MedPath

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

Phase 3
Recruiting
Conditions
Colonic Adenocarcinoma
Interventions
Drug: LV5FU2 or capectitabine
Drug: FOLFOX4 or XELOX
Other: Observation
Registration Number
NCT02355379
Lead Sponsor
Federation Francophone de Cancerologie Digestive
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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
774
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
GROUP2-ARM DLV5FU2 or capecitabineLV5FU2 or capecitabine
GROUP1 -ARM ALV5FU2 or capectitabineLV5FU2 or capecitabine
GROUP1-ARMBFOLFOX4 or XELOXFOLFOX4 or XELOX
GROUP2- ARM CObservationObservation
Primary Outcome Measures
NameTimeMethod
The 3-year disease-free survival3 years after last patient in
Secondary Outcome Measures
NameTimeMethod
Overal survival5 years after last patient in
Observed toxicities, graded according to NCI-CTC v43 years after last patient in

Trial Locations

Locations (119)

Hopital Nord

🇫🇷

Marseille CEDEX 20, France

CH d'Abbeville

🇫🇷

Abbeville CEDEX, France

Centre hospitalier d'Albi

🇫🇷

Albi, France

CROMG

🇫🇷

Agen, France

Clinique Claude Bernard

🇫🇷

Albi, France

Centre Oncogard

🇫🇷

Nîmes CEDEX 9, France

Hôpital Sud

🇫🇷

Amiens CEDEX 1, France

CH Victor Dupouy

🇫🇷

Argenteuil, France

HOP Privé

🇫🇷

Annemasse, France

Hôpital Les Bonnettes

🇫🇷

Arras CEDEX, France

Hôpital Privé Bonnettes

🇫🇷

Arras, France

Centre Hospitalier Ardèche Méridionale

🇫🇷

Aubenas CEDEX, France

CH D'Auxerre

🇫🇷

Auxerre, France

CH Côte Basque

🇫🇷

Bayonne CEDEX, France

Hôpital de Bayeux

🇫🇷

Bayeux CEDEX, France

Centre d'Oncologie et de Radiothérapie du Pays-Basque

🇫🇷

Bayonne, France

CH de Beauvais

🇫🇷

Beauvais, 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

🇫🇷

Senlis CEDEX, France

Hôpital Privé Sainte Marie

🇫🇷

Chalon-sur-Saône, France

Centre Hospitalier Public du Cotentin

🇫🇷

Cherbourg, France

Centre Hospitalier Métropole Savoie

🇫🇷

Chambery CEDEX, France

CHU Estaing

🇫🇷

Clermont-Ferrand, France

Centre Hospitalier Sud Francilien

🇫🇷

Corbeil-Essonnes, France

Centre Hospitalier

🇫🇷

Villeneuve-Saint-Georges, France

Service de médecine

🇫🇷

Digne-les-Bains, France

Hôpital François Mitterand

🇫🇷

Dijon CEDEX, France

Institut de Cancérologie de Bourgogne - GRRECC

🇫🇷

Dijon, France

Centre Goerges François Leclerc

🇫🇷

Dijon, France

CHI Elbeuf-Louviers-Val de Reuil

🇫🇷

Elbeuf, France

CH Marne La Vallée-Jossigny

🇫🇷

Jossigny, France

CHI de Fréjus Saint-Raphaël

🇫🇷

Fréjus, France

CH du Mans

🇫🇷

Le Mans CEDEX 9, France

Groupe Hospitalier de la Rochelle Ré-Aunis

🇫🇷

La Rochelle, France

CHU Dupuytren

🇫🇷

Limoges, France

Clinique François Chénieux

🇫🇷

Limoges, France

CHRU Hôpital Claude Huriez 4eme EST

🇫🇷

Lille, France

Clinique de la Sauvegarde

🇫🇷

Lyon CEDEX 09, France

Clinique Mutualiste Eugène André

🇫🇷

Lyon, France

Hôpital Privé Jean Mermoz

🇫🇷

Lyon, France

CH ST Joseph-ST Luc

🇫🇷

Lyon, France

Centre Radiologie

🇫🇷

Macon, France

CHU La Timone

🇫🇷

Marseille CEDEX 5, France

Hôpital Monod

🇫🇷

Montivilliers, France

CHU Carémeau

🇫🇷

Nîmes, France

HEGP

🇫🇷

Paris, France

Hôpital Cochin

🇫🇷

Paris, France

Hôpital Saint Louis

🇫🇷

Paris, France

Pitié Salpêtière

🇫🇷

Paris, France

Hôpital Haut Leveque

🇫🇷

Pessac CEDEX, France

Centre CARIO - HCPA

🇫🇷

Plérin, France

Hôpital de la Milétrie

🇫🇷

Poitiers, France

CH Annecy Genevois

🇫🇷

Pringy, France

Polyclinique Francheville

🇫🇷

Périgueux, France

CHU Robert Debré

🇫🇷

Reims CEDEX, France

CHU Charles Nicolle

🇫🇷

Rouen CEDEX 01, France

CHU de Pontchaillou

🇫🇷

Rennes CEDEX 9, France

Hôpital Drome Nord

🇫🇷

Romans-sur-Isère, France

Centre Eugène Marquis

🇫🇷

Rennes CEDEX, France

ICO - Site René Gauducheau

🇫🇷

Saint Herblain, France

Institut de Cancérologie Lucien Neuwirth

🇫🇷

Saint Priest en Jarez, France

Hôpital Privé Saint Grégoire

🇫🇷

Saint Gregoire, France

Centre Hospitalier de Saint-Malo

🇫🇷

Saint-Malo, France

Polyclinique Saint Claude

🇫🇷

Saint-Quentin, France

CH Région Saint Omer

🇫🇷

St Omer, France

CH Morlevat

🇫🇷

Semur-en-Auxois, France

Hôpital d'Instruction des Armées Begin

🇫🇷

Saint-Mandé, France

Clinique Sainte Anne

🇫🇷

Strasbourg, France

Hôpitaux du Leman

🇫🇷

Thonon-les-Bains, France

Centre Paul Strauss

🇫🇷

Strasbourg, France

Hôpital Sainte Musse

🇫🇷

Toulon, France

CHU de Nancy-Bradois

🇫🇷

Vandoeuvre les nancy, France

Clinique Saint Jean du Languedoc

🇫🇷

Toulouse, France

Hôpitaux Trousseau

🇫🇷

Tours CEDEX 9, France

Paul Brousse

🇫🇷

Villejuif, France

Institut de Cancérologie de Lorraine

🇫🇷

Vandoeuvre les nancy, France

ICO Site Paul Papin

🇫🇷

Angers CEDEX 2, France

CHU d'Angers

🇫🇷

Angers CEDEX 9, France

Institut Sainte Catherine

🇫🇷

Avignon CEDEX, France

CH William Morey

🇫🇷

Chalon-sur-Saône, France

Infirmerie Protestante de Lyon

🇫🇷

Caluire-et-Cuire, France

Centre Hospitalier Général

🇫🇷

Châlons-en-Champagne, France

Clinique des Cèdres

🇫🇷

Cornebarrieu, France

Centre Hospitalier de Dax

🇫🇷

Dax CEDEX, France

Centre médical des Forcilles

🇫🇷

Férolles-Attilly, France

CHD Vendée

🇫🇷

La Roche-sur-Yon, France

Centre Oscar Lambret

🇫🇷

Lille, France

CHBS - Hôpital du Scorff

🇫🇷

Lorient CEDEX, France

CHU de Lyon - Croix Rousse

🇫🇷

Lyon, France

Hôpital Européen Marseille

🇫🇷

Marseille CEDEX 03, France

Hôpital Edouard Herriot

🇫🇷

Lyon, France

CH de Meaux

🇫🇷

Meaux, France

Hôpital Privé du Confluent SAS

🇫🇷

Nantes, France

Hôpital Pierre Bérégovoy

🇫🇷

Nevers CEDEX, France

Centre Antoine Lacassagne

🇫🇷

Nice CEDEX 2, France

Hôpital Saint Antoine

🇫🇷

Paris, France

Hôpital de la Source

🇫🇷

Orléans CEDEX 2, France

Hôpital Privé des Peupliers

🇫🇷

Paris, France

Institut Montsouris

🇫🇷

Paris, France

CHU Lyon Sud

🇫🇷

Pierre-Bénite, France

Institut Curie

🇫🇷

Saint-Cloud, France

Clinique Mathilde

🇫🇷

Rouen CEDEX, France

CH Saintonge

🇫🇷

Saintes, France

Centre Azuréen de Cancérologie

🇫🇷

Mougins, France

Centre hospitalier du Pays d'Aix

🇫🇷

Aix-en-Provence, France

CH de Béziers

🇫🇷

Béziers, France

CHU de Grenoble - Hôpital A. Michallon

🇫🇷

Grenoble CEDEX, France

Hôpital Henri Duffaut

🇫🇷

Avignon, France

Hopitaux Civils de Colmar

🇫🇷

Colmar, France

Hôpital Layne

🇫🇷

Mont-de-Marsan, France

Hôpital Américain de Paris

🇫🇷

Neuilly-sur-Seine, France

Polyclinique Côte Basque Sud

🇫🇷

Saint-Jean-de-Luz, France

CHU de Fort de France

🇫🇷

Fort De France, Guadeloupe, France

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