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

September 28, 2023 updated by: Cristina Dopazo Taboada, Hospital Vall d'Hebron

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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 Type

Observational

Enrollment (Estimated)

34

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Spain
      • Barcelona, Spain, 08035
        • Recruiting
        • Department of HPB Surgery and Transplants, Hospital Vall d´Hebron
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 68 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study 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

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Study group
Patients with unresectable hilar cholangiocarcinoma (hCCA) ≤3cm in radial diameter, without evidence of lymph node or distant metastases
Drug: Neoadjuvant Chemo-radiotherapy
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Overall survival at 1, 3, and 5 years post-transplant
Time Frame: 5 years
5 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Recurrence free survival at 1, 3 and 5 years post-transplant
Time Frame: 5 years
5 years
Intention-to-treat survival of overall patients included in the study at 1,3 and 5 year
Time Frame: 5 years
5 years
The rate of patients included in the study who are finally transplanted.
Time Frame: 5 years
5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospital Vall d'Hebron

Investigators

  • Principal Investigator: Cristina Dopazo, HOSPITAL UNIVERSITARIO VALL D´HEBRON, UNIVERSIDAD AUTONOMA, BARCELONA
  • Principal Investigator: Ramón Charco-Torra, HOSPITAL UNIVERSITARIO VALL D´HEBRON, UNIVERSIDAD AUTONOMA, BARCELONA
  • Study Chair: Sonia Pascual-Bartolomé, HOSPITAL GENERAL UNIVERSITARIO, ALICANTE
  • Study Chair: Carmelo Loinaz-Segurola, Hospital Universitario 12 de Octubre, Madrid
  • Study Chair: José María Álamo-Martinez, Hospital Universitario Virgen del Rocío, Sevilla
  • Study Chair: José Luis Lucena de la Poza, Hospital Universitario Puerta de Hierro, Majadahonda
  • Study Chair: Arturo Colon-Rodríguez, HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARANON, MADRID
  • Study Chair: Diego López-Segarra, COMPLEJO HOSPITALARIO UNIVERSITARIO, BADAJOZ
  • Study Chair: Yilliam Fundora-Suárez, Hospital Clinic of Barcelona
  • Study Chair: Andrea Bosca-Robledo, Hospital Universitario La Fe
  • Study Chair: Juan Andrés Echeverri-Cifuentes, Hospital Universitario Marqués de Valdecilla, Santander
  • Study Chair: Josefina López-Domínguez, HOSPITAL UNIVERSITARIO DE BELLVITGE, BARCELONA
  • Study Chair: Xavier Merino-Casabiel, HOSPITAL UNIVERSITARIO VALL D´HEBRON, UNIVERSIDAD AUTONOMA, BARCELONA
  • Study Chair: David Leiva-Pedraza, HOSPITAL UNIVERSITARIO DE BELLVITGE, BARCELONA
  • Study Chair: María Teresa Salcedo-Allende, HOSPITAL UNIVERSITARIO VALL D´HEBRON, UNIVERSIDAD AUTONOMA, BARCELONA
  • Study Chair: José Antonio Gracia Solanas, HOSPITAL CLÍNICO UNIVERSITARIO LOZANO BLESA, ZARAGOZA
  • Study Chair: Manuel Angel Barrera-Gómez, HOSPITAL UNIVERSITARIO NUESTRA SEÑORA DE LA CANDELARIA, TENERIFE
  • Study Chair: Ricardo Robles-Campos, Hospital Universitario Virgen de la Arrixaca
  • Study Director: Laura Lladó-Garrida, HOSPITAL UNIVERSITARIO DE BELLVITGE, BARCELONA
  • Study Director: María Teresa Macarulla-Mercadé, HOSPITAL UNIVERSITARIO VALL D´HEBRON, UNIVERSIDAD AUTONOMA DE BARCELONA
  • Study Director: Begoña Navalpotro-Yagüe, HOSPITAL UNIVERSITARIO VALL D´HEBRON, UNIVERSIDAD AUTONOMA DE BARCELONA
  • Study Chair: Florian Castet, HOSPITAL UNIVERSITARIO VALL D´HEBRON, UNIVERSIDAD AUTONOMA DE BARCELONA
  • Study Chair: Julio Santoyo, Hospital Regional Universitario de Malaga
  • Study Chair: Manuel Durán Martínez, Hospital Universitario Reina Sofia de Cordoba
  • Study Chair: Natalia Zambudio, Hospital Virgen de las Nieves (Granada)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 24, 2020

Primary Completion (Estimated)

June 1, 2025

Study Completion (Estimated)

June 1, 2025

Study Registration Dates

First Submitted

May 4, 2020

First Submitted That Met QC Criteria

May 4, 2020

First Posted (Actual)

May 7, 2020

Study Record Updates

Last Update Posted (Actual)

September 29, 2023

Last Update Submitted That Met QC Criteria

September 28, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • hCCA-LT

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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