Liver Transplant for Stable, Advanced Intrahepatic Cholangiocarcinoma
Primary Purpose
Cholangiocarcinoma, Intrahepatic
Status
Enrolling by invitation
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
Liver Transplantation
Sponsored by
About this trial
This is an interventional treatment trial for Cholangiocarcinoma, Intrahepatic
Eligibility 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)
Sites / Locations
- University Health Network
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
liver transplantation
Arm Description
Surgical Intervention - Liver transplantation
Outcomes
Primary Outcome Measures
patient survival
Secondary Outcome Measures
disease-free survival
patient survival
Full Information
NCT ID
NCT04195503
First Posted
December 9, 2019
Last Updated
July 24, 2023
Sponsor
University Health Network, Toronto
1. Study Identification
Unique Protocol Identification Number
NCT04195503
Brief Title
Liver Transplant for Stable, Advanced Intrahepatic Cholangiocarcinoma
Official Title
Liver Transplantation in Locally- Advanced, Unresectable, Non-Metastatic Intrahepatic Cholangiocarcinoma Treated With Neoadjuvant Systemic Therapy: A Single-centre, Pilot Study
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Enrolling by invitation
Study Start Date
December 10, 2019 (Actual)
Primary Completion Date
December 31, 2026 (Anticipated)
Study Completion Date
December 31, 2031 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Health Network, Toronto
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. 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.
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cholangiocarcinoma, Intrahepatic
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
liver transplantation
Arm Type
Other
Arm Description
Surgical Intervention - Liver transplantation
Intervention Type
Procedure
Intervention Name(s)
Liver Transplantation
Intervention Description
Surgical removal of liver containing tumor(s) and transplantation of new healthy liver graft
Primary Outcome Measure Information:
Title
patient survival
Time Frame
5 years
Secondary Outcome Measure Information:
Title
disease-free survival
Time Frame
5 years
Title
patient survival
Time Frame
1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gonzalo Sapisochin, MD
Organizational Affiliation
UHN
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Health Network
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2C4
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
29548617
Citation
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.
Results Reference
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Liver Transplant for Stable, Advanced Intrahepatic Cholangiocarcinoma
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