ITACA-S: Intergroup Trial of Adjuvant Chemotherapy in Adenocarcinoma of the Stomach

Sponsor

Mario Negri Institute for Pharmacological Research (Other)

Overall Status

Completed

CT.gov ID

NCT01640782

Collaborator

Aventis Pharmaceuticals (Industry), Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente (Other), Gruppo Oncologico Italiano di Ricerca Clinica (Other), Gruppo Oncologico del Nord-Ovest (Other), Italian Trial in Medical Oncology (Other), Southern Italy Cooperative Oncology Group (Other), Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori (Other), Oncotech (Industry)

1,100

Enrollment

101

Locations

Arms

Duration (Months)

10.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Open label, randomised, multicenter, superiority study for efficacy. Patients with histologically proven adenocarcinoma of the stomach or gastroesophageal junction without gross or microscopic evidence of residual disease after surgery with curative intent and fulfilling all the inclusion/exclusion criteria are eligible for this study.

Condition or Disease	Intervention/Treatment	Phase
Adenocarcinoma of the Stomach Adenocarcinoma of the Gastroesophageal Junction	Drug: Irinotecan, Leucovorin, 5-Fluorouracil, Docetaxel, Cisplatin Drug: Leucovorin, 5-Fluorouracil	Phase 3

Detailed Description

Allocation to treatment will be done centrally using a randomisation scheme and will be stratified by center and nodal involvement (N- vs. N+). Access to random system will be allowed by phone or via web.

All included patients in both groups will received fixed period of 18 weeks of treatment unless unacceptable toxicity or disease relapse during treatment. After cessation of therapy, patients will have a follow-up period while not receiving further treatment. After relapse further chemotherapy is left to the investigator's judgement. When the last patient is randomised, follow-up will be truncated at the achievement of the required number of events.

Time to progression and time to death are the main study outcomes. During the course of the trial, an independent Data and Safety Monitoring Board (DSMB) will advise the Steering Committee on efficacy and/or safety aspects of the study.

Study Design

Study Type:

Interventional

Actual Enrollment :

1100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Open Label, Randomised, Multicenter Phase III Study of Adjuvant Chemotherapy in Radically Resected Adenocarcinoma of the Stomach or Gastroesophageal Junction: Comparison of a Sequential Treatment (CPT-11+5-FU/LV --> TXT+CDDP) Versus a 5-FU/LV Regimen

Study Start Date :

Feb 1, 2005

Actual Primary Completion Date :

Jan 1, 2013

Actual Study Completion Date :

Jan 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sequential regimen Sequential treatment with CPT-11 plus Fluorouracil (FU), folinic acid (LV) and Docetaxel (TXT) plus Cisplatin (CDDP)	Drug: Irinotecan, Leucovorin, 5-Fluorouracil, Docetaxel, Cisplatin Irinotecan (CPT-11) 180 mg/m2, given as 60 min. i.v. infusion on day 1 every 2 weeks followed by Leucovorin (LV) 100 mg/m2, given as a 2h i.v. infusion on days 1 and 2 every 2 weeks followed by 5-Fluorouracil (5-FU) 400 mg/m2 given as bolus, and then 5-Fluorouracil (5-FU) 600 mg/m2 given as a 22h continuous infusion on days 1 and 2, every 2 weeks for 4 administrations. After 3 weeks from last infusion: Docetaxel (TXT) 75 mg/m2, given as a 1h i.v. infusion on day 1 followed by Cisplatin (CDDP) 75 mg/m2, given as a 1h i.v. infusion on.day 1, every 3 weeks, for 3 cycles.
Active Comparator: De Gramont regimen Fluorouracil (5-FU), folinic acid (LV)	Drug: Leucovorin, 5-Fluorouracil Leucovorin (LV) 100 mg/m2, given as a 2h i.v. infusion on days 1 and 2 every 2 weeks followed by 5-Fluorouracil (5-FU) 400 mg/m2 given as bolus, and then 5-Fluorouracil (5-FU) 600 mg/m2 given as a 22h continuous infusion on days 1 and 2, every 2 weeks for 9 administrations.

Arm

Intervention/Treatment

Experimental: Sequential regimen

Sequential treatment with CPT-11 plus Fluorouracil (FU), folinic acid (LV) and Docetaxel (TXT) plus Cisplatin (CDDP)

Drug: Irinotecan, Leucovorin, 5-Fluorouracil, Docetaxel, Cisplatin

Irinotecan (CPT-11) 180 mg/m2, given as 60 min. i.v. infusion on day 1 every 2 weeks followed by Leucovorin (LV) 100 mg/m2, given as a 2h i.v. infusion on days 1 and 2 every 2 weeks followed by 5-Fluorouracil (5-FU) 400 mg/m2 given as bolus, and then 5-Fluorouracil (5-FU) 600 mg/m2 given as a 22h continuous infusion on days 1 and 2, every 2 weeks for 4 administrations. After 3 weeks from last infusion: Docetaxel (TXT) 75 mg/m2, given as a 1h i.v. infusion on day 1 followed by Cisplatin (CDDP) 75 mg/m2, given as a 1h i.v. infusion on.day 1, every 3 weeks, for 3 cycles.

Active Comparator: De Gramont regimen

Fluorouracil (5-FU), folinic acid (LV)

Drug: Leucovorin, 5-Fluorouracil

Leucovorin (LV) 100 mg/m2, given as a 2h i.v. infusion on days 1 and 2 every 2 weeks followed by 5-Fluorouracil (5-FU) 400 mg/m2 given as bolus, and then 5-Fluorouracil (5-FU) 600 mg/m2 given as a 22h continuous infusion on days 1 and 2, every 2 weeks for 9 administrations.

Outcome Measures

Primary Outcome Measures

Progression Free Survival will be defined as the time from date of randomisation to date of first appearance of local, regional or distant relapse, or death from any cause; patients alive without relapse will be censored at date last known to be alive. [3 years]

Secondary Outcome Measures

OS will be defined as the time from date of randomisation to date of death by any cause, with living patients censored at date last known to be alive [3 years]
Toxicity, graded according to the NCI-CTG Expanded Common Toxicity Criteria [3 years]
Adverse events [3 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically proven adenocarcinoma of the stomach or gastroesophageal junction without gross or microscopic evidence of residual disease after surgery with curative intent;
Subtotal or total gastrectomy with at least D1 dissection;
Gastroesophageal junction adenocarcinoma extending to the stomach with the center lying 2 to 5 cm below the anatomic esophago-gastric junction;
Patients with nodal involvement (pN+) or patients without nodal involvement (pN0) with pT2b-3-4. It is recommended to examine at least 15 lymph nodes;
Age between 18 and 75 years;
ECOG performance status 0-1;
No previous chemotherapy and/or radiotherapy;
Complete staging procedures within 3 months prior to randomization;
Laboratory requirement (within 8 days prior to randomization):
Haematology (Neutrophils > 2.0 x 109 /L, Platelet > 100 x 109 /L, Hemoglobin > 10g/dL);
Hepatic function (Total bilirubin < 1 UNL, ASAT (SGOT) and ALAT (SGPT) < 2.5xUNL, Alkaline phosphatase < 2.5xUNL. Patients with ASAT or ALAT > 1.5xUNL associated with alkaline phosphatase > 2.5XUNL are not eligible.)
Renal function (Creatinine < 1.5 UNL. In presence of borderline values, the calculated creatinine clearance according to Cockroft-Gault formula, 60 ML/min.
Recovery from acute effects of surgery. The first infusion of study chemotherapy should be administered 3 to 8 weeks after surgery treatment;
Written informed consent signed and dated before randomization procedures, including expected cooperation of the patients for the treatment and follow-up, must be obtained and documented according to the local regulatory requirement.

Exclusion Criteria:

Non-radical surgery as assessed microscopically (no tumor-free margin of resection, positive biopsy of peritoneal suspicious lesions);
Synchronous metastases, even curatively resected;
Pregnant or lactating patients; patients with reproductive potential must implement adequate contraceptive measures;
Prior or concurrent history of:
positive HIV serology,
chronic diarrhoea,
chronic bowel inflammation or subobstruction,
neoplasm other than gastric cancer, except for: curatively treated non-melanoma skin cancer, in situ carcinoma of the cervix,
previous history of myocardial infarction within 1 year from study entry,
hypersensitivity reaction to polysorbate 80;
Presence of other systemic disease limiting drug administration and influencing patient survival:
uncontrolled hypertension,
high-risk uncontrolled arrhythmia,
unstable angina pectoris;
Symptomatic
peripheral neuropathy,
altered hearing > 2 grade by NCIC-CTG criteria;
Active uncontrolled infection.
Definite contra-indications for the use of corticosteroids: unstable diabetes mellitus, active peptic ulcer;
Concurrent administration of:
corticosteroids or equivalent except as use for the prophylactic medication regimen, treatment of acute hypersensitivity reactions or unless chronic treatment (initiated > 6 months prior to study entry) at low doses (< 20mg methylprednisolone or equivalent);
any other experimental drug under investigation: concurrent treatment with any other anticancer therapy, growth factors with preventive intent

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	ASL 6 - Fabriano	Fabriano	Ancona	Italy	60044
2	Ospedale Civile di Senigallia	Senigallia	Ancona	Italy	60019
3	dell'Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I	Torrette di Ancona	Ancona	Italy	60020
4	Presidio Ospedaliero di Ariano Irpino	Ariano Irpino	Avellino	Italy	83031
5	A.O. "Ospedale Treviglio-Caravaggio"	Treviglio	Bergamo	Italy	24047
6	P.O. di Monserrato - Policlinico Universitario di Cagliari	Monserrato	Cagliari	Italy	09042
7	P.O. di Monserrato	Monserrato	Cagliari	Italy	09042
8	Ospedale Civile "Ferrari"	Castrovillari	Cosenza	Italy	87012
9	Presidio Ospedaliero di Lamezia Terme	Lamezia Terme	Cosenza	Italy	88046
10	Ospedale "San Francesco" di Paola	Paola	Cosenza	Italy	87027
11	P.O. S. Lazzaro	Alba	Cuneo	Italy	12051
12	Ospedale Santa Maria Annunziata	Antella	Firenze	Italy	50011
13	Ospedale "San Giuseppe"	Empoli	Firenze	Italy	50053
14	Ospedale Civico di Carrara	Carrara	Massa Carrara	Italy	54033
15	A.O "San Gerardo" di Monza	Monza	Milano	Italy	20052
16	Istituto Clinico Humanitas	Rozzano	Milano	Italy	20089
17	Ospedale IRCCS Policlinico di San Donato	San Donato Milanese	Milano	Italy	20097
18	Presidio Ospedaliero "Serbelloni"di Gorgonzola	Vizzolo Predabissi	Milano	Italy	20070
19	Ospedale "B.Ramazzini"	Carpi	Modena	Italy	41012
20	Presidio Ospedaliero "Santa Maria delle Grazie"	Pozzuoli	Napoli	Italy	80087
21	Ospedale Civile di Este	Este	Padova	Italy	35043
22	Ospedale di Città di Castello - ASL 1 Umbria	Città di Castello	Perugia	Italy	06012
23	Ospedale di Marsciano - Servizio Oncologico	Marsciano	Perugia	Italy	06055
24	Ospedale "Santa Croce"	Fano	Pesaro	Italy	61032
25	Ospedale Civile "San Massimo"	Penne	Pesaro	Italy	65017
26	Centro di Riferimento Oncologico - INT	Aviano	Pordenone	Italy	33081
27	Centro di Riferimento Oncologico di Basilicata	Rionero in Vulture	Potenza	Italy	85028
28	P.O. di Faenza	Faenza	Ravenna	Italy	48018
29	P.O. Umberto I di Lugo	Lugo	Ravenna	Italy	48022
30	Ospedale Civile di Siderno	Siderno	Reggio Calabria	Italy	89048
31	Ospedale "San Luca"	Vallo della Lucania	Salerno	Italy	84078
32	Istituto per la Ricerca e la Cura del Cancro di Candiolo	Candiolo	Torino	Italy	10060
33	Ospedale Civile di Latisana	Latisana	Udine	Italy	33053
34	Azienda Ospedaliera S. Maria	Terni	Umbria	Italy	05100
35	Presidio Ospedaliero di Saronno - A.O. "Ospedale di Circolo di Busto Arsizio"	Saronno	Varallo	Italy	21047
36	A.O. "Ospedale di Circolo di Busto Arsizio"	Busto Arsizio	Varese	Italy	21052
37	Ospedale di Legnago	Legnago	Verona	Italy	37045
38	Ospedale di Montecchio Maggiore	Montecchio Maggiore	Vicenza	Italy	36075
39	Ospedale. S. Donato	Arezzo		Italy	52100
40	A.O. "G. Rummo"	Benevento		Italy	82100
41	Ospedali "Riuniti"	Bergamo		Italy	24128
42	Ospedale degli Infermi di Biella	Biella		Italy	13900
43	Ospedale Maggiore-Bellaria	Bologna		Italy	40133
44	A.O.Policlinico "S.Orsola-Malpighi"	Bologna		Italy	40138
45	Ospedale Sant'Orsola - Fatebenefratelli	Brescia		Italy	25122
46	Casa di Cura Poliambulanza di Brescia	Brescia		Italy	25124
47	Spedali Civili	Brescia		Italy	25125
48	P.O. Vittorio Emanuele	Catania		Italy	95100
49	Ospedale Garibaldi in Nesima	Catania		Italy	95123
50	A.O. Sant'Anna	Como		Italy	22100
51	Ospedale "Valduce"	Como		Italy	22100
52	A.O. "Ospedale Maggiore" di Crema	Crema		Italy	26013
53	Azienda Ospedaliera "Istituti Ospitalieri" di Cremona	Cremona		Italy	26100
54	A.O. "S.Croce e Carle"	Cuneo		Italy	12100
55	Azienda Ospedaliera Universitaria "S.Anna"	Ferrara		Italy	44100
56	A.O. Universitaria Careggi	Firenze		Italy	50134
57	A.O. "G.B.Morgagni-L.Pierantoni	Forli		Italy	47100
58	E.O. Ospedali Galliera di Genova	Genova		Italy	16128
59	Istituto Nazionale per la Ricerca sul Cancro	Genova		Italy	16132
60	P.O. "A.Manzoni" di Lecco	Lecco		Italy	23900
61	Azienda USL 6 - P.O. Livorno	Livorno		Italy	57100
62	Ospedale Civile di Casalpusterlengo	Lodi		Italy	26900
63	Ospedale "Campo di Marte"	Lucca		Italy	55100
64	A.O. "C.Poma"	Mantova		Italy	46100
65	Istituto Scientifico Universitario San Raffaele	Milano		Italy	20132
66	Istituto Nazionale per la cura dei tumori	Milano		Italy	20133
67	Istituto Europeo di Oncologia	Milano		Italy	20141
68	Azienda Ospedaliera "Ospedale San Carlo Borromeo"	Milano		Italy	20153
69	Azienda Ospedaliera "Luigi Sacco" Polo Universitario	Milano		Italy	20157
70	Azienda Ospedaliera "San Paolo" Polo Universitario	Milano		Italy
71	A.O. "D.Cotugno"	Napoli		Italy	80131
72	A.O.R.N. "Antonio Cardarelli"	Napoli		Italy	80131
73	Azienda Ospedaliera Universitaria "Federico II"	Napoli		Italy	80131
74	Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Pascale"	Napoli		Italy	80131
75	Azienda Ospedaliera "Maggiore della Carità"	Novara		Italy	28100
76	Azienda Ospedaliera di Padova	Padova		Italy	35128
77	Ospedali "Civico e Benfratelli - G. Di Cristina - Maurizio Ascoli"	Palermo		Italy	90127
78	Azienda Ospedaliera Universitaria Policlinico "Paolo Giaccone"di Palermo	Palermo		Italy	90129
79	Azienda Ospedaliera di Parma	Parma		Italy	43100
80	A.O."Ospedale S.Salvatore"	Pesaro		Italy	61100
81	Ospedale Civile dello "Spirito Santo"	Pescara		Italy	65100
82	Ospedale Civile di Piacenza	Piacenza		Italy	29100
83	Azienda Ospedaliera-Universitaria Pisana	Pisa		Italy	56126
84	A.O. "Santa Maria degli Angeli"	Pordenone		Italy	33170
85	Ospedale "San Carlo"di Potenza	Potenza		Italy	85100
86	Ospedale "Misericordia e Dolce"	Prato		Italy	59100
87	P.O. di Ravenna - Azienda Unità Sanitaria Locale di Ravenna	Ravenna		Italy	48100
88	A.O. "Bianchi-Melacrino-Morelli"	Reggio Calabria		Italy	89100
89	Arcispedale Santa Maria Nuova	Reggio Emilia		Italy	42100
90	Ospedale "Infermi"	Rimini		Italy	47900
91	Azienda Ospedaliera Universitaria "Policlinico Tor Vergata"	Roma		Italy	00133
92	Policlinico Umberto I	Roma		Italy	00161
93	Ospedale Fatebenefratelli "San Giovanni Calibita"	Roma		Italy	00186
94	Istituto Nazionale di Riposo e Cura per Anziani	Roma		Italy	00189
95	Istituto Dermopatico dell'Immacolata - IRCCS	Roma		Italy	MD
96	Azienda Unità Sanitaria Locale n°1 Sassari	Sassari		Italy	07100
97	Ospedale Civile di Sassari	Sassari		Italy	07100
98	A.O. della Valtellina e della Valchiavenna	Sondrio		Italy	23100
99	Ospedale San Giovanni Battista di Torino	Torino		Italy	10126
100	A.O."Ospedale di Circolo e Fondazione Macchi"	Varese		Italy	21100
101	A.O. Istituti Ospitalieri di Verona	Verona		Italy	37126