Clinical trial NCT02878473: Liver Transplantation for Early Intrahepatic Cholangiocarcinoma
Official title: Liver Transplantation for the Treatment of Early Stages of Intrahepatic Cholangiocarcinoma in Cirrhotics
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Intrahepatic Cholangiocarcinoma
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2016-08-25
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Diagnosis of intrahepatic cholangiocarcinoma (iCCA) is increasingly common in patients with liver cirrhosis, but these patients are denied liver transplantation (LT) by most centres due to historically poor results. Two retrospective evaluations have shown a 5 year survival \~65% in selected patients with an iCCA diagnosis at the pathology of the explanted liver. This suggests that LT can be a curative treatment if applied selectively. This study will evaluate the effectiveness of LT as a treatment for very early iCCA diagnosed in cirrhotic patients who meet the strict selection criteria. Patients with advanced cirrhosis (not candidates for resection) currently have no other curative treatment options. Participants will be allowed bridging therapies prior to receiving transplant. Participants will be followed for 5 years from the time of transplant with patient survival and disease recurrence as outcome measures.

Detailed description: Diagnosis of intrahepatic cholangiocarcinoma (iCCA) is increasingly common in patients with liver cirrhosis. iCCA is not an indication for Liver transplantation (LT) at most transplant centres given the historically poor rates of survival and high rates of disease recurrence. A recent retrospective study shows that patients found to have very early iCCA on explant after undergoing LT for another indication, had a 5 year survival of 65% and recurrence rate of 13%.This suggests that LT can be a curative treatment if applied selectively and that it is time to reevaluate LT as a treatment option for those with very early iCCA. This study will evaluate the effectiveness of LT as a treatment for very early iCCA diagnosed in cirrhotic patients. Diagnosis of iCCA will be based upon biopsy results of a new tumor which does not present radiologically as an HCC. Patients fulfilling the strict study selection criteria will undergo a full transplant assessment and must be deemed otherwise "suitable" for liver transplant as per their centre's criteria. Patients will be treated with bridging therapies while they are on the transplant waiting list according to each center's policy. Patients with disease progression (tumor \>3cm or development of extrahepatic disease) at any time prior to transplantation will be excluded. Participants will be followed for 5 years from the time of transplant with patient survival and disease recurrence as outcome measures.

Eligibility criteria: Inclusion Criteria:

* Eastern Cooperative Oncology Group: 0 or 1 at all times prior to Liver Transplantation
* Absence of cancer-related symptoms
* Liver cirrhosis (any etiology)
* Patient not eligible for liver resection due to poor liver function/portal hypertension
* Biopsy proven "very early" intrahepatic cholangiocarcinoma (iCCA)
* Willing and able to provide written informed consent.
* Negative serum pregnancy test for women of childbearing potential
* Biopsy proven "very early" (single ≤2 cm) iCCa
* No vascular or biliary involvement seen in preoperative imaging
* No extra-hepatic disease seen in preoperative imaging
* Carbohydrate Antigen (CA) 19.9 values are ≤100 ng/mL

Exclusion Criteria:

* Previous or concurrent cancer (with some exceptions)
* Patients that have had previous liver resection for iCCA and the current tumor is a recurrence.
* Progression of the tumor in size \>3 cm or development of extrahepatic disease.
* Large vessel invasion, defined radiologically.
* Renal dysfunction with an estimated creatinine clearance of less than 50 ml/min
* Pulmonary insufficiency
* History of cardiac disease:
* Uncontrolled infection(s)
* Known history of human immunodeficiency virus (HIV) infection.
* History of solid organ transplantation
* 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

Primary outcomes:
measure: 5 year patient survival
timeFrame: 5 years
Secondary outcomes:
measure: disease recurrence after liver transplantation
timeFrame: 5 years
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
Study officials:
affiliation: University Health Network, Toronto
name: Gonzalo Sapisochin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Clinic of Barcelona
name: Jordi Bruix, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sapisochin G, Facciuto M, Rubbia-Brandt L, Marti J, Mehta N, Yao FY, Vibert E, Cherqui D, Grant DR, Hernandez-Alejandro R, Dale CH, Cucchetti A, Pinna A, Hwang S, Lee SG, Agopian VG, Busuttil RW, Rizvi S, Heimbach JK, Montenovo M, Reyes J, Cesaretti M, Soubrane O, Reichman T, Seal J, Kim PT, Klintmalm G, Sposito C, Mazzaferro V, Dutkowski P, Clavien PA, Toso C, Majno P, Kneteman N, Saunders C, Bruix J; iCCA International Consortium. Liver transplantation for "very early" intrahepatic cholangiocarcinoma: International retrospective study supporting a prospective assessment. Hepatology. 2016 Oct;64(4):1178-88. doi: 10.1002/hep.28744. Epub 2016 Aug 24.