Liver Transplantation for Locally Advanced Intrahepatic Cholangiocarcinoma After SIRT and Chemotherapy

N/ANot Yet RecruitingNCT06910722

Assistance Publique - Hôpitaux de Paris36 enrolled

Overview

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.

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

Allocation

Purpose

HEALTH_SERVICES_RESEARCH

Masking

NONE

Enrollment

Conditions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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.

Time frame: 3 years post-transplant

Secondary Outcomes

Strategy feasibility 1/2

Number of patients benefiting from the complete strategy implemented

Time frame: 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

Time frame: 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.

Time frame: 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.

Time frame: 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;.

Time frame: 5 years after strategy implementation

oncological prognosis1/2

Number of patients not transplanted alive at 3 years (with or without recurrence)

Time frame: after 8 courses of chemotherapy

oncological prognosis 2/2

Time to onset, type and location of recurrence in transplanted and non-transplanted patients

Time frame: 5 years after strategy implementation

Histological response

Rate of tumor necrosis on total hepatectomy specimens in transplant patients

Time frame: 1 year after strategy implementation

Tolerance of neoadjuvant treatment

Number and type of adverse events induced by neoadjuvant therapy

Time frame: 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

Time frame: 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.

Time frame: from induction therapy until 3 months post-transplant