PRODIGE 98- AMPIRINOX : Randomized, multicenter, Phase III trial of adjuvant chemotherapy with modified FOLFIRINOX versus capecitabine or gemcitabine in patients with resected ampullary adenocarcinoma.

Start 24 Sep 2024 · Status Ongoing, recruiting · 1 EU/EEA countries · 58 sites · Protocol AMPIRINOX

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)

Status Ongoing, recruiting

Participants planned 294

Countries 1

Sites 58

Ampullary adenocarcinoma

To assess efficacy of adjuvant mFOLFIRINOX versus single-agent chemotherapy (gemcitabine or capecitabine) in improving 2-year disease-free survival (DFS) after surgical resection of an ampullary adenocarcinoma

Key facts

Sponsor: Centre Hospitalier Universitaire De Dijon
Participant type: Patients
Age range: 18-64 years, 65+ years
Gender: Male and Female
Therapeutic area: Diseases [C] - Digestive System Diseases [C06], Diseases [C] - Neoplasms [C04]
Trial duration: 24 Sep 2024 → ongoing
Decision date (initial): 2024-09-24
Transition trial: No
Low-intervention: No
Rare-disease indication: No
Vulnerable population: No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

Secondary objectives 5

Overall survival (OS)
Rate of patients completing 3 and 6 monhs chemotherapy schedule according to percentage of administered dose of each product
Assessment of quality of life by EORTC QLQ-C30 and PAN26
Assessment of toxicities
Analyses on OS and DFS by prespecified subgroups

Conditions and MedDRA coding

Ampullary adenocarcinoma

Regulatory references

Plan to share IPD: No

EU CT number	Title	Sponsor
2024-511070-68-00	PRODIGE 98- AMPIRINOX : Randomized, multicenter, Phase III trial of adjuvant chemotherapy with modified FOLFIRINOX versus capecitabine or gemcitabine in patients with resected ampullary adenocarcinoma.	Centre Hospitalier Universitaire De Dijon

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

Histologically proven adenocarcinoma on surgical specimen
Macroscopically complete surgical resection of an ampullary adenocarcinoma (R0 or R1)
Adenocarcinoma removed within 12 weeks prior to enrollment
Patient without metastatic disease on CT scan < 4 weeks prior to inclusion
CA19.9 level < 180 U/L at inclusion (post-operative level)
Patients ≥ 18 years of age

Exclusion criteria 12

Neoadjuvant systemic chemotherapy
pT1N0M0 tumors
Active infection by HBV, HCV or HIV
Known dihydropyrimidine dehydrogenase deficiency (uracilemia ≥ 16 ng/mL)
Pre-existing peripheral neuropathy (grade ≥ 2)
Unresolved or uncontrolled concomitant medical conditions
Neutrophils < 1500/mm3, platelets < 150 000/mm3, Haemoglobin < 9 g/dL
Total bilirubin > 1.5x normal
Creatinine clearance < 50 ml/min according to MDRD
AST or ALT > 2.5 x UNL, alkaline phosphatase > 2.5x normal at least 15 days after resection
Patients with poor nutritional status represented by albuminemia < 30.0g/dl
History of myocardial infarction within the last 6 months, severe coronary artery disease or severe heart failure

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

The primary endpoint is the 2 years Disease-free survival rate. DFS will be calculated from date of randomization to the date of first relapse (locally and/or metastatic) or date of death (all causes). Patients alive without relapse will be censored at the date of last news. Second cancer will not be considered as an event. The relapse will be assessed by the investigator according to RECIST v1.1 criteria.

Secondary endpoints 4

OS is defined as the time between randomization and death (all causes). Patients alive will be censored at the date of last news.
Rate of patients completing 3 and 6-month chemotherapy schedule according to percentage of administered dose of each product. Percentage of administrated dose will be calculated as the ratio of dose received over dose planned for each product. A completed cycle will be defined by at least 80% of each product dispensed
All grade and grade 3-4, will be described using NCI-CTCAE (National Cancer Institute – Common Terminology Criteria for Adverse Events) version 5.0
Quality of life will be assessed according to the questionnaire of EORTC QLQ-C30 and PAN26 questionnaires.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Calcium Folinate

SUB06052MIG · Substance

Active substance: Calcium Folinate
Pharmaceutical form: SOLUTION FOR INFUSION
Route of administration: INTRAVENOUS
Max daily dose: 400 mg/m2 milligram(s)/sq. meter
Max total dose: 400 mg/m2 milligram(s)/sq. meter
Max treatment duration: 24 Week(s)
Authorisation status: Authorised
ATC code: - — -
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Oxaliplatin

SUB09490MIG · Substance

Active substance: Oxaliplatin
Pharmaceutical form: SOLUTION FOR INFUSION
Route of administration: INTRAVENOUS
Max daily dose: 85 mg/m2 milligram(s)/sq. meter
Max total dose: 85 mg/m2 milligram(s)/sq. meter
Max treatment duration: 24 Week(s)
Authorisation status: Authorised
ATC code: - — -
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Irinotecan

SUB08295MIG · Substance

Active substance: Irinotecan
Pharmaceutical form: SOLUTION FOR INFUSION
Route of administration: INTRAVENOUS
Max daily dose: 150 mg/m2 milligram(s)/sq. meter
Max total dose: 150 mg/m2 milligram(s)/sq. meter
Max treatment duration: 24 Week(s)
Authorisation status: Authorised
ATC code: - — -
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Fluorouracil

SUB07721MIG · Substance

Active substance: Fluorouracil
Pharmaceutical form: SOLUTION FOR INFUSION
Route of administration: INTRAVENOUS
Max daily dose: 2400 mg/m2 milligram(s)/sq. meter
Max total dose: 2400 mg/m2 milligram(s)/sq. meter
Max treatment duration: 24 Week(s)
Authorisation status: Authorised
ATC code: - — -
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Comparator 4

Gemcitabine Hydrochloride

SUB02324MIG · Substance

Active substance: Gemcitabine Hydrochloride
Pharmaceutical form: SOLUTION FOR INFUSION
Route of administration: INTRAVENOUS
Max daily dose: 1000 mg/m2 milligram(s)/sq. meter
Max total dose: 1000 mg/m2 milligram(s)/sq. meter
Max treatment duration: 24 Week(s)
Authorisation status: Authorised
ATC code: - — -
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Capecitabine Accord 300 mg film-coated tablets

PRD1614131 · Product

Active substance: Capecitabine
Pharmaceutical form: FILM-COATED TABLET
Route of administration: ORAL
Max daily dose: 1250 mg/m2 milligram(s)/square meter
Max total dose: 1250 mg/m2 milligram(s)/square meter
Max treatment duration: 24 Week(s)
Authorisation status: Authorised
ATC code: L01BC06 — CAPECITABINE
Marketing authorisation: EU/1/12/762/022
MA holder: ACCORD HEALTHCARE S.L.U.
MA country: EU
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Capecitabine Accord 150 mg film-coated tablets

PRD1614129 · Product

Active substance: Capecitabine
Pharmaceutical form: FILM-COATED TABLET
Route of administration: ORAL
Max daily dose: 1250 mg/m2 milligram(s)/sq. meter
Max total dose: 1250 mg/m2 milligram(s)/sq. meter
Max treatment duration: 24 Week(s)
Authorisation status: Authorised
ATC code: L01BC06 — CAPECITABINE
Marketing authorisation: EU/1/12/762/020
MA holder: ACCORD HEALTHCARE S.L.U.
MA country: EU
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Capecitabine Accord 500 mg film-coated tablets

PRD1614134 · Product

Active substance: Capecitabine
Pharmaceutical form: FILM-COATED TABLET
Route of administration: ORAL
Max daily dose: 1250 mg/m2 milligram(s)/sq. meter
Max total dose: 1250 mg/m2 milligram(s)/sq. meter
Max treatment duration: 24 Week(s)
Authorisation status: Authorised
ATC code: L01BC06 — CAPECITABINE
Marketing authorisation: EU/1/12/762/025
MA holder: ACCORD HEALTHCARE S.L.U.
MA country: EU
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Dijon

Sponsor organisation: Centre Hospitalier Universitaire De Dijon
Address: 1 Boulevard Jeanne D Arc, Bp 77908 Bp 77908
City: Dijon
Postcode: 21000
Country: France

Scientific contact point

Organisation: Centre Hospitalier Universitaire De Dijon
Contact name: Coordinator

Public contact point

Organisation: Centre Hospitalier Universitaire De Dijon
Contact name: Coordinator

Third parties 1

Organisation	City, country	Duties
Fondation Franc.Cancerologie Digestive ORG-100007358	Dijon Cedex, France	On site monitoring, Code 10, Code 14, Code 5, Data management, Code 8, Code 9

Locations

1 EU/EEA country · 58 investigational sites

By country

Country	MS status	Planned subjects	Sites
France	Ongoing, recruiting	294	58
Rest of world	—	0	—

Investigational sites

France

58 sites · Ongoing, recruiting

Les Hopitaux De Chartres

Oncology, 4 Rue Claude Bernard, 28630, Le Coudray

Groupe Hospitalier Rance Emeraude

Gastroenterology, 1 Rue De La Marne, 35403, Saint-Malo Cedex

Groupe Hospitalier Diaconesses Croix Saint Simon

Gastroenterology, 125 Rue D Avron, 75020, Paris

Centre Hospitalier Universitaire Grenoble Alpes

Digestive Oncology, Boulevard De La Chantourne, Cs 10217, Grenoble Cedex 9

Hopital Prive D Antony

Gastroenterology, 1 Rue Velpeau, 92160, Antony

Clinique Sainte Clotilde

Oncology, 127 Rte de Bois de Nefles, 97400, Saint-Denis , La Réunion

Hôpital La Timone - APHM

Oncology, 264 Rue Saint-Pierre, 13005, Marseille

Beauvais General Hospital

Onco-radiotherapy, 40 Léon Blum Avenue, 60000, Beauvais

Centre Hospitalier General De St Denis

Oncology, 2 Rue Du Docteur Delafontaine, Bp 279, St Denis Cedex

Hospices Civils De Lyon

Hepatogastroenterology, 165 Chemin Du Grand Revoyet, 69310, Pierre Benite

Centre Hospitalier Universitaire De Toulouse

Gastroenterology, 1 Avenue Du Professeur Jean Poulhes, Tsa 50032, Toulouse Cedex 9

Hôpital Foch

Medical Oncology, 40 Rue Worth, 92151, Suresnes

Centre Hospitalier De Colmar

Gastroenterology, 39 Avenue De La Liberte, Bp 60535, Colmar Cedex

Centre Hospitalier Universitaire De Poitiers

Gastroenterology, 2 Rue De La Miletrie, 86000, Poitiers

Centre Hospitalier Des Pays De Morlaix

Oncology and Hematology, 15 Rue De Kersaint Gilly, Bp 97237, Morlaix

Hopital Nord-Oest - Villefranche sur Saône

Gastroenterology, Plateau d'Ouilly - Gleizé, 69655, Villefranche sur Saône

Union Mut Gestion Groupe Hosp Mutualiste De Grenoble

Gastroenterology, 8 Rue Docteur Calmette, 38000, Grenoble

Clinique De L'Europe

Oncology, 5 Allee Des Pays Bas, 80090, Amiens

Centre Hospitalier Sud Francilien

Digestive oncology, 40 Avenue Serge Dassault, 91106, Corbeil Essonnes Cedex

CHRU De Nancy

Gastroenterology, 11 Rue Du Morvan, Bp 80001, Vandoeuvre Les Nancy Cedex

Centre Hospitalier Universitaire De Dijon

Hepatogastroenterology, 1 Boulevard Jeanne D Arc, Bp 77908, Dijon

Centre Hospitalier De Pau

Gastroenterology, 4 Boulevard Hauterive, Cs 17595, Pau Cedex

Centre Léonard de Vinci - Pôle Médical du Pont Saint Vaast

Oncology, Route de Cambrai, 59187, Dechy

Assistance Publique Hopitaux De Paris

Gastroenterology, 20 Rue Leblanc, 75015, Paris

Assistance Publique Hopitaux De Paris

Gastroenterology, 27 Rue Du Faubourg Saint Jacques, 75014, Paris

Centre Hospitalier Bethune Beuvry

Gastroenterology, 27 Rue Delbecque, 62660, Beuvry

Hopital Europeen Marseille

Digestive oncology, 6 Rue Desiree Clary, 13003, Marseille

Centre Hospitalier Universitaire Reims

Oncology, Rue Du General Koenig, 51092, Reims Cedex

Centre Hospitalier De La Cote Basque

Gastroenterology, 13 Avenue Interne Jacques Loeb, 64100, Bayonne

CHU d'Estaing

Digestive oncology, 1 place Lucie et Raymond Aubrax, 63100, Clermont-Ferrand

Institut De Cancerologie Strasbourg Europe

Gastroenterology, 17 Rue Albert Calmette, 67200, Strasbourg

Hopital Beaujon

Gastroenterology, 100 Boulevard Du General Leclerc, 92110, Clichy

Polyclinique Saint-Come

Oncology, 7 Rue Jean Jacques Bernard, 60200, Compiegne

Clinique Pasteur Lanroze

Oncology, 32 Rue Auguste Kervern, 29200, Brest

Centre Hospitalier Prive Saint-Gregoire

Radiotherapy, 6 Boulevard De La Boutiere, Cs 56816, Saint-Gregoire

Assistance Publique Hopitaux De Paris

Gastroenterology, 1 Avenue Claude Vellefaux, 75010, Paris

CHU Henri Mondor

Oncology, 1 rue Gustave Eiffel, 94010, Créteil Cedex

Centre Antoine Lacassagne

Oncology, 33 Avenue De Valombrose, 06189, Nice Cedex 2

Centre Hospitalier De Perpignan

Gastroenterology, 20 Avenue Du Languedoc, Cs 49954, Perpignan Cedex

Clinique De La Sauvegarde

Oncology, Avenue David Ben Gourion Lieudit, 69009, Lyon

Centre Hospitalier Annecy Genevois

Hepatogastroenterology, 1 Avenue De L Hopital, Bp 90074 Epagny Metz Tessy, Pringy Cedex

Centre Hospitalier Et Universitaire De Limoges

Oncology, 2 Avenue Martin Luther King, 87042, Limoges Cedex 1

Hôpital Avicenne

Hepatogastroenterology, 125 rue de Stalingrad, 93000, Bobigny

Centre Hospitalier D Avignon

Gastroenterology, 305 Rue Raoul Follereau, 84902, Avignon Cedex 9

Centre Hospitalier De Cholet

Oncology, 1 Rue De Marengo, 49300, Cholet

Centre Hospital Region Metz Thionville

Gastroenterology, 1 Allee Du Chateau, Cs 45001 Ars Laquenexy, Metz Cedex 03

Centre Hospitalier Universitaire Rouen

Gastroenterology, 1 Rue De Germont, Bp 96031, Rouen Cedex

Centre hospitalier de Lens

Oncology, 99 Bassée road, 62300, Lens

Assistance Publique Hopitaux De Paris

Oncology, 184 Rue Du Faubourg Saint Antoine, 75012, Paris

Centre Hospitalier Regional Universitaire De Tours

Gastroenterology, 49 Boulevard Beranger, 37000, Tours

Assistance Publique Hopitaux De Paris

Gastroenterology, 184 Rue Du Faubourg Saint Antoine, 75012, Paris

CHU Besancon

Oncology, 3 Boulevard Alexandre Fleming, 25000, Besancon

Hopital Prive Jean Mermoz

Gastroenterology, 55 Avenue Jean Mermoz, 69008, Lyon

Assistance Publique Hopitaux De Paris

Gastroenterology, Num Voie 47 A 83, 47 Boulevard De L Hopital, Paris

Centre Hospitalier Universitaire De Lille

Digestive surgery, 1 Place De Verdun, 59000, Lille

Hôpital Côte de Nacre - CHU de Caen

Hepato-gastroenterology and digestive oncology, Avenue de la côte de Nacre, 14033, Caen

Centre Eugène Marquis

Medical Oncology, Avenue de la Bataille de Flandres Dunkerque, 35000, Rennes

CHU St Etienne - Hôpital Nord

Hepato-gastroenterology and digestive oncology, Avenue Albert Raimond, 42270, Saint-Priest-en-Jarez

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country	Trial start	Trial end	Recruitment start	Recruitment end	Early termination
France	2024-09-24		2025-07-02

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 17 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Type	Title	Version
Protocol (for publication)	D1_Protocole AMPIRINOX 2024-511070-68-01	1.1
Recruitment arrangements (for publication)	K1_Recruiment arrangement	1
Subject information and informed consent form (for publication)	D4_Patient facing document questionnaire PAN26 French	1
Subject information and informed consent form (for publication)	D4_Patient facing document- questionnaire QLQ C30 French	1
Subject information and informed consent form (for publication)	D4_Patient facing document-treatment compliance diary	1
Subject information and informed consent form (for publication)	SIS and ICF AMPIRINOX 2024-511070-68-00	1.2
Subject information and informed consent form (for publication)	SIS and ICF AMPIRINOX 2024-511070-68-00-TC	1.2
Subject information and informed consent form (for publication)	SIS and ICF AMPIRINOX 2024-511070-68-00	1.1
Summary of Product Characteristics (SmPC) (for publication)	G2_ SmPC ELVORINE	1
Summary of Product Characteristics (SmPC) (for publication)	G2_ SmPC FLUOROURACILE PFIZER	1
Summary of Product Characteristics (SmPC) (for publication)	G2_ SmPC IRINOTECAN MEDAC	1
Summary of Product Characteristics (SmPC) (for publication)	G2_ SmPC OXALIPLATINE TEVA	1
Summary of Product Characteristics (SmPC) (for publication)	G2_SmPC CAPECITABINE ACCPORD	1
Summary of Product Characteristics (SmPC) (for publication)	G2_SmPC GEMCITABINE ACCORD	1
Synopsis of the protocol (for publication)	D1_Protocole synopsis_ENG AMPIRINOX 2024-511070-68-00	1.1
Synopsis of the protocol (for publication)	D1_Protocole synopsis_ENG AMPIRINOX 2024-511070-68-00 TC	1.1
Synopsis of the protocol (for publication)	D1_synopsis_ENG AMPIRINOX 2024-511070-68-01	1.0

Application history

3 submissions — initial application plus substantial / non-substantial modifications

#	Type	Code	Submitted	Reference MS	Conclusion	Decision date
1	INITIAL	IN	2024-07-25	France	Acceptable 2024-09-05	2024-09-24
2	SUBSTANTIAL MODIFICATION	SM-2	2025-03-21	France	Acceptable 2025-05-19	2025-05-26
3	SUBSTANTIAL MODIFICATION	SM-3	2025-08-08	France	Acceptable	2025-08-29