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

Sponsor

Federation Francophone de Cancerologie Digestive (Other)

Overall Status

Recruiting

CT.gov ID

NCT02355379

Collaborator

(none)

774

Enrollment

140

Locations

Arms

127

Duration (Months)

5.5

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Colonic Adenocarcinoma	Drug: LV5FU2 or capectitabine Drug: FOLFOX4 or XELOX Other: Observation Drug: LV5FU2 or capecitabine	Phase 3

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

774 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Jan 1, 2015

Anticipated Primary Completion Date :

Aug 1, 2023

Anticipated Study Completion Date :

Aug 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: GROUP1 -ARM A LV5FU2 or capecitabine	Drug: LV5FU2 or capectitabine
Experimental: GROUP1-ARMB FOLFOX4 or XELOX	Drug: FOLFOX4 or XELOX
Experimental: GROUP2- ARM C Observation	Other: Observation
Experimental: GROUP2-ARM D LV5FU2 or capecitabine	Drug: LV5FU2 or capecitabine

Outcome Measures

Primary Outcome Measures

The 3-year disease-free survival [3 years after last patient in]

Secondary Outcome Measures

Overal survival [5 years after last patient in]
Observed toxicities, graded according to NCI-CTC v4 [3 years after last patient in]

Eligibility Criteria

Criteria

Ages Eligible for Study:

75 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	CHU de Fort de France	Fort De France	Guadeloupe	France	97261
2	CH d'Abbeville	Abbeville CEDEX		France	80142
3	CROMG	Agen		France
4	Centre hospitalier du Pays d'Aix	Aix-en-Provence		France	13616
5	Centre hospitalier d'Albi	Albi		France	81000
6	Clinique Claude Bernard	Albi		France	81030
7	Clinique Claude Bernard	Albi		France
8	Centre Oncogard	Alès		France	30103
9	Hôpital Sud	Amiens CEDEX 1		France	80054
10	ICO Site Paul Papin	Angers CEDEX 2		France	49055
11	CHU d'Angers	Angers CEDEX 9		France	49933
12	HOP Privé	Annemasse		France
13	CH Victor Dupouy	Argenteuil		France	95107
14	Hôpital Les Bonnettes	Arras CEDEX		France	62012
15	Hôpital Privé Bonnettes	Arras		France
16	Centre Hospitalier Ardèche Méridionale	Aubenas CEDEX		France	07205
17	CH D'Auxerre	Auxerre		France	89000
18	Institut Sainte Catherine	Avignon CEDEX		France	84918
19	Hôpital Henri Duffaut	Avignon		France	84902
20	Hôpital de Bayeux	Bayeux CEDEX		France	14401
21	CH Côte Basque	Bayonne CEDEX		France	64109
22	Centre d'Oncologie et de Radiothérapie du Pays-Basque	Bayonne		France	64100
23	CH de Beauvais	Beauvais		France	60021
24	CH de Blois	Blois		France	41000
25	CHU Avicenne	BOBIGNY cedex		France	93009
26	Polyclinique Bordeaux Nord	Bordeaux CEDEX		France	33077
27	Hôpital Duchenne	Boulogne-sur-Mer		France	62321
28	Hôpital Pierre Oudot	Bourgoin-Jallieu		France	38300
29	Clinique Pasteur Saint Esprit	Brest		France	29200
30	CH de Béziers	Béziers		France	34525
31	CHU Côte de Nacre	Caen		France	14033
32	CH	Cahors		France
33	Infirmerie Protestante de Lyon	Caluire-et-Cuire		France	69300
34	CH William Morey	Chalon-sur-Saône		France	71100
35	Hôpital Privé Sainte Marie	Chalon-sur-Saône		France	71100
36	Centre Hospitalier Métropole Savoie	Chambery CEDEX		France	73011
37	Centre Hospitalier Public du Cotentin	Cherbourg		France	50102
38	CH	Cherbourg		France
39	Centre Hospitalier Général	Châlons-en-Champagne		France	51005
40	CHU Estaing	Clermont-Ferrand		France	63003
41	Hopitaux Civils de Colmar	Colmar		France	68024
42	Centre Hospitalier	Compiègne CEDEX		France	60321
43	CH	Contamine sur Arve		France
44	Centre Hospitalier Sud Francilien	Corbeil-Essonnes		France	91106
45	Clinique des Cèdres	Cornebarrieu		France	31700
46	Clinique des Cèdres	Cornebarrieu		France
47	Centre Hospitalier de Dax	Dax CEDEX		France	40107
48	Service de médecine	Digne-les-Bains		France	04000
49	Hôpital François Mitterand	Dijon CEDEX		France	21079
50	Institut de Cancérologie de Bourgogne - GRRECC	Dijon		France	21000
51	Centre Goerges François Leclerc	Dijon		France	21079
52	CHI Elbeuf-Louviers-Val de Reuil	Elbeuf		France	76503
53	CH	Flers		France
54	CHI de Fréjus Saint-Raphaël	Fréjus		France	83600
55	Centre médical des Forcilles	Férolles-Attilly		France	77150
56	Centre Hospitalier	Gap		France	05007
57	Centre Hospitalier	Gonesse		France	95500
58	CH	Gonesse		France
59	CHU de Grenoble - Hôpital A. Michallon	Grenoble CEDEX		France	38043
60	CH Marne La Vallée-Jossigny	Jossigny		France	77600
61	CHD Vendée	La Roche-sur-Yon		France	85925
62	Groupe Hospitalier de la Rochelle Ré-Aunis	La Rochelle		France	17019
63	CH	Le Coudray		France
64	CH du Mans	Le Mans CEDEX 9		France	72037
65	Centre Oscar Lambret	Lille		France	59037
66	CHRU Hôpital Claude Huriez 4eme EST	Lille		France	59037
67	Clinique François Chénieux	Limoges		France	87000
68	CHU Dupuytren	Limoges		France	87042
69	CH	Longjumeau		France	91164
70	CHBS - Hôpital du Scorff	Lorient CEDEX		France	56322
71	Clinique de la Sauvegarde	Lyon CEDEX 09		France	69009
72	Clinique Mutualiste Eugène André	Lyon		France	69003
73	Hôpital Privé Jean Mermoz	Lyon		France	69008
74	CHU de Lyon - Croix Rousse	Lyon		France	69317
75	CH ST Joseph-ST Luc	Lyon		France	69365
76	Hôpital Edouard Herriot	Lyon		France	69437
77	Centre Radiologie	Macon		France
78	Hôpital Européen Marseille	Marseille CEDEX 03		France	13331
79	Hopital Nord	Marseille CEDEX 20		France	13915
80	CHU La Timone	Marseille CEDEX 5		France	13385
81	CH de Meaux	Meaux		France	77100
82	Hôpital Layne	Mont-de-Marsan		France	40024
83	Hôpital Monod	Montivilliers		France	76290
84	Centre Hospitalier	Montélimar		France	26216
85	Centre Hospitalier	Morlaix CEDEX		France	29672
86	Centre Azuréen de Cancérologie	Mougins		France	06250
87	Hôpital Privé du Confluent SAS	Nantes		France	44277
88	Hôpital Américain de Paris	Neuilly-sur-Seine		France	92200
89	Hôpital Pierre Bérégovoy	Nevers CEDEX		France	58033
90	Centre Antoine Lacassagne	Nice CEDEX 2		France	06189
91	Centre Oncogard	Nîmes CEDEX 9		France	30029
92	CHU Carémeau	Nîmes		France	30029
93	Hôpital de la Source	Orléans CEDEX 2		France	45067
94	Hôpital Privé des Peupliers	Paris		France	75013
95	Hôpital Saint Antoine	Paris		France	75571
96	HEGP	Paris		France
97	Hôpital Cochin	Paris		France
98	Hôpital Saint Louis	Paris		France
99	Institut Montsouris	Paris		France
100	Pitié Salpêtière	Paris		France
101	Centre Hospitalier	Pau CEDEX		France	64046
102	Hôpital Haut Leveque	Pessac CEDEX		France	33604
103	CHU Lyon Sud	Pierre-Bénite		France	64495
104	Centre CARIO - HCPA	Plérin		France	22190
105	Hôpital de la Milétrie	Poitiers		France	86021
106	CH Annecy Genevois	Pringy		France	74374
107	Polyclinique Francheville	Périgueux		France	24004
108	CHU Robert Debré	Reims CEDEX		France	51092
109	CHU de Pontchaillou	Rennes CEDEX 9		France	35033
110	Centre Eugène Marquis	Rennes CEDEX		France	35042
111	CH	Rodez		France
112	Hôpital Drome Nord	Romans-sur-Isère		France	26100
113	CHU Charles Nicolle	Rouen CEDEX 01		France	76031
114	Clinique Mathilde	Rouen CEDEX		France	76175
115	Hôpital Privé Saint Grégoire	Saint Gregoire		France	35768
116	ICO - Site René Gauducheau	Saint Herblain		France	44805
117	Institut de Cancérologie Lucien Neuwirth	Saint Priest en Jarez		France	42271
118	CH	Saint Quentin		France
119	Institut Curie	Saint-Cloud		France	92210
120	Polyclinique Côte Basque Sud	Saint-Jean-de-Luz		France	64500
121	Centre Hospitalier de Saint-Malo	Saint-Malo		France	35403
122	Hôpital d'Instruction des Armées Begin	Saint-Mandé		France	94163
123	Polyclinique Saint Claude	Saint-Quentin		France	02100
124	CH Saintonge	Saintes		France	17108
125	CH Morlevat	Semur-en-Auxois		France	21140
126	CH	Senlis CEDEX		France	60309
127	Centre Hospitalier	Sens CEDEX		France	89108
128	CH Région Saint Omer	St Omer		France	62505
129	Clinique Sainte Anne	Strasbourg		France	67000
130	Centre Paul Strauss	Strasbourg		France	67065
131	Hôpitaux du Leman	Thonon-les-Bains		France	74203
132	Hôpital Sainte Musse	Toulon		France	83000
133	Hôpital Sainte Musse	Toulon		France	83000
134	Clinique Saint Jean du Languedoc	Toulouse		France	31077
135	Hôpitaux Trousseau	Tours CEDEX 9		France	37044
136	Centre Hospitalier	Valenciennes		France	59322
137	CHU de Nancy-Bradois	Vandoeuvre les nancy		France	54511
138	Institut de Cancérologie de Lorraine	Vandoeuvre les nancy		France	54519
139	Paul Brousse	Villejuif		France
140	Centre Hospitalier	Villeneuve-Saint-Georges		France	94195