of care post-operative care.

Participants (recipients) will be monitored closely for evidence of tumor recurrence with imaging and blood tests. Results of these tests will be collected until completion of the study follow-up period (5-years after LT). In addition to tumor surveillance, liver transplant status will be assessed at each study timepoint (including graft loss, rejection, liver function tests, and details of immunosuppression). The study will also collect details of any biopsies performed, re-hospitalizations and surgical complications

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Liver Transplantation in Locally- Advanced, Unresectable, Non-Metastatic Intrahepatic Cholangiocarcinoma Treated With Neoadjuvant Systemic Therapy: A Single-centre, Pilot Study
• Actual Study Start Date: December 10, 2019
• Estimated Primary Completion Date: December 31, 2026
• Estimated Study Completion Date: December 31, 2031

Arms and Interventions

Arm	Intervention/treatment
liver transplantation; Surgical Intervention - Liver transplantation	Procedure: Liver Transplantation; Surgical removal of liver containing tumor(s) and transplantation of new healthy liver graft

Outcome Measures

Primary Outcome Measures :

1. patient survival [ Time Frame: 5 years ]

Secondary Outcome Measures :

1. disease-free survival [ Time Frame: 5 years ]
2. patient survival [ Time Frame: 1 year ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Male or female, aged 18 years or older, at time of consent
• Eastern Cooperative Oncology Group (ECOG) score : 0 or 1 at all times from study entry to LT
• Able and willing to provide written informed consent.
• Women of child-bearing potential must agree to use adequate birth control
• Histologically-confirmed diagnosis of iCCa
• Disease is deemed unresectable based on tumor location or underlying liver dysfunction
• No vascular invasion, extra-hepatic disease, or lymph node involvement detected on imaging
• Patients must have ≥ 6 months of disease stability or tumor regression on gemcitabine-based therapy. For patients who have progressed to second-line therapy, disease must also be controlled for ≥ 6 months on that regimen
• At least 1 living donor has stepped forward, is blood group compatible and has completed a "Health History form" which, upon review by the Living Donor team, is deemed acceptable and demonstrates no obvious contraindications to donation.

Exclusion Criteria:

• Previous or concurrent cancer (some exceptions permitted)
• Patients who have extrahepatic metastases, lymph node involvement, invasion or encasement of major hepatic vascular structures, perforation of the visceral peritoneum, invasion of extrahepatic structures, invasion of perihilar fat, periductular invasion, concurrent hepatoma or mixed hepatocellular cholangiocarcinoma
• Patients having received prior locoregional therapies or radiation to the tumor
• Renal dysfunction with an estimated creatinine clearance of less than 50 ml/min
• Known history of human immunodeficiency virus (HIV) infection.
• Prior history of solid organ or bone marrow transplantation
• Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
• Any condition that is unstable or which could jeopardize the safety of the patient and his/her compliance in the study
• Pregnant or breast-feeding patients (unless willing to abstain from breast-feeding)

Contacts and Locations

Locations

Canada, Ontario

University Health Network

Toronto, Ontario, Canada, M5G 2C4

Sponsors and Collaborators

University Health Network, Toronto

Investigators

• Principal Investigator: Gonzalo Sapisochin, MD; UHN

More Information

Publications:

Lunsford KE, Javle M, Heyne K, Shroff RT, Abdel-Wahab R, Gupta N, Mobley CM, Saharia A, Victor DW, Nguyen DT, Graviss EA, Kaseb AO, McFadden RS, Aloia TA, Conrad C, Li XC, Monsour HP, Gaber AO, Vauthey JN, Ghobrial RM; Methodist-MD Anderson Joint Cholangiocarcinoma Collaborative Committee (MMAJCCC). Liver transplantation for locally advanced intrahepatic cholangiocarcinoma treated with neoadjuvant therapy: a prospective case-series. Lancet Gastroenterol Hepatol. 2018 May;3(5):337-348. doi: 10.1016/S2468-1253(18)30045-1. Epub 2018 Mar 13. Erratum In: Lancet Gastroenterol Hepatol. 2018 Jun;3(6):e3.

• Responsible Party: University Health Network, Toronto
• ClinicalTrials.gov Identifier: NCT04195503
• Other Study ID Numbers: 19-5581
• First Posted: December 12, 2019
• Last Update Posted: July 25, 2023
• Last Verified: July 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Cholangiocarcinoma; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms