Clinical trial NCT06986486: Liver Transplantation for Unresectable Perihilar Cholangiocarcinoma
Official title: Neoadjuvant Chemotherapy and Stereotactic Body Radiation Therapy Followed by Liver Transplantation for Unresectable Perihilar Cholangiocarcinoma: pCOLA
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Perihilar Cholangiocarcinoma
Klatskin Tumor
Keywords: liver transplantation
stereotactic body radiation therapy
downstaging
Lead sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Sponsor class: OTHER
First posted: 2025-05-23
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with liver-limited unresectable perihilar cholangiocarcinoma with no other non-oncological contraindication to liver transplantation

Brief summary: This is multicentric, single-arm, observational, investigator-drive study investigating the efficacy of liver transplantation after successful downstaging/disease control of unresectable perihilar cholangiocarcinoma using chemotherapy +/- immunotherapy and stereotactic body radiation therapy (SBRT).

Detailed description: Patients with unresectable pCCA who fit within inclusion criteria will be enrolled in the study. They will undergo staging laparoscopy with nodal sampling at the hepatic hilum. In case of negative staging (no peritoneal carcinomatosis, no positive hilar lymph nodes, negative peritoneal washing), they will receive downstaging with gemcitabine-cisplatin +/- durvalumab for 2 cycles, followed by SBRT, followed by at least 4 other cycles of gemcitabine-cisplatin +/- durvalumab. After downstaging, they will undergo disease restaging and, if at least disease stability is confirmed, they will undergo transplant screening and listing. Treatment with gemcitabine-cisplatin + durvalumab will continue until liver transplant, progression or unacceptable toxicity.

During listing, restaging will be performed every two months with CT scan and/or MRI, molecular markers and FDG-PET. The target interval between listing and transplant should be less than 90 days.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of unresectable peripheral cholangiocarcinoma arising one centimeter or more above the superior pancreatic margin, with tumor diameter ≤ 3 cm, diagnosed by:
* Transcatheter biopsy or brush cytology
* CA-19.9 \> 100 mg/ml and/or a mass on cross-sectional imaging with a malignant appearing stricture on cholangiography
* Biliary ploidy by FISH with a malignant appearing stricture on cholangiography
* Age between 18 years and 70 years
* Absence of intra- and extrahepatic metastases
* Absence of lymph-nodal metastases at any site
* Biliary stenting of all liver districts
* No contraindications to liver transplantation
* No concomitant malignancies or history of other malignancies in the previous 5 years
* Written informed consent

Exclusion Criteria:

* Intrahepatic cholangiocarcinoma
* Uncontrolled infection
* Concomitant malignancies or history of other malignancies in the previous 5 years

Primary outcomes:
measure: 3-year overall survival
timeFrame: 3 years
Secondary outcomes:
measure: 3-year recurrence-free survival
timeFrame: 3 years
measure: Safety and feasibility
timeFrame: 3 years
measure: Quality of life
timeFrame: 3 years
Other outcomes:
Locations:
city: Milan
country: Italy
facility: Fondazione IRCCS Istituto Nazionale Tumori di Milano
state: Michigan
Study officials:
References: