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

NCT ID: NCT04378023

Last Updated: 2025-09-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

34 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-04-24

Study Completion Date

2027-06-01

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Unresectable Cholangiocarcinoma

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Study group

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

Neoadjuvant Chemo-radiotherapy

Intervention Type DRUG

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.

Liver Transplantation

Intervention Type PROCEDURE

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

Interventions

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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.

Intervention Type DRUG

Liver Transplantation

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

Intervention Type PROCEDURE

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hospital Vall d'Hebron

OTHER

Sponsor Role lead

Responsible Party

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Cristina Dopazo Taboada

Consultant Surgeon

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Cristina Dopazo

Role: PRINCIPAL_INVESTIGATOR

HOSPITAL UNIVERSITARIO VALL D´HEBRON, UNIVERSIDAD AUTONOMA, BARCELONA

Ramón Charco-Torra

Role: PRINCIPAL_INVESTIGATOR

HOSPITAL UNIVERSITARIO VALL D´HEBRON, UNIVERSIDAD AUTONOMA, BARCELONA

Sonia Pascual-Bartolomé

Role: STUDY_CHAIR

HOSPITAL GENERAL UNIVERSITARIO, ALICANTE

Carmelo Loinaz-Segurola

Role: STUDY_CHAIR

HOSPITAL UNIVERSITARIO 12 DE OCTUBRE, MADRID

José María Álamo-Martinez

Role: STUDY_CHAIR

HOSPITAL UNIVERSITARIO VIRGEN DEL ROCIO, SEVILLA

José Luis Lucena de la Poza

Role: STUDY_CHAIR

HOSPITAL UNIVERSITARIO PUERTA DE HIERRO, MAJADAHONDA

Arturo Colon-Rodríguez

Role: STUDY_CHAIR

HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARANON, MADRID

Diego López-Segarra

Role: STUDY_CHAIR

COMPLEJO HOSPITALARIO UNIVERSITARIO, BADAJOZ

Yilliam Fundora-Suárez

Role: STUDY_CHAIR

Hospital Clinic of Barcelona

Andrea Bosca-Robledo

Role: STUDY_CHAIR

Hospital Universitario La Fe

Juan Andrés Echeverri-Cifuentes

Role: STUDY_CHAIR

HOSPITAL UNIVERSITARIO MARQUES DE VALDECILLA, SANTANDER

Marina Vila-Tura

Role: STUDY_CHAIR

HOSPITAL UNIVERSITARIO DE BELLVITGE, BARCELONA

Xavier Merino-Casabiel

Role: STUDY_CHAIR

HOSPITAL UNIVERSITARIO VALL D´HEBRON, UNIVERSIDAD AUTONOMA, BARCELONA

David Leiva-Pedraza

Role: STUDY_CHAIR

HOSPITAL UNIVERSITARIO DE BELLVITGE, BARCELONA

María Teresa Salcedo-Allende

Role: STUDY_CHAIR

HOSPITAL UNIVERSITARIO VALL D´HEBRON, UNIVERSIDAD AUTONOMA, BARCELONA

José Antonio Gracia Solanas

Role: STUDY_CHAIR

HOSPITAL CLÍNICO UNIVERSITARIO LOZANO BLESA, ZARAGOZA

Manuel Angel Barrera-Gómez

Role: STUDY_CHAIR

HOSPITAL UNIVERSITARIO NUESTRA SEÑORA DE LA CANDELARIA, TENERIFE

Ricardo Robles-Campos

Role: STUDY_CHAIR

Hospital Universitario Virgen de la Arrixaca

Laura Lladó-Garrida

Role: STUDY_DIRECTOR

HOSPITAL UNIVERSITARIO DE BELLVITGE, BARCELONA

María Teresa Macarulla-Mercadé

Role: STUDY_DIRECTOR

HOSPITAL UNIVERSITARIO VALL D´HEBRON, UNIVERSIDAD AUTONOMA DE BARCELONA

Begoña Navalpotro-Yagüe

Role: STUDY_DIRECTOR

HOSPITAL UNIVERSITARIO VALL D´HEBRON, UNIVERSIDAD AUTONOMA DE BARCELONA

Florian Castet

Role: STUDY_CHAIR

HOSPITAL UNIVERSITARIO VALL D´HEBRON, UNIVERSIDAD AUTONOMA DE BARCELONA

Julio Santoyo

Role: STUDY_CHAIR

HOSPITAL REGIONAL UNIVERSITARIO DE MALAGA

Manuel Durán Martínez

Role: STUDY_CHAIR

HOSPITAL UNIVERSITARIO REINA SOFIA DE CÓRDOBA

Natalia Zambudio

Role: STUDY_CHAIR

Hospital Virgen de las Nieves (Granada)

Locations

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Department of HPB Surgery and Transplants, Hospital Vall d´Hebron

Barcelona, , Spain

Site Status RECRUITING

Countries

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Spain

Central Contacts

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CRISTINA DOPAZO, MD/PhD

Role: CONTACT

+34932746113

Facility Contacts

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Cristina Dopazo, PhD/MD

Role: primary

+34932746000 ext. 6113

References

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Jarnagin WR, Fong Y, DeMatteo RP, Gonen M, Burke EC, Bodniewicz BS J, Youssef BA M, Klimstra D, Blumgart LH. Staging, resectability, and outcome in 225 patients with hilar cholangiocarcinoma. Ann Surg. 2001 Oct;234(4):507-17; discussion 517-9. doi: 10.1097/00000658-200110000-00010.

Reference Type RESULT
PMID: 11573044 (View on PubMed)

Heimbach JK, Gores GJ, Haddock MG, Alberts SR, Nyberg SL, Ishitani MB, Rosen CB. Liver transplantation for unresectable perihilar cholangiocarcinoma. Semin Liver Dis. 2004 May;24(2):201-7. doi: 10.1055/s-2004-828896.

Reference Type RESULT
PMID: 15192792 (View on PubMed)

Rea DJ, Heimbach JK, Rosen CB, Haddock MG, Alberts SR, Kremers WK, Gores GJ, Nagorney DM. Liver transplantation with neoadjuvant chemoradiation is more effective than resection for hilar cholangiocarcinoma. Ann Surg. 2005 Sep;242(3):451-8; discussion 458-61. doi: 10.1097/01.sla.0000179678.13285.fa.

Reference Type RESULT
PMID: 16135931 (View on PubMed)

Darwish Murad S, Kim WR, Harnois DM, Douglas DD, Burton J, Kulik LM, Botha JF, Mezrich JD, Chapman WC, Schwartz JJ, Hong JC, Emond JC, Jeon H, Rosen CB, Gores GJ, Heimbach JK. Efficacy of neoadjuvant chemoradiation, followed by liver transplantation, for perihilar cholangiocarcinoma at 12 US centers. Gastroenterology. 2012 Jul;143(1):88-98.e3; quiz e14. doi: 10.1053/j.gastro.2012.04.008. Epub 2012 Apr 12.

Reference Type RESULT
PMID: 22504095 (View on PubMed)

Ethun CG, Lopez-Aguiar AG, Anderson DJ, Adams AB, Fields RC, Doyle MB, Chapman WC, Krasnick BA, Weber SM, Mezrich JD, Salem A, Pawlik TM, Poultsides G, Tran TB, Idrees K, Isom CA, Martin RCG, Scoggins CR, Shen P, Mogal HD, Schmidt C, Beal E, Hatzaras I, Shenoy R, Cardona K, Maithel SK. Transplantation Versus Resection for Hilar Cholangiocarcinoma: An Argument for Shifting Treatment Paradigms for Resectable Disease. Ann Surg. 2018 May;267(5):797-805. doi: 10.1097/SLA.0000000000002574.

Reference Type RESULT
PMID: 29064885 (View on PubMed)

Other Identifiers

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hCCA-LT

Identifier Type: -

Identifier Source: org_study_id

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