NCT03006432

Brief Summary

Gastric cancer is the fourth commonest cancer and the second largest cause of mortality from cancer. Surgical resection of localised forms of gastric cancer offers the only chance of a cure. The vast majority of patients, however, present with advanced disease from the outset (locally advanced or metastatic) or recurrent after resection of a localised form. For metastatic or locally advanced stages of gastric or gastro-oesophageal junction adenocarcinoma, the combination of 2 chemotherapy drugs (dual therapy) as compared with monotherapy or no chemotherapy, makes it possible to improve the tumour response and patient survival. Dual therapy comprising cisplatin + fluoropyrimidine (CF protocol) is considered as one of the first-line chemotherapy treatment standards. The addition of docetaxel to the CF regime (referred to as the DCF protocol) has made it possible to improve the tumour response rate, the time to tumour progression and overall survival in a randomised phase III trial. This improvement in treatment efficacy was achieved, however, at the expense of a significant increase in grade 3-4 toxicity, including diarrhoea , neutropenia, and neutropenia with complications. Although DCF is considered as a therapeutic standard for advanced forms of gastric cancer, its use is limited in clinical practice due to its high toxicity. Oxaliplatin has shown its usefulness in treatment of oesophagogastric cancer, with an efficacy at least equal to that of cisplatin. Peripheral sensory neuropathy was less common in the 5FU-cisplatin arm. In terms of treatment efficacy, 5FU-oxaliplatin versus 5FU-cisplatin was associated with a non-significant improvement in median progression free survival rates, and overall survival. All these data thus suggest that 5FU-oxaliplatin is at least as efficacious and is better tolerated than 5FU-cisplatin, and also that docetaxel-5FU-cisplatin is more efficacious than 5FU-cisplatin, with limited use due to its high toxicity. In the logical continuation of development of chemotherapy protocols for metastatic gastric cancer, the question therefore arises of the usefulness of adding docetaxel to 5FU-oxaliplatin, in terms of efficacy and also tolerance. In France, chemotherapy with FOLFOX is used extensively as a first line of treatment in advanced gastric cancer, but with progression-free survival and median survival rates that are still too low, and a poor response rate. The use of docetaxel at a dose of 50 mg/m2 every 2 weeks in combination with FOLFOX (TFOX protocol) has shown very interesting results in phase II studies in terms of efficacy and tolerability, and these are worth confirming through a phase III randomised trial. In fact, if these results are confirmed in phase III, TFOX could become the new first-line therapeutic standard for advanced gastric cancer, while limiting toxicity and preserving patients' quality of life, and could become the reference treatment to accompany the targeted therapies currently being developed for this disease. The primary objective of this randomised phase III trial is to compare the progression-free survival on dual therapy with 5FU-oxaliplatin (FOLFOX protocol) with triple therapy with 5FU-oxaliplatin-docetaxel (TFOX protocol) in treatment of advanced forms of gastric or oesophagogastric junction adenocarcinoma. The secondary objectives are overall survival, the tumour response rate, toxicity, quality of life and the therapeutic index, defined as the ratio between the median progression-free survival and the febrile neutropenia rate.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
507

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Dec 2016

Longer than P75 for phase_3

Geographic Reach
2 countries

134 active sites

Status
completed

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

Study Start

First participant enrolled

December 19, 2016

Completed
8 days until next milestone

First Submitted

Initial submission to the registry

December 27, 2016

Completed
3 days until next milestone

First Posted

Study publicly available on registry

December 30, 2016

Completed
8.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 27, 2025

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 27, 2025

Completed
Last Updated

March 5, 2025

Status Verified

January 1, 2025

Enrollment Period

8.2 years

First QC Date

December 27, 2016

Last Update Submit

March 3, 2025

Conditions

Keywords

OESOPHAGO-GASTRIC CARCINOMA

Outcome Measures

Primary Outcomes (1)

  • progression-free survival

    12 months after laste randomisation

Secondary Outcomes (3)

  • Overall survival Toxicity events (adverse events) according to NCI-CTC v4.0

    12 months after laste randomisation

  • Objective response rate

    12 months after laste randomisation

  • Toxicity events according to NCI-CTC v4.0

    12 months after laste randomisation

Study Arms (2)

FOLFOX

ACTIVE COMPARATOR

Cycles every 15 days until progression desease

Drug: OxaliplatinDrug: 5Fluorouracil bolusDrug: 5Fluorouracil continuDrug: Folinic Acid

TFOX

EXPERIMENTAL

Cycles every 15 days until progression desease

Drug: OxaliplatinDrug: 5Fluorouracil continuDrug: DocetaxelDrug: Folinic Acid

Interventions

FOLFOXTFOX
FOLFOXTFOX
TFOX
FOLFOXTFOX

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Gastric or gastro-oesophageal junction adenocarcinoma (all Siewert), histologically proven (on primary tumour or metastatic lesion),
  • HER2 negative (positive HER2 status is defined by a positive IHC test of 3+ or IHC of 2+ with positive FISH)
  • Metastatic or non-resectable (locally advanced) disease
  • Disease measurable according to RECIST v1.1 criteria (at least one measurable lesion)
  • No major surgical procedure during the 4 weeks prior to randomisation:
  • Patient eligible for a 1st line of chemotherapy based on 5FU, folinic acid and oxaliplatin (FOLFOX) with or without docetaxel (TFOX)
  • WHO: 0-1
  • Age ≥ 18
  • BMI \> 18
  • Life expectancy \> 3 months
  • PNN \> 1500/mm3, platelets \> 100,000/mm3, Hb \> 10 g/dL
  • AST, ALT ≤ 3.5 times the UNL, alkaline phosphatase \< 6 times the UNL
  • Bilirubin ≤ 1.5 times the UNL,
  • Creatinine clearance according to Cockcroft and Gault formula \> 50 mL/min
  • Women of childbearing age must have a negative pregnancy test (β HCG) before starting treatment
  • +3 more criteria

You may not qualify if:

  • Presence of cerebral or meningeal metastases
  • Presence of \> grade 2 neuropathy according to NCIC-CTC 4.0
  • Known DPD deficiency
  • QT/QTc interval \> 450 msec for men and \> 470 msec for women
  • K+ \< LNL, Mg2+ \< LNL, Ca2+ \< LNL
  • Any known specific contraindication or allergy to the treatments used in the study (cf RCP Appendix 7)
  • Chemotherapy or radio-chemotherapy in an adjuvant situation finished less than 12 months ago
  • Prior chemotherapy including oxaliplatin (except for adjuvant chemotherapy)
  • Prior chemotherapy including docetaxel
  • Any progressive pathology not stabilised over the past 6 months: liver impairment, renal impairment, respiratory or cardiac failure
  • HIV+ patients
  • Radiotherapy during the 4 weeks prior to randomisation
  • Other concomitant cancer or a history of cancer during the previous 5 years, with the exception of carcinoma in situ of the cervix or basal cell carcinoma or epidermoid cell carcinoma of the skin which is considered to be cured
  • Patient already included in another clinical trial involving an experimental drug
  • Pregnant or breastfeeding woman
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (134)

CH d'Abbeville

Abbeville, 80142, France

Location

CHU Amiens-Picardie

Amiens, France

Location

CHU d'Angers

Angers, 49933, France

Location

Hôpital Privé D'Antony

Antony, 92166, France

Location

Centre Hospitalier Victor Dupouy

Argenteuil, France

Location

CH d'Auxerre

Auxerre, 89000, France

Location

CH de la Côte Basque

Bayonne, France

Location

CH

Beauvais, France

Location

Centre de Radiothérapie Pierre Curie

Beuvry, 62660, France

Location

CH Germont et Gauthier

Béthune, 62408, France

Location

Centre Hospitalier Germon Et Gauthier

Béthune, France

Location

CH de Blois

Blois, 41000, France

Location

Clinique Tivoli

Bordeaux, 33000, France

Location

Institut Bergonie

Bordeaux, 33076, France

Location

Polyclinique de Bordeaux Nord

Bordeaux, 33077, France

Location

Polyclinique Saint Privat

Boujan-sur-Libron, 34760, France

Location

CMCO Côte d'Opale

Boulogne-sur-Mer, 62222, France

Location

Hôpital Duchenne

Boulogne-sur-Mer, France

Location

Centre Hospitalier Fleyriat

Bourg-en-Bresse, France

Location

Hôpital Pierre Oudot

Bourgoin, 38300, France

Location

Centre Hospitalier Pierre Oudot

Bourgoin, France

Location

CHU Côte de Nacre

Caen, 14033, France

Location

Infirmerie Protestante de Lyon

Caluire-et-Cuire, 69300, France

Location

Médipôle de Savoie

Challes-les-Eaux, 73190, France

Location

CH William Morey

Chalon-sur-Saône, 71100, France

Location

Centre Hospitalier William Morey

Chalon-sur-Saône, France

Location

CH Metropole Savoie

Chambéry, France

Location

Hopital Prive Paul D Engine

Champigny-sur-Marne, France

Location

Hopitaux de Chartres, Centre Hospitalier Louis Pasteur

Chartres, France

Location

Centre Hospitalier Général

Châlons-en-Champagne, 51005, France

Location

Centre Hospitalier de Cholet

Cholet, France

Location

Hopital D Instruction Des Armées Percy

Clamart, France

Location

Hopitaux civils de Colmar

Colmar, 68024, France

Location

Clinique Saint Côme

Compiègne, 60204, France

Location

Centre Hospitalier Sud Francilien

Corbeil-Essonnes, France

Location

Clinique des Cèdres

Cornebarrieu, France

Location

Groupe Hospitalier Du Sud de L'Oise

Creil, France

Location

Hôpital Henri Mondor

Créteil, 94000, France

Location

CHI

Créteil, France

Location

Institut de Cancérologie de Bourgogne - GRRECC

Dijon, 2100, France

Location

Centre Georges-François Leclerc

Dijon, 21079, France

Location

CHU

Dijon, France

Location

Centre Hospitalier de Dinan

Dinan, France

Location

CHI Elbeuf-Louvier-Val de Reuil

Elbeuf, 76503, France

Location

Centre Hospitalier Intercommunal Elbeuf-Louviers/Val de Reuil

Elbeuf, France

Location

Hôpital Jacques Monod

Flers, 61104, France

Location

CHI de Fréjus Saint-Raphaël

Fréjus, 83600, France

Location

GHM Institut Daniel Hollard

Grenoble, 38028, France

Location

Chu Albert Michallon

Grenoble, France

Location

Hôpital privé Toulon/Hyères

Hyères, France

Location

CHD Vendée

La Roche-sur-Yon, 85925, France

Location

CHU Grenoble - Hôpital Albert Michallon

La Tronche, 38700, France

Location

Centre Hospitalier Emile Roux

Le Puy-en-Velay, France

Location

Institut Hospitalier Franco-Britannique

Levallois-Perret, France

Location

Chu Claude Huriez

Lille, France

Location

Clinique François Chénieux

Limoges, 87000, France

Location

CHU Dupuytren

Limoges, 87042, France

Location

CH Longjumeau

Longjumeau, 91160, France

Location

Clinique de la Sauvegarde

Lyon, 69009, France

Location

CHU de Lyon - Croix Rousse

Lyon, 69317, France

Location

CH Saint Joseph - Saint Luc

Lyon, 69365, France

Location

Centre Léon Berard

Lyon, 69373, France

Location

Hôpital Edouard Herriot

Lyon, 69437, France

Location

Hopital Saint Joseph -Saint Luc

Lyon, France

Location

Hôpital Privé Jean Mermoz

Lyon, France

Location

Centre Hospitalier Francois Quesnay

Mantes-la-Jolie, France

Location

CHU La Timone

Marseille, 13385, France

Location

Hôpital Nord

Marseille, 13915, France

Location

Association Hopital Saint Joseph de Marseille

Marseille, France

Location

Hôpital Européen

Marseille, France

Location

CH

Meaux, France

Location

Hopital Marc Jacquet

Melun, France

Location

Centre Hospitalier

Montélimar, 26216, France

Location

Ghi Le Raincy-Montfermeil

Montfermeil, France

Location

Hôpital Monod

Montivilliers, 76290, France

Location

Institut Régional du Cancer Montpellier

Montpellier, 34298, France

Location

Chu de Nancy

Nancy, France

Location

Hôpital privé du Confluent SAS

Nantes, 44277, France

Location

Chu de Nantes

Nantes, France

Location

CH Pierre Bérégovoy

Nevers, France

Location

CH de Niort

Niort, France

Location

CH Régional de la Source

Orléans, 45067, France

Location

Hôpital de la source

Orléans, 45067, France

Location

CHU Cochin

Paris, 75014, France

Location

Croix Saint Simon

Paris, 75020, France

Location

Hôpital Saint Antoine

Paris, 75571, France

Location

Hôpital Tenon

Paris, 75970, France

Location

Centre Hospitalier Paris Saint Joseph

Paris, France

Location

Groupe Hospitalier Pitié Salpêtrière

Paris, France

Location

Hôpital Saint Louis

Paris, France

Location

Institut Mutualiste Montsouris

Paris, France

Location

Centre Hospitalier

Pau, 64046, France

Location

Centre Hospitalier Saint Jean

Perpignan, France

Location

Hôpital Haut Leveque

Pessac, 33604, France

Location

Polyclinique Francheville

Périgueux, France

Location

CHU Lyon Sud

Pierre-Bénite, France

Location

Hôpital de la Milétrie

Poitiers, 86021, France

Location

CH Annecy Genevois

Pringy, 74374, France

Location

CHU Robert Debré

Reims, 51092, France

Location

Institut Jean Godinot

Reims, France

Location

Centre Hospitalier de Romans Sur Isere

Romans-sur-Isère, France

Location

CHU Charles Nicolle

Rouen, 76031, France

Location

Chi Poissy Saint Germain

Saint-Germain-en-Laye, France

Location

Centre Hospitalier Prive Saint Gregoire

Saint-Grégoire, France

Location

Clinique de L Union

Saint-Jean, France

Location

Polyclinique Côte Basque

Saint-Jean-de-Luz, France

Location

Centre Joliot Curie

Saint-Martin-Boulogne, 62280, France

Location

Clinique Mutualiste de L Estuaire

Saint-Nazaire, France

Location

CHU de Saint Etienne - Hôpital Nord

Saint-Priest-en-Jarez, 42270, France

Location

Institut Lucien Neuwirth

Saint-Priest-en-Jarez, France

Location

Plyclinique Saint Claude

Saint-Quentin, 02100, France

Location

Clinique Trenel

Sainte-Colombe, 69560, France

Location

Clinique Charcot

Sainte-Foy-lès-Lyon, France

Location

Centre de cancérologie

Sarcelles, 95200, France

Location

CH

Senlis, 60309, France

Location

Centre Hospitalier de Soissons

Soissons, France

Location

Centre Hospitalier de Saint Malo

St-Malo, 35403, France

Location

Clinique de La Cote D Emeraude

St-Malo, France

Location

Clinique Sainte Anne

Strasbourg, 67000, France

Location

Centre Paul Strauss

Strasbourg, France

Location

Les Hopitaux Universitaires de Strasbourg

Strasbourg, France

Location

Hôpitaux du Leman

Thonon-les-Bains, 74203, France

Location

Clinique Pasteur

Toulouse, 31300, France

Location

Hôpital Trousseau

Tours, 37044, France

Location

Centre Hospitalier de Troyes

Troyes, 10003, France

Location

Centre Hospitalier de Troyes

Troyes, France

Location

entre Hospitalier

Valenciennes, 59322, France

Location

CHU Nancy-Brabois

Vandœuvre-lès-Nancy, 54511, France

Location

Hôpital Privé de Villeneuve d'Asq

Villeneuve-d'Ascq, France

Location

Centre Hospitalier Intercommunal

Villeneuve-Saint-Georges, France

Location

Medipole Hopital Mutualiste Lyon Villeurbanne

Villeurbanne, France

Location

HEGP

Paris, Île-de-France Region, 75015, France

Location

CHU de Fort de France

Fort-de-France, 97261, Martinique

Location

Chu Martinique

Fort-de-France, Martinique

Location

Related Publications (2)

  • Zaanan A, Samalin E, Aparicio T, Bouche O, Laurent-Puig P, Manfredi S, Michel P, Monterymard C, Moreau M, Rougier P, Tougeron D, Taieb J, Louvet C. Phase III randomized trial comparing 5-fluorouracil and oxaliplatin with or without docetaxel in first-line advanced gastric cancer chemotherapy (GASTFOX study). Dig Liver Dis. 2018 Apr;50(4):408-410. doi: 10.1016/j.dld.2018.01.119. Epub 2018 Mar 1.

    PMID: 29409778BACKGROUND
  • Zaanan A, Bouche O, de la Fouchardiere C, Le Malicot K, Pernot S, Louvet C, Artru P, Le Brun Ly V, Aldabbagh K, Khemissa-Akouz F, Lecomte T, Castanie H, Laly M, Botsen D, Roth G, Samalin E, Muller M, Breysacher G, Manfredi S, Phelip JM, Taieb J. TFOX versus FOLFOX in first-line treatment of patients with advanced HER2-negative gastric or gastro-oesophageal junction adenocarcinoma (PRODIGE 51- FFCD-GASTFOX): an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2025 Jun;26(6):732-744. doi: 10.1016/S1470-2045(25)00130-5. Epub 2025 Apr 23.

MeSH Terms

Interventions

OxaliplatinDocetaxelLeucovorin

Intervention Hierarchy (Ancestors)

Coordination ComplexesOrganic ChemicalsTaxoidsCyclodecanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsDiterpenesTerpenesFormyltetrahydrofolatesTetrahydrofolatesFolic AcidPterinsPteridinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsCoenzymesEnzymes and Coenzymes

Study Officials

  • Aziz ZAANAN

    HEGP, Paris

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 27, 2016

First Posted

December 30, 2016

Study Start

December 19, 2016

Primary Completion

February 27, 2025

Study Completion

February 27, 2025

Last Updated

March 5, 2025

Record last verified: 2025-01

Data Sharing

IPD Sharing
Will not share

Locations