Trial | NCT04378023  Report issue

Official Title

Liver Transplant Combined With Neoadjuvant Chemo-radiotherapy in the Treatment of Unresectable Hilar Cholangiocarcinoma. A Prospective Multicenter Study.

  • Phase

    Phase 4

  • Study Type

    Observational [Patient Registry]

  • Status

    Recruiting

  • Study Participants

    34
A prospective multicentre study which includes patients ≤ 70 years-old diagnosed of unresectable hilar cholangiocarcinoma (hCCA) ≤3cm in radial diameter, without evidence of lymph node or distant metastases. Liver transplantation preceded by neoadjuvant radio-chemotherapy will be performed in this selected group.

The primary endpoint will be overall survival at 1, 3, and 5 years post-transplant. The secondary endpoints will be: 1) recurrence free survival at 1, 3 and 5 years post-transplant; 2) intention-to-treat survival of overall patients included in the study at 1,3 and 5 year; 3) the rate of patients included in the study who are finally transplanted.
A prospective multicentre pilot study which includes patients ≤ 70 years-old diagnosed of unresectable hilar cholangiocarcinoma (hCCA) ≤3cm in radial diameter, without evidence of lymph node or distant metastases.

The number of subjects necessary is 34 patients to achieve a power of 82% with a significance level of 0.05 to detect a 40% difference between the estimated 50% survival of those patients who are transplanted and 10% of those patients with hCCA unresectable who are not transplanted. This corresponds to a hazard ratio of 3.3219. Estimated loss to follow-up of 10% of patients.

RADIOLOGICAL EVALUATION

It will be considered unresectable those lesions Bismuth IV with the following criteria (Jarnagin WR, et al. Ann Surg 2001; 234:507; Memorial Sloan Kettering Cancer Center Hilar Cholangiocarcinoma Classification):

Bilateral extension to second order biliary
Unilateral extension to second-order biliary radicals AND contralateral portal vein involvement OR contralateral hepatic lobar atrophy
Main or bilateral portal vein involvement
Insufficient future liver remnant even after portal embolization

It will be performed the tumoral marker (CA 19.9), multiphase chest-abdomen CT scan, magnetic resonance cholangiopancreatography (MRCP) as well as positon emission tomography (PET)-scan if there is doubts of distant disease and upper endoscopic ultrasound (EUS) in order to rule out any obvious lymph node metastases. A biliary drainage will be placed by percutaneous transhepatic biliary drainage (PTBD) or endoscopic biliary drainage (EBD).

NEOADJUVANT TREATMENT

Patients will receive neoadjuvant radiotherapy (External - 50-54 grays) following by concomitant oral capecitabine (1,330mg/m2).Thereafter, gemcitabine iv (1000mg/m2) plus cisplatin iv will be administered the day 1 and 8 every 21 days until transplant.

A staging laparotomy/laparoscopy is recommended before including the patient in waiting list for transplant to confirm the abscence of extra-hepatic disease, especially peritoneal seeding and lymph nodes involvement.

A score exception will be allowed to optimized the treatment received and to be transplanted during the first 6 months.

LIVER TRANSPLANT AND FOLLOW UP

Regarding liver transplant technique, hepatic artery should be avoided for arterial reconstruction using the splenic artery or an iliac conduit.

Biomarker analyses in the explant specimen will be performed.

The patient will be monitored post-operatively at the clinical, biological and morphological levels every 3 months during the first 2 years and every 6 months thereafter in order to detect any recurrence and in the context of standard clinical care.
Study Started
Apr 24
2020
Primary Completion
Jun 01
2025
Anticipated
Study Completion
Jun 01
2025
Anticipated
Last Update
Sep 29
2023

Drug Neoadjuvant Chemo-radiotherapy [capecitabine (xeloda), gemcitabine (gemzar)]

Patients will receive neoadjuvant radiotherapy (External - 50-54 grays) following by concomitant oral capecitabine (825mg/m2 bid).Thereafter, gemcitabine iv (1000mg/m2) plus cisplatin iv (25mg/m2) will be administered the day 1 and 8 every 21 days until transplant.

Procedure Liver Transplantation

If no spread disease is discovered after neoadjuvant treatment, the patient will be listed for liver transplantation.

Study group None

Patients with unresectable hilar cholangiocarcinoma (hCCA) ≤3cm in radial diameter, without evidence of lymph node or distant metastases

Population

Those patients with unresectable malignant appearing hilar stricture and at least one of the following: Malignant cytology or histology CA 19.9>130U/mL without cholangits or/and jaundice Mass on cross-sectional imaging

Criteria 

Inclusion Criteria:

Willing and able to provide written consent form
Age ≤ 70 years-old
ECOG 0 or 1
Unresectable hCCA ≤3cm in radial diameter

Exclusion Criteria:

Those patients who have received chemotherapy or radiotherapy previously out of protocol
Liver, extrahepatic or lymph node metastases
Previous intent of surgical resection or percutaneous biopsy
Previous or concurrent cancer that is different in primary site or histology from adenocarcinoma, except cervical carcinoma in situ, localized prostate cancer, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis, T1). Any cancer curatively treated 5 years prior to entry is permitted.
Infection no controlled
No Results Posted