Randomised Study Evaluating Adjuvant Chemotherapy After Resection of Stage III Colonic Adenocarcinoma in Patients of 70 and Over

Colonic Adenocarcinoma Clinical Trial

— ADAGE  

Official title:

Randomised Phase III Study Evaluating Adjuvant Chemotherapy After Resection of Stage III Colonic Adenocarcinoma in Patients of 70 and Over Intergroup Trial: Ffcd, Gercor, Gerico, Unicancer-gi

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02355379
• Other study ID #: PRODIGE34-ADAGE
• Status: Recruiting
• Phase: Phase 3
• Start date: January 2015
• Est. completion date: August 2025

Study information

• Verified date: August 2023
• Source: Federation Francophone de Cancerologie Digestive
• Contact: Martina Schneider
• Phone: +33 3 80 39 34 83
• Email: martina.schneider[@]u-bourgogne.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Colorectal cancer occurs mainly in elderly patients. Recent estimation showed that in France more than 50% of the patients diagnosed with a colorectal cancer are 70 years old or more. Adjuvant chemotherapy has demonstrated a benefit on disease-free survival and overall survival after a stage III colon cancer resection. Nevertheless adjuvant chemotherapy is poorly used in elderly patients. Prognostic improvement with chemotherapy based on 5FU is suggested by a post-hoc analysis of randomized prospective clinical trial. But elderly patients in this study were highly selected and patients older than 80 represented only 0.7% of the total population. Thus, there is still a concern about the benefit of adjuvant 5FU-based chemotherapy in very elderly unselected patients.

The recommended treatment for stage III adjuvant chemotherapy is a combination of fuoropyrimidine and oxaliplatin. Nevertheless oxaliplatin did not demonstrated survival advantage in elderly patients.

Altogether there are still two matters of debate:

• First, is there a benefit of fluoropyrimidine-based adjuvant chemotherapy for unfit elderly patients?

• Second, is there a benefit of oxaliplatin-based adjuvant chemotherapy for fit elderly patients? The aim of this randomized phase III study is to evaluate the benefit for disease-free survival of adjuvant chemotherapy in elderly patient and which chemotherapy.

The elderly patient population will be dichotomized into two groups according to physician's choice after a multidisciplinary evaluation involving a geriatrician, with two different randomization assignments. The patients with an expected life-expectancy below 4 years according Lee score are excluded of this study.

Some biological tumour abnormalities are more frequently observed in elderly (i.e. mismatch repair deficiency), therefore an evaluation of specific biological prognostic factors is needed in elderly population.

Description:

Colorectal cancer occurs mainly in elderly patients. Recent estimation showed that in France more than 50% of the patients diagnosed with a colorectal cancer are 70 years old or more. Adjuvant chemotherapy has demonstrated a benefit on disease-free survival and overall survival after a stage III colon cancer resection. Nevertheless adjuvant chemotherapy is poorly used in elderly patients. Prognostic improvement with chemotherapy based on 5FU is suggested by a post-hoc analysis of randomized prospective clinical trial. But elderly patients in this study were highly selected and patients older than 80 represented only 0.7% of the total population. Thus, there is still a concern about the benefit of adjuvant 5FU-based chemotherapy in very elderly unselected patients.

The recommended treatment for stage III adjuvant chemotherapy is a combination of fuoropyrimidine and oxaliplatin. Nevertheless oxaliplatin did not demonstrated survival advantage in elderly patients.

Altogether there are still two matters of debate:

• First, is there a benefit of fluoropyrimidine-based adjuvant chemotherapy for unfit elderly patients?

• Second, is there a benefit of oxaliplatin-based adjuvant chemotherapy for fit elderly patients? The aim of this randomized phase III study is to evaluate the benefit for disease-free survival of adjuvant chemotherapy in elderly patient and which chemotherapy.

The elderly patient population will be dichotomized into two groups according to physician's choice after a multidisciplinary evaluation involving a geriatrician, with two different randomization assignments. The patients with an expected life-expectancy below 4 years according Lee score are excluded of this study.

Some biological tumour abnormalities are more frequently observed in elderly (i.e. mismatch repair deficiency), therefore an evaluation of specific biological prognostic factors is needed in elderly population.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 774
• Est. completion date: August 2025
• Est. primary completion date: February 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 75 Years and older

Eligibility

Inclusion Criteria:

• Age = 70 years

• Patient considered able to receive chemotherapy

• Lee score detailed faxed to CRGA

• Stage III colon adenocarcinoma

• R0 resection of the primary tumor

• Start of the potential adjuvant chemotherapy within 12 weeks after surgery

• No prior chemotherapy for colon cancer

• Geriatric Self-administered questionnaire completed faxed to CRGA

• Geriatric Questionnaire completed by the team faxed to CRGA

• Effective contraception for men patients throughout treatment and for at least 6 months after discontinuation of oxaliplatin

• Consent signed

Exclusion Criteria:

• Other progressive disease (cancer uncontrolled for less than 2 years)

• Rectal Cancer (located less than 15 cm from the anal verge endoscopy or sub-peritoneal)

• ANC <2000 / mm3 for group 1 and ANC <1500 / mm3 for group 2 and platelets <100,000 / mm3 or hemoglobin <9 g / dL

• Neuropathy for patients in group 1

• Known deficit of dihydropyrimidine dehydrogenase (DPD)

• Patients with severe hepatic insufficiency

• Any contrindication to the drugs used in the study

• Inability to submit to medical follow-up for geographical, social or psychological reasons.

Related Conditions & MeSH terms

• Adenocarcinoma
• Colonic Adenocarcinoma

Intervention

Drug:
• LV5FU2 or capectitabine

• FOLFOX4 or XELOX

Other:
• Observation

Drug:
• LV5FU2 or capecitabine

Locations

Country	Name	City	State
France	CH d'Abbeville	Abbeville CEDEX
France	CROMG	Agen
France	Centre hospitalier du Pays d'Aix	Aix-en-Provence
France	Centre hospitalier d'Albi	Albi
France	Clinique Claude Bernard	Albi
France	Clinique Claude Bernard	Albi
France	Centre Oncogard	Alès
France	Hôpital Sud	Amiens CEDEX 1
France	ICO Site Paul Papin	Angers CEDEX 2
France	CHU d'Angers	Angers CEDEX 9
France	HOP Privé	Annemasse
France	CH Victor Dupouy	Argenteuil
France	Hôpital Privé Bonnettes	Arras
France	Hôpital Les Bonnettes	Arras CEDEX
France	Centre Hospitalier Ardèche Méridionale	Aubenas CEDEX
France	CH D'Auxerre	Auxerre
France	Hôpital Henri Duffaut	Avignon
France	Institut Sainte Catherine	Avignon CEDEX
France	Hôpital de Bayeux	Bayeux CEDEX
France	Centre d'Oncologie et de Radiothérapie du Pays-Basque	Bayonne
France	CH Côte Basque	Bayonne CEDEX
France	CH de Beauvais	Beauvais
France	CH de Béziers	Béziers
France	CH de Blois	Blois
France	CHU Avicenne	BOBIGNY cedex
France	Polyclinique Bordeaux Nord	Bordeaux CEDEX
France	Hôpital Duchenne	Boulogne-sur-Mer
France	Hôpital Pierre Oudot	Bourgoin-Jallieu
France	Clinique Pasteur Saint Esprit	Brest
France	CHU Côte de Nacre	Caen
France	CH	Cahors
France	Infirmerie Protestante de Lyon	Caluire-et-Cuire
France	CH William Morey	Chalon-sur-Saône
France	Hôpital Privé Sainte Marie	Chalon-sur-Saône
France	Centre Hospitalier Général	Châlons-en-Champagne
France	Centre Hospitalier Métropole Savoie	Chambery CEDEX
France	Centre Hospitalier Public du Cotentin	Cherbourg
France	CH	Cherbourg
France	CHU Estaing	Clermont-Ferrand
France	Hopitaux Civils de Colmar	Colmar
France	Centre Hospitalier	Compiègne CEDEX
France	CH	Contamine sur Arve
France	Centre Hospitalier Sud Francilien	Corbeil-Essonnes
France	Clinique des Cèdres	Cornebarrieu
France	Clinique des Cèdres	Cornebarrieu
France	Centre Hospitalier de Dax	Dax CEDEX
France	Service de médecine	Digne-les-Bains
France	Centre Goerges François Leclerc	Dijon
France	Institut de Cancérologie de Bourgogne - GRRECC	Dijon
France	Hôpital François Mitterand	Dijon CEDEX
France	CHI Elbeuf-Louviers-Val de Reuil	Elbeuf
France	Centre médical des Forcilles	Férolles-Attilly
France	CH	Flers
France	CHU de Fort de France	Fort De France	Guadeloupe
France	CHI de Fréjus Saint-Raphaël	Fréjus
France	Centre Hospitalier	Gap
France	Centre Hospitalier	Gonesse
France	CH	Gonesse
France	CHU de Grenoble - Hôpital A. Michallon	Grenoble CEDEX
France	CH Marne La Vallée-Jossigny	Jossigny
France	CHD Vendée	La Roche-sur-Yon
France	Groupe Hospitalier de la Rochelle Ré-Aunis	La Rochelle
France	CH	Le Coudray
France	CH du Mans	Le Mans CEDEX 9
France	Centre Oscar Lambret	Lille
France	CHRU Hôpital Claude Huriez 4eme EST	Lille
France	CHU Dupuytren	Limoges
France	Clinique François Chénieux	Limoges
France	CH	Longjumeau
France	CHBS - Hôpital du Scorff	Lorient CEDEX
France	CH ST Joseph-ST Luc	Lyon
France	CHU de Lyon - Croix Rousse	Lyon
France	Clinique Mutualiste Eugène André	Lyon
France	Hôpital Edouard Herriot	Lyon
France	Hôpital Privé Jean Mermoz	Lyon
France	Clinique de la Sauvegarde	Lyon CEDEX 09
France	Centre Radiologie	Macon
France	Hôpital Européen Marseille	Marseille CEDEX 03
France	Hopital Nord	Marseille CEDEX 20
France	CHU La Timone	Marseille CEDEX 5
France	CH de Meaux	Meaux
France	Hôpital Layne	Mont-de-Marsan
France	Centre Hospitalier	Montélimar
France	Hôpital Monod	Montivilliers
France	Centre Hospitalier	Morlaix CEDEX
France	Centre Azuréen de Cancérologie	Mougins
France	Hôpital Privé du Confluent SAS	Nantes
France	Hôpital Américain de Paris	Neuilly-sur-Seine
France	Hôpital Pierre Bérégovoy	Nevers CEDEX
France	Centre Antoine Lacassagne	Nice CEDEX 2
France	CHU Carémeau	Nîmes
France	Centre Oncogard	Nîmes CEDEX 9
France	Hôpital de la Source	Orléans CEDEX 2
France	HEGP	Paris
France	Hôpital Cochin	Paris
France	Hôpital Privé des Peupliers	Paris
France	Hôpital Saint Antoine	Paris
France	Hôpital Saint Louis	Paris
France	Institut Montsouris	Paris
France	Pitié Salpêtière	Paris
France	Centre Hospitalier	Pau CEDEX
France	Polyclinique Francheville	Périgueux
France	Hôpital Haut Leveque	Pessac CEDEX
France	CHU Lyon Sud	Pierre-Bénite
France	Centre CARIO - HCPA	Plérin
France	Hôpital de la Milétrie	Poitiers
France	CH Annecy Genevois	Pringy
France	CHU Robert Debré	Reims CEDEX
France	Centre Eugène Marquis	Rennes CEDEX
France	CHU de Pontchaillou	Rennes CEDEX 9
France	CH	Rodez
France	Hôpital Drome Nord	Romans-sur-Isère
France	Clinique Mathilde	Rouen CEDEX
France	CHU Charles Nicolle	Rouen CEDEX 01
France	Hôpital Privé Saint Grégoire	Saint Gregoire
France	ICO - Site René Gauducheau	Saint Herblain
France	Institut de Cancérologie Lucien Neuwirth	Saint Priest en Jarez
France	CH	Saint Quentin
France	Institut Curie	Saint-Cloud
France	Polyclinique Côte Basque Sud	Saint-Jean-de-Luz
France	Centre Hospitalier de Saint-Malo	Saint-Malo
France	Hôpital d'Instruction des Armées Begin	Saint-Mandé
France	Polyclinique Saint Claude	Saint-Quentin
France	CH Saintonge	Saintes
France	CH Morlevat	Semur-en-Auxois
France	CH	Senlis CEDEX
France	Centre Hospitalier	Sens CEDEX
France	CH Région Saint Omer	St Omer
France	Centre Paul Strauss	Strasbourg
France	Clinique Sainte Anne	Strasbourg
France	Hôpitaux du Leman	Thonon-les-Bains
France	Hôpital Sainte Musse	Toulon
France	Hôpital Sainte Musse	Toulon
France	Clinique Saint Jean du Languedoc	Toulouse
France	Hôpitaux Trousseau	Tours CEDEX 9
France	Centre Hospitalier	Valenciennes
France	CHU de Nancy-Bradois	Vandoeuvre les nancy
France	Institut de Cancérologie de Lorraine	Vandoeuvre les nancy
France	Paul Brousse	Villejuif
France	Centre Hospitalier	Villeneuve-Saint-Georges

Sponsors (1)

Lead Sponsor	Collaborator
Federation Francophone de Cancerologie Digestive

Country where clinical trial is conducted

France, 

References & Publications (1)

Aparicio T, Francois E, Cristol-Dalstein L, Carola E, Maillard E, Paillaud E, Retornaz F, Faroux R, Andre T, Bedenne L, Seitz JF. PRODIGE 34-FFCD 1402-ADAGE: Adjuvant chemotherapy in elderly patients with resected stage III colon cancer: A randomized phase 3 trial. Dig Liver Dis. 2016 Feb;48(2):206-7. doi: 10.1016/j.dld.2015.11.023. Epub 2015 Dec 2. No abstract available. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The 3-year disease-free survival		3 years after last patient in
Secondary	Overal survival		5 years after last patient in
Secondary	Observed toxicities, graded according to NCI-CTC v4		3 years after last patient in