CholangiocarcinomaTRANSPHILNCT02232932
Liver Resection Versus Radio-chemotherapy-Transplantation for Hilar Cholangiocarcinoma
A study testing CAPECITABINE-Radiotherapy -Liver Transplantation and RESECTION in people with Cholangiocarcinoma, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
A prospective, open-label, randomised, multicentre, comparative study in two parallel groups comparing an interventional group with liver transplantation preceded by neoadjuvant radio-chemotherapy and a control group receiving conventional liver and bile duct resection. Read more about this study
- Who is it for?
- Ages 18 to 68 years
- Conditions the study is for
- Cholangiocarcinoma
- What is being tested?
- CAPECITABINE-Radiotherapy -Liver Transplantation and RESECTION
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteFrance
- Study dates
- Mar 2014to Sep 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 68 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients (male or female) aged from 18 to 68 year-old, French
- Hilar cholangiocarcinoma histologically proved and/or highly suspected on hilar stenosis with mass syndrome from 0.1 cm to 3 cm
- Hilar cholangiocarcinoma type 2, type 3A, type 3B, type 4
- Patients considered as resectable (R0 resection) by liver resection including segment 1 and biliary confluence with or without vascular resection
- Patient potentially transplantable
- Patient affiliated to French Health Insurance
- Patient who had sign an informed consent
Who cannot join
- Pregnant or breastfeeding woman
- Women of childbearing potential without an effective contraception method
- Radiotherapy contraindication
- Positive dosage of ImmunoglobulinsG4 (IgG4)
- dihydro-pyrimidine-dehydrogenase (DPD) total deficit
- Personal history of cancer in the last 5 five years (exclusion basocellular cellular carcinoma)
Show all 23Show fewer
- Personal history of fluoropyrimidine hypersensibility
- Personal history of capecitabine hypersensibility
- Personal history of dihydro-pyrimidine-dehydrogenase deficit
- Polynuclear neutrophil < 1500 / ml
- Platelet rate < 100 000 / ml
- Severe leucopenia < 2000 / ml
- Severe liver failure (Factor V < 50%)
- Severe renal failure (Creatin clearance < 30 ml/min)
- Treatment by Sorivudine or its analogue as Brivudine
- Non controled diabetes mellitus and/or others severe co-morbidities (renal failure, severe and instable coronaropathy, severe risk factor of stroke, body mass index superior to 35)
- Proved histological cirrhosis
- Sclerosing cholangitis
- Intra and/or extra-hepatic metastases
- Hypereosinophilia and/or wirsung dilatation and/or mass of the pancreas head
- Hilar mass superior to 3 cm
- Duodenal invasion
- Patient under guardianship
Trial locations and contacts
1 site in 1 country.
France1 site
AP-HP, Paul Brousse Hospital, Centre Hepato-Biliaire
Villejuif, 94
About this study
Official title: Randomized Prospective Multicentric Study: Radio-chemotherapy and Liver Transplantation Versus Liver Resection to Treat Respectable Hilar Cholangiocarcinoma
A prospective, open-label, randomised, multicentre, comparative study in two parallel groups comparing an interventional group with liver transplantation preceded by neoadjuvant radio-chemotherapy and a control group receiving conventional liver and bile duct resection.
The primary endpoint will be overall survival at 5 years in the intent-to-treat population. The secondary endpoint will be recurrence-free survival at 3 years evaluated by CT-scan and tumoral markers (Carcinoembryonic antigen (CAE) and cancer antigen (CA19.9)) in the intent-to-treat population.
The number of subjects necessary is 54 patients (27 x 2): this population will enable the demonstration of a significant difference is 5-year survival rates between the transplanted group and the resected group with a power of 80% and a first-species risk of 5%, under the hypothesis that these survival rates are 70% in the transplanted group and 30% in the resected group.
Read the detailed description
The protocol will comprise a phase 1 during which the potential eligibility of patients (presenting with a resectable Klatskin - Excepted Type 1of Bismuth) will be assessed, based on clinical, biological and morphological data. After phases 1, the eligibility of the patient will be confirmed or not. In the context of the study, phase 2 will include the collection of blood samples as well as positon emission tomography (PET)-scan and upper endoscopic ultrasound (EUS) in order to rule out any obvious lymph node metastases. A short exploratory laparoscopy will also be performed in phase 2 to eliminate infra-clinic subcapsular liver metastases and peritoneal carcinomatosis. The randomization process will take place at the end of the phase 2, patients will be assigned into the transplantation arm (OLT) or the resection arm (RSX). During phase 3, patient will receive nutritional support and, if not done previously, a biliary drainage will be placed endoscopically. In the RSX arm (phase 3A), patients will undergo radical resection of the tumor (refer below technical details). Preoperative portal vein embolization may be necessary at this stage depending on the expected remnant liver volume, assessed by CT-scan volumetry. In the OLT arm (phase 3A), patients will receive neoadjuvant radiochemotherapy (External - 50 grays) following by liver transplantation (phase 4B). Before the fifth week after completion of radiochemotherapy, a staging laparotomy with local lymphadenectomy will be performed and patients will be put on the national waiting list in the absence of extra-hepatic disease, especially peritoneal seeding and lymph nodes involvement. A score exception will allowed a liver transplantation in the 3 months after staging laparotomy. During phase 5 the patient will be monitored postoperatively at the clinical, biological and morphological levels for 3 months. During phase 6, the patient will be followed clinically, biologically and morphologically for 5 years in order to detect any recurrence and in the context of standard clinical care.
- Conditions
- Cholangiocarcinoma
- Being tested
- CAPECITABINE-Radiotherapy -Liver Transplantation, RESECTION
- Keywords
- Hilar cholangiocarcinoma, Liver transplantation, Radiochemotherapy
- Medical subject headings
- Cholangiocarcinoma, Klatskin Tumor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CAPECITABINE-Radiotherapy -Liver TransplantationProcedure or surgery
Also called Neoadjuvant Radio-Chemotherapy and Liver Transplantation
CAPECITABINE (800 mg/m2 twice a day during 5 weeks) + External Radiotherapy (50 grays during 5 weeks) then Liver transplantation
RESECTIONProcedure or surgery
Also called Liver Resection
Intent-to-treat R0 liver resection
| Study group | Role | What they receive |
|---|---|---|
| CAPECITABINE-Radiotherapy -Liver Transplantation | Experimental | Neoadjuvant Radio-Chemotherapy (RC) and Liver Transplantation (LT) Receives: Procedure: CAPECITABINE-Radiotherapy -Liver Transplantation |
| RESECTION | Active comparator | Liver resection Receives: Procedure: RESECTION |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival
To demonstrate the superiority, in terms of 5-year survival, of liver transplantation (TH) preceded by neoadjuvant chemoradiotherapy on the radical resection of Klatskin tumors considered resectable
Measured: At 5 years
Secondary outcomes (1)
Recurrence free survival
3-year recurrence-free survival assessed by CT and markers
Measured: At 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2014 (estimated)
- Study startMar 2014
- Primary completionFeb 2024 (estimated)
- Study completionSep 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CholangiocarcinomaStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Eric VIBERT, MD, Principal investigator, AP-HP, Paul Brousse Hospital, Centre Hepato-Biliaire, Villejuif, France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02232932
- Sponsor's protocol ID
- P120106
- Acronym
- TRANSPHIL
- Status last verified
- Oct 2021
- First submitted
- 6 Aug 2014
- Last updated
- 3 Nov 2021
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Prospective Multicentric Study: Radio-chemotherapy and Liver Transplantation Versus Liver Resection to Treat Respectable Hilar Cholangiocarcinoma
- ClinicalTrials.gov ID
- NCT02232932
- Acronym / sponsor ID
- TRANSPHIL / P120106
- Conditions
- Cholangiocarcinoma
- Keywords
- Hilar cholangiocarcinoma, Liver transplantation, Radiochemotherapy
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Mar 2014
- Primary completion
- Feb 2024 (estimated)
- Study completion
- Sep 2024 (estimated)
- First posted
- 5 Sep 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A prospective, open-label, randomised, multicentre, comparative study in two parallel groups comparing an interventional group with liver transplantation preceded by neoadjuvant radio-chemotherapy and a control group receiving conventional liver and bile duct resection.
The primary endpoint will be overall survival at 5 years in the intent-to-treat population. The secondary endpoint will be recurrence-free survival at 3 years evaluated by CT-scan and tumoral markers (Carcinoembryonic antigen (CAE) and cancer antigen (CA19.9)) in the intent-to-treat population.
The number of subjects necessary is 54 patients (27 x 2): this population will enable the demonstration of a significant difference is 5-year survival rates between the transplanted group and the resected group with a power of 80% and a first-species risk of 5%, under the hypothesis that these survival rates are 70% in the transplanted group and 30% in the resected group.
Detailed description
The protocol will comprise a phase 1 during which the potential eligibility of patients (presenting with a resectable Klatskin - Excepted Type 1of Bismuth) will be assessed, based on clinical, biological and morphological data. After phases 1, the eligibility of the patient will be confirmed or not. In the context of the study, phase 2 will include the collection of blood samples as well as positon emission tomography (PET)-scan and upper endoscopic ultrasound (EUS) in order to rule out any obvious lymph node metastases. A short exploratory laparoscopy will also be performed in phase 2 to eliminate infra-clinic subcapsular liver metastases and peritoneal carcinomatosis. The randomization process will take place at the end of the phase 2, patients will be assigned into the transplantation arm (OLT) or the resection arm (RSX). During phase 3, patient will receive nutritional support and, if not done previously, a biliary drainage will be placed endoscopically. In the RSX arm (phase 3A), patients will undergo radical resection of the tumor (refer below technical details). Preoperative portal vein embolization may be necessary at this stage depending on the expected remnant liver volume, assessed by CT-scan volumetry. In the OLT arm (phase 3A), patients will receive neoadjuvant radiochemotherapy (External - 50 grays) following by liver transplantation (phase 4B). Before the fifth week after completion of radiochemotherapy, a staging laparotomy with local lymphadenectomy will be performed and patients will be put on the national waiting list in the absence of extra-hepatic disease, especially peritoneal seeding and lymph nodes involvement. A score exception will allowed a liver transplantation in the 3 months after staging laparotomy. During phase 5 the patient will be monitored postoperatively at the clinical, biological and morphological levels for 3 months. During phase 6, the patient will be followed clinically, biologically and morphologically for 5 years in order to detect any recurrence and in the context of standard clinical care.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CAPECITABINE-Radiotherapy -Liver Transplantation | Experimental | Procedure: CAPECITABINE-Radiotherapy -Liver TransplantationNeoadjuvant Radio-Chemotherapy (RC) and Liver Transplantation (LT) |
| RESECTION | Active comparator | Procedure: RESECTIONLiver resection |
Who may qualify
- Ages
- 18 to 68 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patients (male or female) aged from 18 to 68 year-old, French
- Hilar cholangiocarcinoma histologically proved and/or highly suspected on hilar stenosis with mass syndrome from 0.1 cm to 3 cm
- Hilar cholangiocarcinoma type 2, type 3A, type 3B, type 4
- Patients considered as resectable (R0 resection) by liver resection including segment 1 and biliary confluence with or without vascular resection
- Patient potentially transplantable
Key exclusion criteria (23 listed)
- Pregnant or breastfeeding woman
- Women of childbearing potential without an effective contraception method
- Radiotherapy contraindication
- Positive dosage of ImmunoglobulinsG4 (IgG4)
- dihydro-pyrimidine-dehydrogenase (DPD) total deficit
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CAPECITABINE-Radiotherapy -Liver TransplantationAlso: Neoadjuvant Radio-Chemotherapy and Liver TransplantationCAPECITABINE (800 mg/m2 twice a day during 5 weeks) + External Radiotherapy (50 grays during 5 weeks) then Liver transplantation | Procedure or surgery | CAPECITABINE-Radiotherapy -Liver Transplantation |
| RESECTIONAlso: Liver ResectionIntent-to-treat R0 liver resection | Procedure or surgery | RESECTION |
Primary outcome
Overall survival
Time frame: At 5 years
To demonstrate the superiority, in terms of 5-year survival, of liver transplantation (TH) preceded by neoadjuvant chemoradiotherapy on the radical resection of Klatskin tumors considered resectable
1 secondary outcome
Recurrence free survival
Time frame: At 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2021.
Related trials for Cholangiocarcinoma
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
Active, not recruitingPhase 2/3
A Study of CTX-009 in Combination With Paclitaxel in Adult Patients With Unresectable Advanced, Metastatic or Recurrent Biliary Tract Cancers (COMPANION-002)
Biliary Tract Cancer, Cholangiocarcinoma
Active, not recruitingPhase 1
Prospective Exploratory Study of FAPi PET/CT With Histopathology Validation in Patients With Various Cancers
Bladder Carcinoma, Cervical Carcinoma
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma
Active, not recruitingObservational study
Liver Cancer Registry Platform
Hepatocellular Carcinoma (HCC), Cholangiocarcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eric VIBERT, MD principal investigator
AP-HP, Paul Brousse Hospital, Centre Hepato-Biliaire, Villejuif, France
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing CAPECITABINE-Radiotherapy -Liver Transplantation and RESECTION in people with Cholangiocarcinoma, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 3 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall survival (time frame: At 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Nov 2021.