Informations générales (source: ClinicalTrials.gov)
ESSAI DE PHASE III RANDOMISE EVALUANT LE FOLFOX AVEC OU SANS DOCETAXEL (TFOX) EN 1ère LIGNE DE CHIMIOTHERAPIE DES ADENOCARCINOMES OESO-GASTRIQUES LOCALEMENT AVANCES OU METASTATIQUES (GASTFOX)
Interventional
Phase 3
Federation Francophone de Cancerologie Digestive (Voir sur ClinicalTrials)
décembre 2016
décembre 2025
09 juillet 2024
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.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CHI DE CRETEIL | Isabelle COJEAN-ZELEK | 29/03/2024 01:27:07 | Contacter | ||
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| AP-HP - Hôpital Cochin | Contact (sur clinicalTrials) | ||||
| AP-HP - Hôpital Henri Mondor-Albert Chenevier | Contact (sur clinicalTrials) | ||||
| AP-HP - Hôpital Saint Antoine | Contact (sur clinicalTrials) | ||||
| CENTRE HOSPITALIER SUD FRANCILIEN | Contact (sur clinicalTrials) | ||||
| GH PARIS SITE SAINT JOSEPH | Contact (sur clinicalTrials) | ||||
| GPE HOSP BROUSSAIS HEGP | Contact (sur clinicalTrials) | ||||
| HAD CROIX SAINT SIMON | Contact (sur clinicalTrials) | ||||
| IFSI AP-HP DE L'HÔPITAL TENON | Contact (sur clinicalTrials) | ||||
| IFSI DE L'HÔPITAL SAINT LOUIS | Contact (sur clinicalTrials) | ||||
| IFSI DU CH LONGJUMEAU | Contact (sur clinicalTrials) | ||||
| IFSI DU GROUPE HOSP. PITIÉ SALPÉTRIÈRE | Contact (sur clinicalTrials) | ||||
| INSTITUT MUTUALISTE MONTSOURIS | Contact (sur clinicalTrials) | ||||
| Les établissements hors Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Centre de cancérologie - 95200 - Sarcelles - France | Contact (sur clinicalTrials) | ||||
| Centre de Radiothérapie Pierre Curie - 62660 - Beuvry - France | Contact (sur clinicalTrials) | ||||
| Centre Georges-François Leclerc - 21079 - Dijon - France | Contact (sur clinicalTrials) | ||||
| Centre Hospitalier - 64046 - Pau CEDEX - France | Contact (sur clinicalTrials) | ||||
| Centre Hospitalier de Saint Malo - 35403 - Saint-Malo - France | Contact (sur clinicalTrials) | ||||
| Centre Hospitalier de Troyes - 10003 - Troyes CEDEX - France | Contact (sur clinicalTrials) | ||||
| Centre Hospitalier Général - 51005 - Châlons-en-Champagne - France | Contact (sur clinicalTrials) | ||||
| Centre Hospitalier Saint Jean - Perpignan - France | Contact (sur clinicalTrials) | ||||
| Centre Joliot Curie - 62280 - Saint-Martin-Boulogne - France | Contact (sur clinicalTrials) | ||||
| CH - 60309 - Senlis CEDEX - France | Contact (sur clinicalTrials) | ||||
| CH - Beauvais - France | Contact (sur clinicalTrials) | ||||
| CH Annecy Genevois - 74374 - Pringy - France | Contact (sur clinicalTrials) | ||||
| CH d'Abbeville - 80142 - Abbeville CEDEX - France | Contact (sur clinicalTrials) | ||||
| CH de Blois - 41000 - Blois - France | Contact (sur clinicalTrials) | ||||
| CH de la Côte Basque - Bayonne - France | Contact (sur clinicalTrials) | ||||
| CH Germont et Gauthier - 62408 - Bethune CEDEX - France | Contact (sur clinicalTrials) | ||||
| CH Metropole Savoie - Chambery - France | Contact (sur clinicalTrials) | ||||
| CH Pierre Bérégovoy - Nevers - France | Contact (sur clinicalTrials) | ||||
| CH Saint Joseph - Saint Luc - 69365 - Lyon - France | Contact (sur clinicalTrials) | ||||
| CH William Morey - 71100 - Chalon-sur-Saône - France | Contact (sur clinicalTrials) | ||||
| CHU - Dijon - France | Contact (sur clinicalTrials) | ||||
| CHU Charles Nicolle - 76031 - Rouen CEDEX 01 - France | Contact (sur clinicalTrials) | ||||
| CHU Côte de Nacre - 14033 - Caen - France | Contact (sur clinicalTrials) | ||||
| CHU d'Angers - 49933 - Angers CEDEX 9 - France | Contact (sur clinicalTrials) | ||||
| CHU de Lyon - Croix Rousse - 69317 - Lyon - France | Contact (sur clinicalTrials) | ||||
| CHU Dupuytren - 87042 - Limoges - France | Contact (sur clinicalTrials) | ||||
| CHU Grenoble - Hôpital Albert Michallon - 38700 - La Tronche - France | Contact (sur clinicalTrials) | ||||
| CHU La Timone - 13385 - Marseille CEDEX 5 - France | Contact (sur clinicalTrials) | ||||
| CHU Lyon Sud - Pierre-Bénite CEDEX - France | Contact (sur clinicalTrials) | ||||
| CHU Robert Debré - 51092 - Reims CEDEX - France | Contact (sur clinicalTrials) | ||||
| Clinique de la Sauvegarde - 69009 - Lyon CEDEX 09 - France | Contact (sur clinicalTrials) | ||||
| Clinique François Chénieux - 87000 - Limoges - France | Contact (sur clinicalTrials) | ||||
| Clinique Pasteur - 31300 - Toulouse - France | Contact (sur clinicalTrials) | ||||
| Clinique Saint Côme - 60204 - Compiègne CEDEX - France | Contact (sur clinicalTrials) | ||||
| Clinique Sainte Anne - 67000 - Strasbourg - France | Contact (sur clinicalTrials) | ||||
| Clinique Trenel - 69560 - Sainte Colombe - France | Contact (sur clinicalTrials) | ||||
| CMCO Côte d'Opale - 62222 - Boulogne-sur-Mer - France | Contact (sur clinicalTrials) | ||||
| GHM Institut Daniel Hollard - 38028 - Grenoble CEDEX 1 - France | Contact (sur clinicalTrials) | ||||
| Hôpital de la source - 45067 - Orléans CEDEX 2 - France | Contact (sur clinicalTrials) | ||||
| Hôpital Duchenne - Boulogne Sur Mer - France | Contact (sur clinicalTrials) | ||||
| Hôpital Européen - Marseille - France | Contact (sur clinicalTrials) | ||||
| Hôpital Haut Leveque - 33604 - Pessac CEDEX - France | Contact (sur clinicalTrials) | ||||
| Hôpital Monod - 76290 - Montivilliers - France | Contact (sur clinicalTrials) | ||||
| Hôpital Pierre Oudot - 38300 - Bourgoin-Jallieu - France | Contact (sur clinicalTrials) | ||||
| Hôpital Privé de Villeneuve d'Asq - Villeneuve-d'Ascq - France | Contact (sur clinicalTrials) | ||||
| Hôpital privé du Confluent SAS - 44277 - Nantes - France | Contact (sur clinicalTrials) | ||||
| Hôpital Privé Jean Mermoz - Lyon - France | Contact (sur clinicalTrials) | ||||
| Hopitaux civils de Colmar - 68024 - Colmar - France | Contact (sur clinicalTrials) | ||||
| Hôpitaux du Leman - 74203 - Thonon-les-Bains - France | Contact (sur clinicalTrials) | ||||
| Institut Bergonie - 33076 - Bordeaux CEDEX - France | Contact (sur clinicalTrials) | ||||
| Institut Jean Godinot - Reims - France | Contact (sur clinicalTrials) | ||||
| Institut Lucien Neuwirth - Saint Priest En Jarez - France | Contact (sur clinicalTrials) | ||||
| Institut Régional du Cancer Montpellier - 34298 - Montpellier - France | Contact (sur clinicalTrials) | ||||
| Médipôle de Savoie - 73190 - Challes-les-Eaux - France | Contact (sur clinicalTrials) | ||||
| Plyclinique Saint Claude - 02100 - Saint Quentin - France | Contact (sur clinicalTrials) | ||||
| Polyclinique Côte Basque - Saint Jean de Luz - France | Contact (sur clinicalTrials) | ||||
| Polyclinique Francheville - Perigueux - France | Contact (sur clinicalTrials) | ||||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Centre Hospitalier - 26216 - Montélimar - France | Contact (sur clinicalTrials) | ||||
| Centre Léon Berard - 69373 - Lyon - France | Contact (sur clinicalTrials) | ||||
| CH - Meaux - France | Contact (sur clinicalTrials) | ||||
| CH d'Auxerre - 89000 - Auxerre - France | Contact (sur clinicalTrials) | ||||
| CH de Niort - Niort - France | Contact (sur clinicalTrials) | ||||
| CH Régional de la Source - 45067 - Orléans - France | Contact (sur clinicalTrials) | ||||
| CHD Vendée - 85925 - La Roche-sur-Yon - France | Contact (sur clinicalTrials) | ||||
| CHI de Fréjus Saint-Raphaël - 83600 - Fréjus - France | Contact (sur clinicalTrials) | ||||
| CHI Elbeuf-Louvier-Val de Reuil - 76503 - Elbeuf - France | Contact (sur clinicalTrials) | ||||
| CHU Amiens-Picardie - Amiens - France | Contact (sur clinicalTrials) | ||||
| CHU de Saint Etienne - Hôpital Nord - 42270 - Saint-Priest-en-Jarez - France | Contact (sur clinicalTrials) | ||||
| CHU Nancy-Brabois - 54511 - Vandœuvre-lès-Nancy - France | Contact (sur clinicalTrials) | ||||
| Clinique des Cèdres - Cornebarrieu - France | Contact (sur clinicalTrials) | ||||
| Clinique Tivoli - 33000 - Bordeaux - France | Contact (sur clinicalTrials) | ||||
| entre Hospitalier - 59322 - Valenciennes - France | Contact (sur clinicalTrials) | ||||
| Hôpital de la Milétrie - 86021 - Poitiers - France | Contact (sur clinicalTrials) | ||||
| Hôpital Edouard Herriot - 69437 - Lyon - France | Contact (sur clinicalTrials) | ||||
| Hôpital Jacques Monod - 61104 - Flers CEDEX - France | Contact (sur clinicalTrials) | ||||
| Hôpital Nord - 13915 - Marseille CEDEX 20 - France | Contact (sur clinicalTrials) | ||||
| Hôpital Privé D'Antony - 92166 - Antony - France | Contact (sur clinicalTrials) | ||||
| Hôpital privé Toulon/Hyères - Hyeres - France | Contact (sur clinicalTrials) | ||||
| Hôpital Trousseau - 37044 - Tours CEDEX 9 - France | Contact (sur clinicalTrials) | ||||
| Infirmerie Protestante de Lyon - 69300 - Caluire-et-Cuire - France | Contact (sur clinicalTrials) | ||||
| Institut de Cancérologie de Bourgogne - GRRECC - 2100 - Dijon - France | Contact (sur clinicalTrials) | ||||
| Institut Hospitalier Franco-Britannique - Levallois Perret - France | Contact (sur clinicalTrials) | ||||
| Polyclinique de Bordeaux Nord - 33077 - Bordeaux CEDEX - France | Contact (sur clinicalTrials) | ||||
| Polyclinique Saint Privat - 34760 - Boujan-sur-Libron - France | Contact (sur clinicalTrials) | ||||
Critères
Tous
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
- 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
- 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