Safety and Efficacy of Modified Folfirinox Versus Gemcis in Bile Duct Tumours
AMEBICA
Randomised Phase II/III Study, Assessing the Safety and Efficacy of Modified Folfirinox Versus Gemcis in Locally Advanced, Unresectable and/or Metastatic Bile Duct Tumours
2 other identifiers
interventional
191
1 country
42
Brief Summary
Bile duct tumours are rare. They are the 6th most common type of digestive cancer. Their therapeutic management is complex and must be multidisciplinary in nature. Most of the time, an endoscopic or radiological biliary drainage is necessary before any tumour treatment. Their prognosis is poor due to the fact that they are normally diagnosed late, which makes curative surgery impossible. A population study in the Côte d'Or region of France reported a survival rate at 5 years of approximately 10%. For the locally advanced or metastatic forms, treatment has not been properly codified. With respect to chemotherapy, prospective studies, most often phase II, are difficult to interpret due to a limited number of patients and due to the heterogeneity of this type of tumour (bile duct and pancreas tumours). Treatment with 5FU alone provides an objective response in approximately 10% of cases. In combination with mitomycin or carboplatin, the objective response rate is 20%, with a median survival period of 5 months. Interferon combined with 5FU has a better response rate (30%), but occurrences of different types of toxicity are more frequent. More recently, gemcitabine and the 5FU-cisplatin combinations demonstrated objective tumour control in 50% of patients with a median survival period of 10 months. Gemcitabine combined with oxiplatin or with cisplatin has shown the same response rate but a median survival period of approximately 12 months. The benefit of this combination has been confirmed in a phase III trial that compared the gemcitabine-cisplatin combination to gemcitabine alone, in 410 patients with locally advanced unresectable and/or metastatic bile duct cancer. The results were in favour of the combined treatment with a median survival period of 11.7 months (versus 8.1 months - HR 0.64 \[0.52 - 0.80\]). This combination is currently the reference first-line treatment.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Dec 2015
Typical duration for phase_2
42 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 26, 2015
CompletedFirst Posted
Study publicly available on registry
October 29, 2015
CompletedStudy Start
First participant enrolled
December 15, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 27, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
January 16, 2020
CompletedFebruary 24, 2022
February 1, 2022
2.5 years
October 26, 2015
February 23, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
percentage of patients who are alive without radiological progession
In phase II, the primary endpoint is the percentage of patients alive without radiological progression (assessed according to the RECIST v1.1 criteria) at 6 months (after randomisation). Patients who are in radiological progression or who have died before the 6 months have elapsed will be considered a failure for the primary endpoint at 6 months (after randomisation). A medical review will be conducted to decide on patients without radiological progression at 6 months; in the light of their entire medical file, they may be considered a failure (i.e. in progression) or they may be considered to be truly non-assessable (a 5% surplus of patients has been planned for this situation).
up to 6 months
overall survival
In phase III, the primary endpoint is overall survival. This is defined as the period between the date of randomisation and the date of death (regardless of the cause). Patients who are lost to follow-up will be censored at the end-point for the analysis, or at the date when they were last heard of.
up to 6 years
Secondary Outcomes (8)
overall survival
up to 6 months
Tumour response
up to 6 months
Tumour response
up to 6 years
Toxicity of the treatment assessed according to NCI-CTC v 4.0
up to 6 months
Toxicity of the treatment assessed according to NCI-CTC v 4.0
up to 6 years
- +3 more secondary outcomes
Study Arms (2)
GEMCIS
PLACEBO COMPARATORmFOLFIRINOX
EXPERIMENTALInterventions
At D1 and D8 of each cycle, i.e. every 21 days for 6 months: * Cisplatin 25 mg/m² over 1 hour at D1 and D8 * Gemcitabine 1000 mg/m² over 30 minutes at D1 and D8.
At D1 of each cycle, i.e. every 15 days for 6 months: * Oxiplatin: 85 mg/m² (IP/120 minutes) * Irinotecan: 180 mg/m² (IV/90 minutes) * Folinic acid: 400 mg/m² (or 200 mg/m² if Elvorine \[calcium levofolinate\]) (IV/2 hours), via a Y connector at the same time as irinotecan * 5-FU: 2400 mg/m² (IV over 46 hours) without 5FU bolus at D1
Eligibility Criteria
You may qualify if:
- \- WHO 0 or 1
- Age ≥ 18 years
- Tumour of the intrahepatic or extrahepatic (and/or hilar) bile ducts, or of the gallbladder
- Measurable abdominal metastases (at least a lesion \>10 mm) and/or measurable, unresectable primary tumour
- Disease proven by histopathology or cytology (on metastasis or primary tumour)
- If there are no abdominal metastases, the unresectability must be confirmed by a hepatobiliary surgeon in a multidisciplinary team (MDT) meeting
- Bilirubin \<1.5 N (after endoscopic or trance hepatic optimum biliary drainage, if necessary), AST and ALT \<10N
- Serum creatinine \<130 µmol/L, creatinine clearance \>60 mL/min
- Neutrophils ≥ 1500/mm3 and platelets ≥ 75,000/mm3
- Prothrombin index \> 70%
- Serum albumin \> 25 g/L
- Patient registered with a social security scheme (including CMU)
- Signed informed consent form
You may not qualify if:
- \- Non-measurable metastases and primary tumour
- Ampullary carcinoma or cancer of the pancreas with infiltration of the bile ducts or mixed tumours (hepatocholangiocarcinoma)
- Chemotherapy and/or radiotherapy within the last 4 months
- Other malignant tumour except in situ basal cell carcinoma or curatively treated carcinoma of the uterine cervix or other malignant tumour that has been treated and has been considered cured for at least 5 years
- Major comorbidity factors (unstable angina, myocardial infarction that has occurred within the last 6 months, heart failure ≥2 according to the NYHA classification, uncontrolled high blood pressure)
- Woman who is pregnant or breastfeeding, or patient of either sex who is of childbearing age and not using an adequate contraceptive method
- Not able to undergo the trial medical follow-up for geographical, social or psychological reasons.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (42)
Chu Picardie
Amiens, France
Ico Paul Papin
Angers, France
CH Victor Dupouy
Argenteuil, France
CH de la Côte Basque
Bayonne, 64109, France
CHRU Besançon
Besançon, France
Hôpital Avicenne
Bobigny, France
Hôpital Saint-André
Bordeaux, 33000, France
Polyclinique Nord
Bordeaux, 33000, France
Hôpital Duchenne
Boulogne-sur-Mer, France
Centre François Baclesse
Caen, France
Chu D'Estaing
Clermont-Ferrand, France
Hôpitaux Civils
Colmar, France
Ch Sud Francilien
Corbeil-Essonnes, 91100, France
Centre de radiothérapie et oncologie du Parc
Dijon, 21000, France
Centre Georges François Leclerc
Dijon, France
Hôpital Michallon
Grenoble, France
CHD Vendée
La Roche-sur-Yon, France
Clinique du cap d'Or
La Seyne-sur-Mer, France
CH Le Kremlin Bicetre
Le Kremlin-Bicêtre, France
CHRU Lille
Lille, France
Centre Hospitalier de Longjumeau
Longjumeau, 91160, France
Clinique de la Sauvegarde
Lyon, 69000, France
Centre Léon Bérard
Lyon, France
Hôpital de la Croix Rousse
Lyon, France
Hôpital Lyon Sud
Lyon, France
Hôpital Saint-Joseph
Marseille, France
Centre Catherine de Sienne
Nantes, France
CHR Orléans
Orléans, France
HEGP
Paris, France
Hôpital Cochin
Paris, France
Hôpital Saint-Jean
Perpignan, France
CHU La Miletrie
Poitiers, France
CHU Reims
Reims, France
Centre Eugène Marquis
Rennes, France
Hôpital Drôme Nord
Romans-sur-Isère, France
Chu Rouen
Rouen, France
CHU Saint-Etienne
Saint-Etienne, 42055, France
CH Saint-Jean de Luz
Saint-Jean-de-Luz, 64500, France
CH Saint-Quentin
Saint-Quentin, France
Ch Robert Morlevat
Semur-en-Auxois, France
CAC Paul Strauss
Strasbourg, 67065, France
CHU Tours
Tours, France
Related Publications (1)
Phelip JM, Desrame J, Edeline J, Barbier E, Terrebonne E, Michel P, Perrier H, Dahan L, Bourgeois V, Akouz FK, Soularue E, Ly VL, Molin Y, Lecomte T, Ghiringhelli F, Coriat R, Louafi S, Neuzillet C, Manfredi S, Malka D; PRODIGE 38 AMEBICA Investigators/Collaborators. Modified FOLFIRINOX Versus CISGEM Chemotherapy for Patients With Advanced Biliary Tract Cancer (PRODIGE 38 AMEBICA): A Randomized Phase II Study. J Clin Oncol. 2022 Jan 20;40(3):262-271. doi: 10.1200/JCO.21.00679. Epub 2021 Oct 18.
PMID: 34662180DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Jean-Marc Phelip, PhD
CHU SAINT-ETIENNE
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 26, 2015
First Posted
October 29, 2015
Study Start
December 15, 2015
Primary Completion
June 27, 2018
Study Completion
January 16, 2020
Last Updated
February 24, 2022
Record last verified: 2022-02
Data Sharing
- IPD Sharing
- Will not share