PHASE III RANDOMISED TRIAL to EVALUATE FOLFOX with or WITHOUT DOCETAXEL (TFOX) AS 1st LINE CHEMOTHERAPY for LOCALLY ADVANCED or METASTATIC OESOPHAGO-GASTRIC CARCINOMA
- Conditions
- OESOPHAGO-GASTRIC CARCINOMA
- Interventions
- Drug: 5Fluorouracil continuDrug: 5Fluorouracil bolus
- Registration Number
- NCT03006432
- Lead Sponsor
- Federation Francophone de Cancerologie Digestive
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 507
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description TFOX 5Fluorouracil continu Cycles every 15 days until progression desease FOLFOX Oxaliplatin Cycles every 15 days until progression desease FOLFOX 5Fluorouracil continu Cycles every 15 days until progression desease FOLFOX 5Fluorouracil bolus Cycles every 15 days until progression desease TFOX Oxaliplatin Cycles every 15 days until progression desease TFOX Docetaxel Cycles every 15 days until progression desease FOLFOX Folinic Acid Cycles every 15 days until progression desease TFOX Folinic Acid Cycles every 15 days until progression desease
- Primary Outcome Measures
Name Time Method progression-free survival 12 months after laste randomisation
- Secondary Outcome Measures
Name Time Method Objective response rate 12 months after laste randomisation Overall survival Toxicity events (adverse events) according to NCI-CTC v4.0 12 months after laste randomisation Toxicity events according to NCI-CTC v4.0 12 months after laste randomisation
Trial Locations
- Locations (130)
Institut Bergonie
🇫🇷Bordeaux CEDEX, France
CH de Blois
🇫🇷Blois, France
Hopital Saint Joseph -Saint Luc
🇫🇷Lyon, France
Plyclinique Saint Claude
🇫🇷Saint Quentin, France
HEGP
🇫🇷Paris, Ile de France, France
CH d'Abbeville
🇫🇷Abbeville CEDEX, France
CHU Amiens-Picardie
🇫🇷Amiens, France
CHU d'Angers
🇫🇷Angers CEDEX 9, France
Hôpital Privé D'Antony
🇫🇷Antony, France
Centre Hospitalier Victor Dupouy
🇫🇷Argenteuil, France
CH d'Auxerre
🇫🇷Auxerre, France
CH de la Côte Basque
🇫🇷Bayonne, France
CH
🇫🇷Senlis CEDEX, France
CH Germont et Gauthier
🇫🇷Bethune CEDEX, France
Centre Hospitalier Germon Et Gauthier
🇫🇷Bethune, France
Centre de Radiothérapie Pierre Curie
🇫🇷Beuvry, France
Polyclinique de Bordeaux Nord
🇫🇷Bordeaux CEDEX, France
Clinique Tivoli
🇫🇷Bordeaux, France
Polyclinique Saint Privat
🇫🇷Boujan-sur-Libron, France
Hôpital Duchenne
🇫🇷Boulogne Sur Mer, France
CMCO Côte d'Opale
🇫🇷Boulogne-sur-Mer, France
Centre Hospitalier Fleyriat
🇫🇷Bourg En Bresse, France
Centre Hospitalier Pierre Oudot
🇫🇷Bourgoin Jallieu, France
Hôpital Pierre Oudot
🇫🇷Bourgoin-Jallieu, France
CHU Côte de Nacre
🇫🇷Caen, France
CH William Morey
🇫🇷Chalon-sur-Saône, France
Infirmerie Protestante de Lyon
🇫🇷Caluire-et-Cuire, France
Médipôle de Savoie
🇫🇷Challes-les-Eaux, France
CH Metropole Savoie
🇫🇷Chambery, France
Centre Hospitalier William Morey
🇫🇷Chalon Sur Saone, France
Hopital Prive Paul D Engine
🇫🇷Champigny Sur Marne, France
Hopitaux de Chartres, Centre Hospitalier Louis Pasteur
🇫🇷Chartres, France
Clinique Saint Côme
🇫🇷Compiègne CEDEX, France
Centre Hospitalier Sud Francilien
🇫🇷Corbeil Essonnes, France
Clinique des Cèdres
🇫🇷Cornebarrieu, France
Centre Hospitalier Général
🇫🇷Châlons-en-Champagne, France
Hopital D Instruction Des Armées Percy
🇫🇷Clamart, France
Hopitaux civils de Colmar
🇫🇷Colmar, France
Centre Hospitalier de Cholet
🇫🇷Cholet, France
Groupe Hospitalier Du Sud de L'Oise
🇫🇷Creil, France
CHI
🇫🇷Creteil, France
Hôpital Henri Mondor
🇫🇷Créteil CEDEX, France
Institut de Cancérologie de Bourgogne - GRRECC
🇫🇷Dijon, France
Centre Georges-François Leclerc
🇫🇷Dijon, France
CHU
🇫🇷Dijon, France
CHI Elbeuf-Louvier-Val de Reuil
🇫🇷Elbeuf, France
Chu Claude Huriez
🇫🇷Lille, France
Clinique François Chénieux
🇫🇷Limoges, France
Centre Hospitalier de Dinan
🇫🇷Dinan, France
Centre Hospitalier Intercommunal Elbeuf-Louviers/Val de Reuil
🇫🇷Elbeuf, France
CHI de Fréjus Saint-Raphaël
🇫🇷Fréjus, France
Hôpital Jacques Monod
🇫🇷Flers CEDEX, France
GHM Institut Daniel Hollard
🇫🇷Grenoble CEDEX 1, France
Chu Albert Michallon
🇫🇷Grenoble, France
Hôpital privé Toulon/Hyères
🇫🇷Hyeres, France
CHD Vendée
🇫🇷La Roche-sur-Yon, France
CHU Grenoble - Hôpital Albert Michallon
🇫🇷La Tronche, France
Centre Hospitalier Emile Roux
🇫🇷Le Puy En Velay, France
Institut Hospitalier Franco-Britannique
🇫🇷Levallois Perret, France
CHU Dupuytren
🇫🇷Limoges, France
CH Longjumeau
🇫🇷Longjumeau, France
Clinique de la Sauvegarde
🇫🇷Lyon CEDEX 09, France
CHU de Lyon - Croix Rousse
🇫🇷Lyon, France
CH Saint Joseph - Saint Luc
🇫🇷Lyon, France
Centre Léon Berard
🇫🇷Lyon, France
Hôpital Edouard Herriot
🇫🇷Lyon, France
Hôpital Privé Jean Mermoz
🇫🇷Lyon, France
Centre Hospitalier Francois Quesnay
🇫🇷Mantes La Jolie, France
Hôpital Nord
🇫🇷Marseille CEDEX 20, France
CHU La Timone
🇫🇷Marseille CEDEX 5, France
Association Hopital Saint Joseph de Marseille
🇫🇷Marseille, France
Hôpital Européen
🇫🇷Marseille, France
Hopital Marc Jacquet
🇫🇷Melun, France
Ghi Le Raincy-Montfermeil
🇫🇷Montfermeil, France
Hôpital Monod
🇫🇷Montivilliers, France
Institut Régional du Cancer Montpellier
🇫🇷Montpellier, France
Centre Hospitalier
🇫🇷Pau CEDEX, France
Chu de Nancy
🇫🇷Nancy, France
Hôpital privé du Confluent SAS
🇫🇷Nantes, France
Chu de Nantes
🇫🇷Nantes, France
CH Pierre Bérégovoy
🇫🇷Nevers, France
CH de Niort
🇫🇷Niort, France
Hôpital de la source
🇫🇷Orléans CEDEX 2, France
CH Régional de la Source
🇫🇷Orléans, France
Hôpital Tenon
🇫🇷Paris CEDEX 20, France
CHU Cochin
🇫🇷Paris, France
Croix Saint Simon
🇫🇷Paris, France
Hôpital Saint Antoine
🇫🇷Paris, France
Centre Hospitalier Paris Saint Joseph
🇫🇷Paris, France
Groupe Hospitalier Pitié Salpêtrière
🇫🇷Paris, France
Hôpital Saint Louis
🇫🇷Paris, France
Institut Mutualiste Montsouris
🇫🇷Paris, France
Polyclinique Francheville
🇫🇷Perigueux, France
Centre Hospitalier Saint Jean
🇫🇷Perpignan, France
Hôpital Haut Leveque
🇫🇷Pessac CEDEX, France
CHU Lyon Sud
🇫🇷Pierre-Bénite CEDEX, France
Hôpital de la Milétrie
🇫🇷Poitiers, France
CH Annecy Genevois
🇫🇷Pringy, France
CHU Robert Debré
🇫🇷Reims CEDEX, France
Institut Jean Godinot
🇫🇷Reims, France
Centre Hospitalier de Romans Sur Isere
🇫🇷Romans Sur Isere, France
CHU Charles Nicolle
🇫🇷Rouen CEDEX 01, France
Chi Poissy Saint Germain
🇫🇷Saint Germain En Laye, France
Centre Hospitalier Prive Saint Gregoire
🇫🇷Saint Gregoire, France
Polyclinique Côte Basque
🇫🇷Saint Jean de Luz, France
Clinique de L Union
🇫🇷Saint Jean, France
Clinique de La Cote D Emeraude
🇫🇷Saint Malo, France
Clinique Mutualiste de L Estuaire
🇫🇷Saint Nazaire, France
Institut Lucien Neuwirth
🇫🇷Saint Priest En Jarez, France
Centre Hospitalier de Saint Malo
🇫🇷Saint-Malo, France
Centre Joliot Curie
🇫🇷Saint-Martin-Boulogne, France
CHU de Saint Etienne - Hôpital Nord
🇫🇷Saint-Priest-en-Jarez, France
Clinique Trenel
🇫🇷Sainte Colombe, France
Clinique Charcot
🇫🇷Sainte-foy-les-lyon, France
Centre de cancérologie
🇫🇷Sarcelles, France
Centre Hospitalier de Soissons
🇫🇷Soissons, France
Clinique Sainte Anne
🇫🇷Strasbourg, France
Centre Paul Strauss
🇫🇷Strasbourg, France
Les Hopitaux Universitaires de Strasbourg
🇫🇷Strasbourg, France
Hôpitaux du Leman
🇫🇷Thonon-les-Bains, France
Clinique Pasteur
🇫🇷Toulouse, France
Hôpital Trousseau
🇫🇷Tours CEDEX 9, France
Centre Hospitalier de Troyes
🇫🇷Troyes, France
entre Hospitalier
🇫🇷Valenciennes, France
CHU Nancy-Brabois
🇫🇷Vandœuvre-lès-Nancy, France
Centre Hospitalier Intercommunal
🇫🇷Villeneuve Saint Georges, France
Hôpital Privé de Villeneuve d'Asq
🇫🇷Villeneuve-d'Ascq, France
Medipole Hopital Mutualiste Lyon Villeurbanne
🇫🇷Villeurbanne, France
Chu Martinique
🇲🇶Fort de France, Martinique
CHU de Fort de France
🇲🇶Fort-de-France, Martinique