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

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ClinicalTrials.gov Identifier: NCT04378023
Recruitment Status : Recruiting
First Posted : May 7, 2020
Last Update Posted : June 1, 2020
Sponsor:
Information provided by (Responsible Party):
Cristina Dopazo Taboada, Hospital Vall d'Hebron

Brief Summary:

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. 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.


Condition or disease Intervention/treatment Phase
Unresectable Cholangiocarcinoma Drug: Neoadjuvant Chemo-radiotherapy Procedure: Liver Transplantation Phase 4

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.

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 34 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Liver Transplant Combined With Neoadjuvant Chemo-radiotherapy in the Treatment of Unresectable Hilar Cholangiocarcinoma. A Prospective Multicenter Study.
Actual Study Start Date : April 24, 2020
Estimated Primary Completion Date : June 1, 2025
Estimated Study Completion Date : June 1, 2025


Arm 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.




Primary Outcome Measures :
  1. Overall survival at 1, 3, and 5 years post-transplant [ Time Frame: 5 years ]

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


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04378023


Contacts
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Contact: CRISTINA DOPAZO, MD/PhD +34932746113 cdopazo@vhebron.net

Locations
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Spain
Department of HPB Surgery and Transplants, Hospital Vall d´Hebron Recruiting
Barcelona, Spain, 08035
Contact: Cristina Dopazo, PhD/MD    +34932746000 ext 6113    cdopazo@vhebron.net   
Sponsors and Collaborators
Hospital Vall d'Hebron
Investigators
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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 ROCIO, 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 MARQUES DE VALDECILLA, SANTANDER
Study Chair: Josefina López-Domínguez HOSPITAL UNIVERSITARIO DE BELLVITGE, BARCELONA
Study Chair: Helena Verdaguer-Mata HOSPITAL UNIVERSITARIO VALL D´HEBRON, UNIVERSIDAD AUTONOMA, 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: Agustín García-Gil 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: Constantino Fondevila-Campo Hospital Clinic of 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
Publications of Results:

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Responsible Party: Cristina Dopazo Taboada, Consultant Surgeon, Hospital Vall d'Hebron
ClinicalTrials.gov Identifier: NCT04378023    
Other Study ID Numbers: hCCA-LT
First Posted: May 7, 2020    Key Record Dates
Last Update Posted: June 1, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Additional relevant MeSH terms:
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Cholangiocarcinoma
Klatskin Tumor
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms