PHASE III RANDOMISED TRIAL to EVALUATE FOLFOX with or WITHOUT DOCETAXEL (TFOX) AS 1st LINE CHEMOTHERAPY for LOCALLY ADVANCED or METASTATIC OESOPHAGO-GASTRIC CARCINOMA

NCT ID: NCT03006432

Last Updated: 2025-03-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

507 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-12-19

Study Completion Date

2025-02-27

Brief Summary

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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.

Detailed Description

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Conditions

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OESOPHAGO-GASTRIC CARCINOMA

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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FOLFOX

Cycles every 15 days until progression desease

Group Type ACTIVE_COMPARATOR

Oxaliplatin

Intervention Type DRUG

5Fluorouracil bolus

Intervention Type DRUG

5Fluorouracil continu

Intervention Type DRUG

Folinic Acid

Intervention Type DRUG

TFOX

Cycles every 15 days until progression desease

Group Type EXPERIMENTAL

Oxaliplatin

Intervention Type DRUG

5Fluorouracil continu

Intervention Type DRUG

Docetaxel

Intervention Type DRUG

Folinic Acid

Intervention Type DRUG

Interventions

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Oxaliplatin

Intervention Type DRUG

5Fluorouracil bolus

Intervention Type DRUG

5Fluorouracil continu

Intervention Type DRUG

Docetaxel

Intervention Type DRUG

Folinic Acid

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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
* Women of childbearing age and men (who are in a sexual relationship with women of childbearing age) must agree to use effective contraception without interruption for the duration of the treatment and for 6 months after administration of the last dose of treatment
* Patient affiliated to a social security scheme
* Patient information and signature of informed consent form

Exclusion Criteria

* 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
* Persons in custody or under wardship
* Impossibility of undergoing medical monitoring during the trial for geographical, social or psychological reasons
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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UNICANCER

OTHER

Sponsor Role collaborator

GERCOR - Multidisciplinary Oncology Cooperative Group

OTHER

Sponsor Role collaborator

Federation Francophone de Cancerologie Digestive

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Aziz ZAANAN

Role: STUDY_CHAIR

HEGP, Paris

Locations

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CH d'Abbeville

Abbeville, , France

Site Status

CHU Amiens-Picardie

Amiens, , France

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CHU d'Angers

Angers, , France

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Hôpital Privé D'Antony

Antony, , France

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Centre Hospitalier Victor Dupouy

Argenteuil, , France

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CH d'Auxerre

Auxerre, , France

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CH de la Côte Basque

Bayonne, , France

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CH

Beauvais, , France

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Centre de Radiothérapie Pierre Curie

Beuvry, , France

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CH Germont et Gauthier

Béthune, , France

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Centre Hospitalier Germon Et Gauthier

Béthune, , France

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CH de Blois

Blois, , France

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Clinique Tivoli

Bordeaux, , France

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Institut Bergonie

Bordeaux, , France

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Polyclinique de Bordeaux Nord

Bordeaux, , France

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Polyclinique Saint Privat

Boujan-sur-Libron, , France

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CMCO Côte d'Opale

Boulogne-sur-Mer, , France

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Hôpital Duchenne

Boulogne-sur-Mer, , France

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Centre Hospitalier Fleyriat

Bourg-en-Bresse, , France

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Hôpital Pierre Oudot

Bourgoin, , France

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Centre Hospitalier Pierre Oudot

Bourgoin, , France

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CHU Côte de Nacre

Caen, , France

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Infirmerie Protestante de Lyon

Caluire-et-Cuire, , France

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Médipôle de Savoie

Challes-les-Eaux, , France

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CH William Morey

Chalon-sur-Saône, , France

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Centre Hospitalier William Morey

Chalon-sur-Saône, , France

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CH Metropole Savoie

Chambéry, , France

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Hopital Prive Paul D Engine

Champigny-sur-Marne, , France

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Hopitaux de Chartres, Centre Hospitalier Louis Pasteur

Chartres, , France

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Centre Hospitalier Général

Châlons-en-Champagne, , France

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Centre Hospitalier de Cholet

Cholet, , France

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Hopital D Instruction Des Armées Percy

Clamart, , France

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Hopitaux civils de Colmar

Colmar, , France

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Clinique Saint Côme

Compiègne, , France

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Centre Hospitalier Sud Francilien

Corbeil-Essonnes, , France

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Clinique des Cèdres

Cornebarrieu, , France

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Groupe Hospitalier Du Sud de L'Oise

Creil, , France

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Hôpital Henri Mondor

Créteil, , France

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CHI

Créteil, , France

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Institut de Cancérologie de Bourgogne - GRRECC

Dijon, , France

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Centre Georges-François Leclerc

Dijon, , France

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CHU

Dijon, , France

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Centre Hospitalier de Dinan

Dinan, , France

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CHI Elbeuf-Louvier-Val de Reuil

Elbeuf, , France

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Centre Hospitalier Intercommunal Elbeuf-Louviers/Val de Reuil

Elbeuf, , France

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Hôpital Jacques Monod

Flers, , France

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CHI de Fréjus Saint-Raphaël

Fréjus, , France

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GHM Institut Daniel Hollard

Grenoble, , France

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Chu Albert Michallon

Grenoble, , France

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Hôpital privé Toulon/Hyères

Hyères, , France

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CHD Vendée

La Roche-sur-Yon, , France

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CHU Grenoble - Hôpital Albert Michallon

La Tronche, , France

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Centre Hospitalier Emile Roux

Le Puy-en-Velay, , France

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Institut Hospitalier Franco-Britannique

Levallois-Perret, , France

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Chu Claude Huriez

Lille, , France

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Clinique François Chénieux

Limoges, , France

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CHU Dupuytren

Limoges, , France

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CH Longjumeau

Longjumeau, , France

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Clinique de la Sauvegarde

Lyon, , France

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CHU de Lyon - Croix Rousse

Lyon, , France

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CH Saint Joseph - Saint Luc

Lyon, , France

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Centre Léon Berard

Lyon, , France

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Hôpital Edouard Herriot

Lyon, , France

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Hopital Saint Joseph -Saint Luc

Lyon, , France

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Hôpital Privé Jean Mermoz

Lyon, , France

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Centre Hospitalier Francois Quesnay

Mantes-la-Jolie, , France

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CHU La Timone

Marseille, , France

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Hôpital Nord

Marseille, , France

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Association Hopital Saint Joseph de Marseille

Marseille, , France

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Hôpital Européen

Marseille, , France

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CH

Meaux, , France

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Hopital Marc Jacquet

Melun, , France

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Centre Hospitalier

Montélimar, , France

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Ghi Le Raincy-Montfermeil

Montfermeil, , France

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Hôpital Monod

Montivilliers, , France

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Institut Régional du Cancer Montpellier

Montpellier, , France

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Chu de Nancy

Nancy, , France

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Hôpital privé du Confluent SAS

Nantes, , France

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Chu de Nantes

Nantes, , France

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CH Pierre Bérégovoy

Nevers, , France

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CH de Niort

Niort, , France

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CH Régional de la Source

Orléans, , France

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Hôpital de la source

Orléans, , France

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CHU Cochin

Paris, , France

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Croix Saint Simon

Paris, , France

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Hôpital Saint Antoine

Paris, , France

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Hôpital Tenon

Paris, , France

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Centre Hospitalier Paris Saint Joseph

Paris, , France

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Groupe Hospitalier Pitié Salpêtrière

Paris, , France

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Hôpital Saint Louis

Paris, , France

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Institut Mutualiste Montsouris

Paris, , France

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Centre Hospitalier

Pau, , France

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Centre Hospitalier Saint Jean

Perpignan, , France

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Hôpital Haut Leveque

Pessac, , France

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Polyclinique Francheville

Périgueux, , France

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CHU Lyon Sud

Pierre-Bénite, , France

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Hôpital de la Milétrie

Poitiers, , France

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CH Annecy Genevois

Pringy, , France

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CHU Robert Debré

Reims, , France

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Institut Jean Godinot

Reims, , France

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Centre Hospitalier de Romans Sur Isere

Romans-sur-Isère, , France

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CHU Charles Nicolle

Rouen, , France

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Chi Poissy Saint Germain

Saint-Germain-en-Laye, , France

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Centre Hospitalier Prive Saint Gregoire

Saint-Grégoire, , France

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Clinique de L Union

Saint-Jean, , France

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Polyclinique Côte Basque

Saint-Jean-de-Luz, , France

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Centre Joliot Curie

Saint-Martin-Boulogne, , France

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Clinique Mutualiste de L Estuaire

Saint-Nazaire, , France

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CHU de Saint Etienne - Hôpital Nord

Saint-Priest-en-Jarez, , France

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Institut Lucien Neuwirth

Saint-Priest-en-Jarez, , France

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Plyclinique Saint Claude

Saint-Quentin, , France

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Clinique Trenel

Sainte-Colombe, , France

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Clinique Charcot

Sainte-Foy-lès-Lyon, , France

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Centre de cancérologie

Sarcelles, , France

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CH

Senlis, , France

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Centre Hospitalier de Soissons

Soissons, , France

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Centre Hospitalier de Saint Malo

St-Malo, , France

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Clinique de La Cote D Emeraude

St-Malo, , France

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Clinique Sainte Anne

Strasbourg, , France

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Centre Paul Strauss

Strasbourg, , France

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Les Hopitaux Universitaires de Strasbourg

Strasbourg, , France

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Hôpitaux du Leman

Thonon-les-Bains, , France

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Clinique Pasteur

Toulouse, , France

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Hôpital Trousseau

Tours, , France

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Centre Hospitalier de Troyes

Troyes, , France

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Centre Hospitalier de Troyes

Troyes, , France

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entre Hospitalier

Valenciennes, , France

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CHU Nancy-Brabois

Vandœuvre-lès-Nancy, , France

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Hôpital Privé de Villeneuve d'Asq

Villeneuve-d'Ascq, , France

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Centre Hospitalier Intercommunal

Villeneuve-Saint-Georges, , France

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Medipole Hopital Mutualiste Lyon Villeurbanne

Villeurbanne, , France

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HEGP

Paris, Île-de-France Region, France

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CHU de Fort de France

Fort-de-France, , Martinique

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Chu Martinique

Fort-de-France, , Martinique

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Countries

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France Martinique

References

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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.

Reference Type BACKGROUND
PMID: 29409778 (View on PubMed)

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.

Reference Type DERIVED
PMID: 40286809 (View on PubMed)

Other Identifiers

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PRODIGE 51

Identifier Type: -

Identifier Source: org_study_id

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