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Bile Duct CancerPhase 2/3AMEBICANCT02591030

Safety and Efficacy of Modified Folfirinox Versus Gemcis in Bile Duct Tumours

A Phase 2/3 study testing GEMCIS and mFolfirinox in people with Bile Duct Cancer, run by Centre Hospitalier Universitaire de Saint Etienne at 42 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Bile Duct Cancer
What is being tested?
GEMCIS and mFolfirinox
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
191 participants
Where
42 sitesFrance
Study dates
15 Dec 2015to 16 Jan 2020
Phase
Phase 2/3
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • - 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
Show all 13Show fewer
  • 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

Who cannot join

  • - 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.

Trial locations and contacts

42 sites in 1 country.

42 sites in 1 country

France42 sites

  • Chu Picardie

    Amiens

  • Ico Paul Papin

    Angers

  • CH Victor Dupouy

    Argenteuil

  • CH de la Côte Basque

    Bayonne, 64109

  • CHRU Besançon

    Besançon

  • Hôpital Avicenne

    Bobigny

  • Hôpital Saint-André

    Bordeaux, 33000

  • Polyclinique Nord

    Bordeaux, 33000

  • Hôpital Duchenne

    Boulogne-sur-Mer

  • Centre François Baclesse

    Caen

  • Chu D'Estaing

    Clermont-Ferrand

  • Hôpitaux Civils

    Colmar

  • Ch Sud Francilien

    Corbeil-Essonnes, 91100

  • Centre de radiothérapie et oncologie du Parc

    Dijon, 21000

  • Centre Georges François Leclerc

    Dijon

  • Hôpital Michallon

    Grenoble

  • CHD Vendée

    La Roche-sur-Yon

  • Clinique du cap d'Or

    La Seyne-sur-Mer

  • CH Le Kremlin Bicetre

    Le Kremlin-Bicêtre

  • CHRU Lille

    Lille

  • Centre Hospitalier de Longjumeau

    Longjumeau, 91160

  • Clinique de la Sauvegarde

    Lyon, 69000

  • Centre Léon Bérard

    Lyon

  • Hôpital de la Croix Rousse

    Lyon

  • Hôpital Lyon Sud

    Lyon

  • Hôpital Saint-Joseph

    Marseille

  • Centre Catherine de Sienne

    Nantes

  • CHR Orléans

    Orléans

  • HEGP

    Paris

  • Hôpital Cochin

    Paris

  • Hôpital Saint-Jean

    Perpignan

  • CHU La Miletrie

    Poitiers

  • CHU Reims

    Reims

  • Centre Eugène Marquis

    Rennes

  • Hôpital Drôme Nord

    Romans-sur-Isère

  • Chu Rouen

    Rouen

  • CHU Saint-Etienne

    Saint-Etienne, 42055

  • CH Saint-Jean de Luz

    Saint-Jean-de-Luz, 64500

  • CH Saint-Quentin

    Saint-Quentin

  • Ch Robert Morlevat

    Semur-en-Auxois

  • CAC Paul Strauss

    Strasbourg, 67065

  • CHU Tours

    Tours

Other trials in France

About this study

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

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%.

Read more

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.

Read the 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.

Being tested
GEMCIS, mFolfirinox
Keywords
Bile Duct Cancer, phase II/III, Modified folfirinox, Gemcis
Medical subject headings
Bile Duct Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GEMCISDrug

    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.

  • mFolfirinoxDrug

    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
Study groups in NCT02591030
Study groupRoleWhat they receive
GEMCISPlacebo comparatorNot described
Receives: Drug: GEMCIS
mFOLFIRINOXExperimentalNot described
Receives: Drug: mFolfirinox

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

    Measured: up to 6 months

  2. 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.

    Measured: up to 6 years

Secondary outcomes (8)

  1. overall survival

    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.

    Measured: up to 6 months

  2. Tumour response

    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.

    Measured: up to 6 months

  3. Tumour response

    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.

    Measured: up to 6 years

  4. Toxicity of the treatment assessed according to NCI-CTC v 4.0

    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)

    Measured: up to 6 months

  5. Toxicity of the treatment assessed according to NCI-CTC v 4.0

    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)

    Measured: up to 6 years

  6. Biliary complications

    In phase III : angiocholitis, obstruction of the main bile ducts or biliary stent obstruction

    Measured: up to 6 years

  7. Biliary complications

    In phase II : angiocholitis, obstruction of the main bile ducts or biliary stent obstruction

    Measured: up to 6 months

  8. quality of life (EORTC QLQ-C30 )

    EORTC QLQ-C30 quality of life. Quality-of-life assessments will be performed until progression of the disease

    Measured: up to 6 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Oct 2015 (estimated)
  2. Study start15 Dec 2015
  3. Primary completion27 Jun 2018
  4. Study completion16 Jan 2020

Resources

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 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
191 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02591030
Sponsor's protocol ID
1408212
Other IDs
2015-002282-35, 2015
Acronym
AMEBICA
Status last verified
Feb 2022
First submitted
26 Oct 2015
Last updated
24 Feb 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 34662180

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing GEMCIS and mFolfirinox in people with Bile Duct Cancer, run by Centre Hospitalier Universitaire de Saint Etienne at 42 sites 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 13 inclusion and 7 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: finished, as of the sponsor's last update on 24 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 42 sites 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

percentage of patients who are alive without radiological progession (time frame: up to 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02591030, which also lists 1 linked publication.

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 24 Feb 2022.

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