Liver Transplantation for Locally Advanced Intrahepatic Cholangiocarcinoma After SIRT and Chemotherapy (RIS-TH)

Liver Transplantation for Locally Advanced Intrahepatic Cholangiocarcinoma After Selective Internal Radiotherapy With Labeled Yttrium and Chemotherapy: a Phase 2 Study

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.

Study Overview

• Status: Recruiting
• Conditions: Intrahepatic Cholangiocarcinoma; Locally Advanced Intrahepatic Cholangiocarcinoma
• Intervention / Treatment: Procedure: Liver transplant

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.

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mohamed BOUATTOUR; Phone Number: +33 1.40.87.56.14; Email: mohamed.bouattour@aphp.fr

Study Locations

• France
  • Clichy-sous-Bois, France
    • Recruiting
    • BEAUJON
    • Contact: Mohamed BOUATTOUR; Email: mohamed.bouattour@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: liver transplant patients; Liver transplantation performed after selective internal radiotherapy (SIRT) with Yttrium-90 and chemotherapy in patients with locally advanced (unresectable but non-metastatic) intrahepatic cholangiocarcinoma.	Procedure: Liver transplant; follow-up of liver transplant patients after selective internal radiotherapy (SIRT) with Yttrium-90 and chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Strategy efficacy : 3 years overall survival	To assess the 3-year overall survival of patients undergoing liver transplantation for stable or downstaged locally advanced intrahepatic cholangiocarcinoma after induction treatment with selective internal radiotherapy and chemotherapy.	3 years post-transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Strategy feasibility 1/2	Number of patients benefiting from the complete strategy implemented	Liver transplantation
Strategy feasibility 2/2 contraindication to transplantation	Number of patients with radiological tumor progression according to RECIST 1.1 criteria after neoadjuvant treatment contraindicating transplantation	Liver transplantation
Associated factors with the 3-years overall survival	Socio-demographic and clinico-radio-biological characteristics at baseline and follow-up of living patients 3 years after strategy implementation.	3 years after strategy implementation
therapeutic efficacy at 3 years	Number of transplant patients alive and free of recurrence at 3 years after strategy implementation, as well as their socio-demographic and clinico-radiobiological characteristics at baseline and follow-up.	3 years after strategy implementation
therapeutic efficacy at 5 years	Number of transplanted patients alive 5 years after the strategy was implemented and number of transplanted patients alive and free of recurrence for the same period;.	5 years after strategy implementation
oncological prognosis1/2	Number of patients not transplanted alive at 3 years (with or without recurrence)	after 8 courses of chemotherapy
oncological prognosis 2/2	Time to onset, type and location of recurrence in transplanted and non-transplanted patients	5 years after strategy implementation
Histological response	Rate of tumor necrosis on total hepatectomy specimens in transplant patients	1 year after strategy implementation
Tolerance of neoadjuvant treatment	Number and type of adverse events induced by neoadjuvant therapy	after 8 courses of chemotherapy
quality of life monitoring	Changes in scores on the SF-36 quality-of-life questionnaire administered after neoadjuvant treatment prior to TH and then annually between the first and fifth years of follow-up	from induction therapy until 5 years post-transplant
Tolerance of global strategy	Number of adverse events of grade greater than or equal to 3 (NCI CTCAE) during neoadjuvant treatment + Number of severe complications greater than or equal to 3 of the Clavien-Dindo classification within 90 days of TH.	from induction therapy until 3 months post-transplant

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Mohamed Bouattour, APHP

Study record dates

Study Major Dates

• Study Start (Actual): August 28, 2025
• Primary Completion (Estimated): August 28, 2028
• Study Completion (Estimated): October 1, 2034

Study Registration Dates

• First Submitted: March 28, 2025
• First Submitted That Met QC Criteria: March 28, 2025
• First Posted (Actual): April 4, 2025

Study Record Updates

• Last Update Posted (Actual): April 6, 2026
• Last Update Submitted That Met QC Criteria: April 2, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: liver transplantation; selective internal radiation therapy; locally advanced intrahepatic cholangiocarcinoma
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Carcinoma; Cholangiocarcinoma; Therapeutics; Surgical Procedures, Operative; Transplantation; Digestive System Surgical Procedures; Cell- and Tissue-Based Therapy; Biological Therapy; Tissue Transplantation; Organ Transplantation; Liver Transplantation
• Other Study ID Numbers: APHP220677

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No