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Trial record 1 of 1 for:    2015-002282-35
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Safety and Efficacy of Modified Folfirinox Versus Gemcis in Bile Duct Tumours (AMEBICA)

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ClinicalTrials.gov Identifier: NCT02591030
Recruitment Status : Recruiting
First Posted : October 29, 2015
Last Update Posted : June 27, 2017
Sponsor:
Collaborator:
Federation Francophone de Cancerologie Digestive
Information provided by (Responsible Party):
Centre Hospitalier Universitaire de Saint Etienne

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.


Condition or disease Intervention/treatment Phase
Bile Duct Cancer Drug: GEMCIS Drug: mFolfirinox Phase 2 Phase 3

Detailed Description:

At the same time as these results, triple therapies involving 5FU + oxiplatin + irinotecan have objectively shown a significant increase in overall survival of patients with metastatic pancreatic adenocarcinoma compared to gemcitabine alone (median of 11.1 months versus 6.8 months, HR = 0.57 [0.45 - 0.73] p < 0.0001). The response rate and progression-free survival (PFS) have also been improved with these triple therapies; the response rates were 31.6% versus 9.4% p < 0.001 and the median PFS 6.4 months versus 3.3 months p < 0.001, respectively.

The adverse events observed with the triple therapy occurred more frequently, for febrile neutropaenia (5.4%), with the need to treat with growth factors (G-CSF for 42.5% of patients). Haematological and digestive toxicity was also higher: grade 3-4 neutropaenia was observed for 45.7% of patients in the FOLFIRINOX arm and 18.7% of patients in the gemcitabine arm (p = 0.0001); vomiting was noted for 14.5% of patients in the FOLFIRINOX arm and 4.7% in the gemcitabine arm (p = 0.002). Quality of life was improved in the FOLFIRINOX arm.

Due to the histological, therapeutic and prognostic similarities between pancreatic and bile duct cancer, it is interesting to assess this triple therapy compared to the current reference treatment in bile duct cancers: gemcitabine combined with cisplatin (GEMCIS). Due to the known higher levels of toxicity for this triple therapy (digestive and haematological), the investigators modified the conventional FOLFIRINOX regimen (mFOLFIRINOX) by removing the 5-FU bolus at D1 of each cycle. This modification to the regimen would appear not to decrease the efficacy of the treatment.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 316 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : December 15, 2015
Estimated Primary Completion Date : September 2023
Estimated Study Completion Date : September 2023

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Placebo Comparator: GEMCIS Drug: GEMCIS

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.
Experimental: mFOLFIRINOX Drug: mFolfirinox

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



Primary Outcome Measures :
  1. percentage of patients who are alive without radiological progession [ Time Frame: up to 6 months ]

    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).


  2. overall survival [ Time Frame: up to 6 years ]
    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.


Secondary Outcome Measures :
  1. overall survival [ Time Frame: up to 6 months ]
    In phase II, 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.

  2. Tumour response [ Time Frame: up to 6 months ]
    In phase II, the best tumour response will be assessed across all the treatments and will be described using the figures for the different categories: complete response, partial response, stable, progression or non-assessable.

  3. Tumour response [ Time Frame: up to 6 years ]
    In phase III, the best tumour response will be assessed across all the treatments and will be described using the figures for the different categories: complete response, partial response, stable, progression or non-assessable.

  4. Toxicity of the treatment assessed according to NCI-CTC v 4.0 [ Time Frame: up to 6 months ]
    In phase II, different types of toxicity assessed according to NCI-CTC v 4.0. Type of toxicity : Haematological (platelets and Neutrophils), Non-haematological (except for nausea, vomiting and alopecia) and neurological (paraesthesia)

  5. Toxicity of the treatment assessed according to NCI-CTC v 4.0 [ Time Frame: up to 6 years ]
    In phase III, different types of toxicity assessed according to NCI-CTC v 4.0. Type of toxicity : Haematological (platelets and Neutrophils), Non-haematological (except for nausea, vomiting and alopecia) and neurological (paraesthesia)

  6. Biliary complications [ Time Frame: up to 6 years ]
    In phase III : angiocholitis, obstruction of the main bile ducts or biliary stent obstruction

  7. Biliary complications [ Time Frame: up to 6 months ]
    In phase II : angiocholitis, obstruction of the main bile ducts or biliary stent obstruction

  8. quality of life (EORTC QLQ-C30 ) [ Time Frame: up to 6 years ]
    EORTC QLQ-C30 quality of life. Quality-of-life assessments will be performed until progression of the disease



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • - 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

Exclusion Criteria:

  • - 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.

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): NCT02591030


Contacts
Contact: Jean-Marc Phelip, PhD (0)477828320 ext +33 j.marc.phelip@chu-st-etienne.fr
Contact: Lila GABA-BERKOUK (0)3 80 39 34 83 ext +33 lila.gaba@u-bourgogne.fr

Locations
France
Chu Picardie Recruiting
Amiens, France
Principal Investigator: Vincent Heutefeuille         
Ico Paul Papin Recruiting
Angers, France
Principal Investigator: Olivier Capitain         
CH Victor Dupouy Recruiting
Argenteuil, France
Principal Investigator: Arnaud BOUTAN-LAROZE         
CH de la Côte Basque Recruiting
Bayonne, France, 64109
Principal Investigator: Franck AUDEMAR         
CHRU Besançon Recruiting
Besançon, France
Principal Investigator: Marine Jarry         
Hôpital Avicenne Not yet recruiting
Bobigny, France
Principal Investigator: Thomas Aparicio         
Hôpital Saint-André Recruiting
Bordeaux, France, 33000
Principal Investigator: Jean-Frédéric Blanc         
Polyclinique Nord Recruiting
Bordeaux, France, 33000
Principal Investigator: Cedric Lecaille         
Hôpital Duchenne Recruiting
Boulogne sur Mer, France
Principal Investigator: Vincent Bourgeois         
Centre François Baclesse Recruiting
Caen, France
Principal Investigator: Aurélie PARZY         
Chu D'Estaing Recruiting
Clermont-Ferrand, France
Principal Investigator: Caroline Petorin         
Hôpitaux Civils Recruiting
Colmar, France
Principal Investigator: Laurianne Plastaras         
Ch Sud Francilien Recruiting
Corbeil-ESSONES, France, 91100
Principal Investigator: Samy LOUAFI         
Centre de radiothérapie et oncologie du Parc Recruiting
Dijon, France, 21000
Principal Investigator: Ariane DARUT-JOUVE         
Centre Georges François Leclerc Recruiting
Dijon, France
Principal Investigator: François GHIRINGHELLI         
Hôpital Michallon Recruiting
Grenoble, France
Principal Investigator: Thomas DECAENS         
CHD Vendée Recruiting
La Roche sur Yon, France
Principal Investigator: Roger Faroux         
Clinique du cap d'Or Recruiting
La Seyne sur Mer, France
Principal Investigator: Mounira EL DEMERY         
CH Le Kremlin Bicetre Recruiting
Le Kremelin-Bicêtre, France
Principal Investigator: Anne THIROT-BIDAULT         
CHRU Lille Recruiting
Lille, France
Principal Investigator: Stéphane CATTAN         
Centre Hospitalier de Longjumeau Recruiting
Longjumeau, France, 91160
Principal Investigator: Samy LOUAFI         
Clinique de la Sauvegarde Not yet recruiting
Lyon, France, 69000
Principal Investigator: Isabelle Moullet         
Centre Léon Bérard Recruiting
Lyon, France
Principal Investigator: Françoise DESSEIGNE         
Hôpital de la Croix Rousse Recruiting
Lyon, France
Principal Investigator: Marielle Guillet         
Hôpital Lyon Sud Recruiting
Lyon, France
Principal Investigator: Marion Chauvenet         
Hôpital Saint-Joseph Recruiting
Marseille, France
Principal Investigator: Hervé Perrier         
Centre Catherine de Sienne Recruiting
Nantes, France
Principal Investigator: Hélène Castanie         
CHR Orléans Recruiting
Orléans, France
Principal Investigator: Jérome Meunier         
HEGP Recruiting
Paris, France
Principal Investigator: Julien TAIEB         
Hôpital Cochin Recruiting
Paris, France
Principal Investigator: Romain Coriat         
Hôpital Saint-Jean Recruiting
Perpignan, France
Principal Investigator: Faiza KHEMISSA-AKOUZ         
CHU La Miletrie Recruiting
Poitiers, France
Principal Investigator: David Tougeron         
CHU Reims Recruiting
Reims, France
Principal Investigator: Alexandra Heurgue         
Centre Eugène Marquis Recruiting
Rennes, France
Principal Investigator: Julien Edeline         
Hôpital Drôme Nord Recruiting
Romans sur Isère, France
Principal Investigator: Marie-Claude Goutttebel         
Chu Rouen Recruiting
Rouen, France
Principal Investigator: Pierre Michel         
CHU Saint-Etienne Recruiting
Saint-Etienne, France, 42055
Principal Investigator: Jean-Marc Phelip, PhD         
CH Saint-Jean de Luz Recruiting
Saint-Jean de Luz, France, 64500
Principal Investigator: Etienne Mauriac         
CH Saint-Quentin Recruiting
Saint-Quentin, France
Principal Investigator: Innocenti DADAMESSI         
Ch Robert Morlevat Recruiting
Semur en Auxois, France
Principal Investigator: Arnaud Patenotte         
CAC Paul Strauss Recruiting
Strasbourg, France, 67065
Principal Investigator: Meher BEN ABDELGHANI         
CHU Tours Recruiting
Tours, France
Principal Investigator: Thierry Lecomte         
Sponsors and Collaborators
Centre Hospitalier Universitaire de Saint Etienne
Federation Francophone de Cancerologie Digestive
Investigators
Principal Investigator: Jean-Marc Phelip, PhD CHU Saint-Etienne

Responsible Party: Centre Hospitalier Universitaire de Saint Etienne
ClinicalTrials.gov Identifier: NCT02591030     History of Changes
Other Study ID Numbers: 1408212
2015-002282-35 ( EudraCT Number )
First Posted: October 29, 2015    Key Record Dates
Last Update Posted: June 27, 2017
Last Verified: June 2017

Keywords provided by Centre Hospitalier Universitaire de Saint Etienne:
Bile Duct Cancer
phase II/III
Modified folfirinox
Gemcis

Additional relevant MeSH terms:
Bile Duct Neoplasms
Cholangiocarcinoma
Biliary Tract Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Bile Duct Diseases
Biliary Tract Diseases
Digestive System Diseases
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type