Clinical trial NCT02355379: Randomised Study Evaluating Adjuvant Chemotherapy After Resection of Stage III Colonic Adenocarcinoma in Patients of 70 and Over
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Colonic Adenocarcinoma
Keywords: Adjuvant chemotherapy in colonic adenocarcinoma in elderly
Lead sponsor: Federation Francophone de Cancerologie Digestive
Sponsor class: OTHER
First posted: 2015-02-04
Enrollment: 774
Sex: ALL
Minimum age (years): 75
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: The 3-year disease-free survival
timeFrame: 3 years after last patient in
Secondary outcomes:
measure: Overal survival
timeFrame: 5 years after last patient in
measure: Observed toxicities, graded according to NCI-CTC v4
timeFrame: 3 years after last patient in
Other outcomes:
Locations:
city: Fort De France
country: France
facility: CHU de Fort de France
state: Guadeloupe
city: Abbeville CEDEX
country: France
facility: CH d'Abbeville
city: Agen
country: France
facility: CROMG
city: Aix-en-Provence
country: France
facility: Centre hospitalier du Pays d'Aix
city: Albi
country: France
facility: Centre hospitalier d'Albi
city: Albi
country: France
facility: Clinique Claude Bernard
city: Albi
country: France
facility: Clinique Claude Bernard
city: Alès
country: France
facility: Centre Oncogard
city: Amiens CEDEX 1
country: France
facility: Hôpital Sud
city: Angers CEDEX 2
country: France
facility: ICO Site Paul Papin
city: Angers CEDEX 9
country: France
facility: CHU d'Angers
city: Annemasse
country: France
facility: HOP Privé
city: Argenteuil
country: France
facility: CH Victor Dupouy
city: Arras CEDEX
country: France
facility: Hôpital Les Bonnettes
city: Arras
country: France
facility: Hôpital Privé Bonnettes
city: Aubenas CEDEX
country: France
facility: Centre Hospitalier Ardèche Méridionale
city: Auxerre
country: France
facility: CH D'Auxerre
city: Avignon CEDEX
country: France
facility: Institut Sainte Catherine
city: Avignon
country: France
facility: Hôpital Henri Duffaut
city: Bayeux CEDEX
country: France
facility: Hôpital de Bayeux
city: Bayonne CEDEX
country: France
facility: CH Côte Basque
city: Bayonne
country: France
facility: Centre d'Oncologie et de Radiothérapie du Pays-Basque
city: Beauvais
country: France
facility: CH de Beauvais
city: Blois
country: France
facility: CH de Blois
city: BOBIGNY cedex
country: France
facility: CHU Avicenne
city: Bordeaux CEDEX
country: France
facility: Polyclinique Bordeaux Nord
city: Boulogne-sur-Mer
country: France
facility: Hôpital Duchenne
city: Bourgoin-Jallieu
country: France
facility: Hôpital Pierre Oudot
city: Brest
country: France
facility: Clinique Pasteur Saint Esprit
city: Béziers
country: France
facility: CH de Béziers
city: Caen
country: France
facility: CHU Côte de Nacre
city: Cahors
country: France
facility: CH
city: Caluire-et-Cuire
country: France
facility: Infirmerie Protestante de Lyon
city: Chalon-sur-Saône
country: France
facility: CH William Morey
city: Chalon-sur-Saône
country: France
facility: Hôpital Privé Sainte Marie
city: Chambery CEDEX
country: France
facility: Centre Hospitalier Métropole Savoie
city: Cherbourg
country: France
facility: Centre Hospitalier Public du Cotentin
city: Cherbourg
country: France
facility: CH
city: Châlons-en-Champagne
country: France
facility: Centre Hospitalier Général
city: Clermont-Ferrand
country: France
facility: CHU Estaing
city: Colmar
country: France
facility: Hopitaux Civils de Colmar
city: Compiègne CEDEX
country: France
facility: Centre Hospitalier
city: Contamine sur Arve
country: France
facility: CH
city: Corbeil-Essonnes
country: France
facility: Centre Hospitalier Sud Francilien
city: Cornebarrieu
country: France
facility: Clinique des Cèdres
city: Cornebarrieu
country: France
facility: Clinique des Cèdres
city: Dax CEDEX
country: France
facility: Centre Hospitalier de Dax
city: Digne-les-Bains
country: France
facility: Service de médecine
city: Dijon CEDEX
country: France
facility: Hôpital François Mitterand
city: Dijon
country: France
facility: Institut de Cancérologie de Bourgogne - GRRECC
city: Dijon
country: France
facility: Centre Goerges François Leclerc
city: Elbeuf
country: France
facility: CHI Elbeuf-Louviers-Val de Reuil
city: Flers
country: France
facility: CH
city: Fréjus
country: France
facility: CHI de Fréjus Saint-Raphaël
city: Férolles-Attilly
country: France
facility: Centre médical des Forcilles
city: Gap
country: France
facility: Centre Hospitalier
city: Gonesse
country: France
facility: Centre Hospitalier
city: Gonesse
country: France
facility: CH
city: Grenoble CEDEX
country: France
facility: CHU de Grenoble - Hôpital A. Michallon
city: Jossigny
country: France
facility: CH Marne La Vallée-Jossigny
city: La Roche-sur-Yon
country: France
facility: CHD Vendée
city: La Rochelle
country: France
facility: Groupe Hospitalier de la Rochelle Ré-Aunis
city: Le Coudray
country: France
facility: CH
city: Le Mans CEDEX 9
country: France
facility: CH du Mans
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lille
country: France
facility: CHRU Hôpital Claude Huriez 4eme EST
city: Limoges
country: France
facility: Clinique François Chénieux
city: Limoges
country: France
facility: CHU Dupuytren
city: Longjumeau
country: France
facility: CH
city: Lorient CEDEX
country: France
facility: CHBS - Hôpital du Scorff
city: Lyon CEDEX 09
country: France
facility: Clinique de la Sauvegarde
city: Lyon
country: France
facility: Clinique Mutualiste Eugène André
city: Lyon
country: France
facility: Hôpital Privé Jean Mermoz
city: Lyon
country: France
facility: CHU de Lyon - Croix Rousse
city: Lyon
country: France
facility: CH ST Joseph-ST Luc
city: Lyon
country: France
facility: Hôpital Edouard Herriot
city: Macon
country: France
facility: Centre Radiologie
city: Marseille CEDEX 03
country: France
facility: Hôpital Européen Marseille
city: Marseille CEDEX 20
country: France
facility: Hopital Nord
city: Marseille CEDEX 5
country: France
facility: CHU La Timone
city: Meaux
country: France
facility: CH de Meaux
city: Mont-de-Marsan
country: France
facility: Hôpital Layne
city: Montivilliers
country: France
facility: Hôpital Monod
city: Montélimar
country: France
facility: Centre Hospitalier
city: Morlaix CEDEX
country: France
facility: Centre Hospitalier
city: Mougins
country: France
facility: Centre Azuréen de Cancérologie
city: Nantes
country: France
facility: Hôpital Privé du Confluent SAS
city: Neuilly-sur-Seine
country: France
facility: Hôpital Américain de Paris
city: Nevers CEDEX
country: France
facility: Hôpital Pierre Bérégovoy
city: Nice CEDEX 2
country: France
facility: Centre Antoine Lacassagne
city: Nîmes CEDEX 9
country: France
facility: Centre Oncogard
city: Nîmes
country: France
facility: CHU Carémeau
city: Orléans CEDEX 2
country: France
facility: Hôpital de la Source
city: Paris
country: France
facility: Hôpital Privé des Peupliers
city: Paris
country: France
facility: Hôpital Saint Antoine
city: Paris
country: France
facility: HEGP
city: Paris
country: France
facility: Hôpital Cochin
city: Paris
country: France
facility: Hôpital Saint Louis
city: Paris
country: France
facility: Institut Montsouris
city: Paris
country: France
facility: Pitié Salpêtière
city: Pau CEDEX
country: France
facility: Centre Hospitalier
city: Pessac CEDEX
country: France
facility: Hôpital Haut Leveque
city: Pierre-Bénite
country: France
facility: CHU Lyon Sud
city: Plérin
country: France
facility: Centre CARIO - HCPA
city: Poitiers
country: France
facility: Hôpital de la Milétrie
city: Pringy
country: France
facility: CH Annecy Genevois
city: Périgueux
country: France
facility: Polyclinique Francheville
city: Reims CEDEX
country: France
facility: CHU Robert Debré
city: Rennes CEDEX 9
country: France
facility: CHU de Pontchaillou
city: Rennes CEDEX
country: France
facility: Centre Eugène Marquis
city: Rodez
country: France
facility: CH
city: Romans-sur-Isère
country: France
facility: Hôpital Drome Nord
city: Rouen CEDEX 01
country: France
facility: CHU Charles Nicolle
city: Rouen CEDEX
country: France
facility: Clinique Mathilde
city: Saint Gregoire
country: France
facility: Hôpital Privé Saint Grégoire
city: Saint Herblain
country: France
facility: ICO - Site René Gauducheau
city: Saint Priest en Jarez
country: France
facility: Institut de Cancérologie Lucien Neuwirth
city: Saint Quentin
country: France
facility: CH
city: Saint-Cloud
country: France
facility: Institut Curie
city: Saint-Jean-de-Luz
country: France
facility: Polyclinique Côte Basque Sud
city: Saint-Malo
country: France
facility: Centre Hospitalier de Saint-Malo
city: Saint-Mandé
country: France
facility: Hôpital d'Instruction des Armées Begin
city: Saint-Quentin
country: France
facility: Polyclinique Saint Claude
city: Saintes
country: France
facility: CH Saintonge
city: Semur-en-Auxois
country: France
facility: CH Morlevat
city: Senlis CEDEX
country: France
facility: CH
city: Sens CEDEX
country: France
facility: Centre Hospitalier
city: St Omer
country: France
facility: CH Région Saint Omer
city: Strasbourg
country: France
facility: Clinique Sainte Anne
city: Strasbourg
country: France
facility: Centre Paul Strauss
city: Thonon-les-Bains
country: France
facility: Hôpitaux du Leman
city: Toulon
country: France
facility: Hôpital Sainte Musse
city: Toulon
country: France
facility: Hôpital Sainte Musse
city: Toulouse
country: France
facility: Clinique Saint Jean du Languedoc
city: Tours CEDEX 9
country: France
facility: Hôpitaux Trousseau
city: Valenciennes
country: France
facility: Centre Hospitalier
city: Vandoeuvre les nancy
country: France
facility: CHU de Nancy-Bradois
city: Vandoeuvre les nancy
country: France
facility: Institut de Cancérologie de Lorraine
city: Villejuif
country: France
facility: Paul Brousse
city: Villeneuve-Saint-Georges
country: France
facility: Centre Hospitalier
Study officials:
affiliation: FFCD member
name: Thomas Aparicio, Pr
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.