Clinical trial NCT06910722: Liver Transplantation for Locally Advanced Intrahepatic Cholangiocarcinoma After SIRT and Chemotherapy
Official title: Liver Transplantation for Locally Advanced Intrahepatic Cholangiocarcinoma After Selective Internal Radiotherapy With Labeled Yttrium and Chemotherapy: a Phase 2 Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Liver Transplantation in Locally Advanced Intrahepatic Cholangiocarcinoma
Keywords: liver transplantation
locally advanced intrahepatic cholangiocarcinoma
selective internal radiation therapy
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2025-04-04
Enrollment: 36
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: HEALTH_SERVICES_RESEARCH

Brief summary: The study hypothesis is that liver transplantation after selective internal radiation therapy (SIRT) and chemotherapy would improve 3-year overall survival in patients with locally advanced (unresectable but non-metastatic) intrahepatic cholangiocarcinoma.

It is planned to include 36 patients with locally advanced intrahepatic cholangiocarcinoma, not eligible for initial surgery and without metastases. Participants will be recruited from care facilities in France.

Detailed description: The hypothesis of the study is that liver transplantation after selective internal radiation therapy (SIRT) and chemotherapy would improve the overall 3-year survival of patients with locally advanced intrahepatic cholangiocarcinoma (unresectable but not metastatic).

All patients over 18 and under 65 years of age with histologically evidence, pauci-nodular (N≤5), locally advanced Intrahepatic cholangiocarcinoma (IHC) without extrahepatic involvement, considered technically unresectable by a panel of experts, eligible for treatment with SIRT, gemcitabine + cisplatin chemotherapy and Liver Transplant (LT).

Following treatment with SIRT + chemotherapy, tumor response or absence of tumor progression will be verified by a morphological workup combining CT-imaging, hepatic MRI and PET-CT.

After exploratory surgery to rule out any contraindications for LT, the patient will be list , with a minimum waiting of 3-month Follow-up will include assesment of Liver graft function, efficiency and tolerance of immunosuppressive therapy.

Eligibility criteria: Inclusion Criteria:

* Patient aged 18 to 65
* With histologically documented intrahepatic cholangiocarcinoma (primary diagnosis):

  * Uni or pauci nodular (≤ 5 lesions (all lesions are counted, even those less than 1 cm))
  * Without extrahepatic or lymph node involvement
  * Technically unresectable R0 according to an expert panel
* Tumor target \> 2 cm
* WHO 0-1
* free and informed consent signed
* highly effective contraception for men and women of childbearing age during study participation up to 2 years post TH

Exclusion Criteria:

* Extrahepatic, vesicular or perihilar cholangiocarcinoma
* Tumor infiltration of more than 50% of the liver
* Mixed cholangiocarcinoma, hepatocellular carcinoma, fibrolamellar carcinoma
* Previous treatment for CCI
* Cirrhosis ≥ Child B7
* Chronic alcoholism
* Uncontrolled chronic active infections (patients with HBV, HCV or HDV infections may be included if infections are controlled)
* Stage III A, IIIB, IV and V chronic renal failure (glomerular filtration rate 59 ml/min)
* Contraindications to liver transplant

  * Severe untreatable conditions
  * Recent history (less than 5 years) of cancer
  * severe comorbidities
  * Psychiatric or psychological disorders
* Pregnant or breast-feeding women
* Patient under guardianship
* Not affiliated to a Health care system
* Participating in another interventional study or within the exclusion period of a previous study involving the human body

Primary outcomes:
measure: Strategy efficacy : 3 years overall survival
timeFrame: 3 years post-transplant
Secondary outcomes:
measure: Strategy feasibility 1/2
timeFrame: Liver transplantation
measure: Strategy feasibility 2/2 contraindication to transplantation
timeFrame: Liver transplantation
measure: Associated factors with the 3-years overall survival
timeFrame: 3 years after strategy implementation
measure: therapeutic efficacy at 3 years
timeFrame: 3 years after strategy implementation
measure: therapeutic efficacy at 5 years
timeFrame: 5 years after strategy implementation
measure: oncological prognosis1/2
timeFrame: after 8 courses of chemotherapy
measure: oncological prognosis 2/2
timeFrame: 5 years after strategy implementation
measure: Histological response
timeFrame: 1 year after strategy implementation
measure: Tolerance of neoadjuvant treatment
timeFrame: after 8 courses of chemotherapy
measure: quality of life monitoring
timeFrame: from induction therapy until 5 years post-transplant
measure: Tolerance of global strategy
timeFrame: from induction therapy until 3 months post-transplant
Other outcomes:
Locations:
Study officials:
affiliation: APHP
name: Mohamed Bouattour
role: PRINCIPAL_INVESTIGATOR
References: