Intergroup Trial of Adjuvant Chemotherapy in Adenocarcinoma of the Stomach
- Conditions
- Adenocarcinoma of the Gastroesophageal JunctionAdenocarcinoma of the Stomach
- Interventions
- Drug: Irinotecan, Leucovorin, 5-Fluorouracil, Docetaxel, Cisplatin
- Registration Number
- NCT01640782
- Lead Sponsor
- Mario Negri Institute for Pharmacological Research
- 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.
- Detailed Description
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.
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1100
-
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.
-
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Sequential regimen Irinotecan, Leucovorin, 5-Fluorouracil, Docetaxel, Cisplatin Sequential treatment with CPT-11 plus Fluorouracil (FU), folinic acid (LV) and Docetaxel (TXT) plus Cisplatin (CDDP) De Gramont regimen Leucovorin, 5-Fluorouracil Fluorouracil (5-FU), folinic acid (LV)
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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 Adverse events 3 years Toxicity, graded according to the NCI-CTG Expanded Common Toxicity Criteria 3 years
Trial Locations
- Locations (101)
ASL 6 - Fabriano
🇮🇹Fabriano, Ancona, Italy
Ospedale Civile di Senigallia
🇮🇹Senigallia, Ancona, Italy
Presidio Ospedaliero di Ariano Irpino
🇮🇹Ariano Irpino, Avellino, Italy
P.O. di Monserrato - Policlinico Universitario di Cagliari
🇮🇹Monserrato, Cagliari, Italy
P.O. di Monserrato
🇮🇹Monserrato, Cagliari, Italy
Ospedale Civile "Ferrari"
🇮🇹Castrovillari, Cosenza, Italy
Presidio Ospedaliero di Lamezia Terme
🇮🇹Lamezia Terme, Cosenza, Italy
Ospedale "San Giuseppe"
🇮🇹Empoli, Firenze, Italy
Ospedale Civico di Carrara
🇮🇹Carrara, Massa Carrara, Italy
A.O "San Gerardo" di Monza
🇮🇹Monza, Milano, Italy
Istituto Clinico Humanitas
🇮🇹Rozzano, Milano, Italy
Ospedale IRCCS Policlinico di San Donato
🇮🇹San Donato Milanese, Milano, Italy
Presidio Ospedaliero "Serbelloni"di Gorgonzola
🇮🇹Vizzolo Predabissi, Milano, Italy
Ospedale "B.Ramazzini"
🇮🇹Carpi, Modena, Italy
Presidio Ospedaliero "Santa Maria delle Grazie"
🇮🇹Pozzuoli, Napoli, Italy
Ospedale Civile di Este
🇮🇹Este, Padova, Italy
Ospedale di Città di Castello - ASL 1 Umbria
🇮🇹Città di Castello, Perugia, Italy
Ospedale di Marsciano - Servizio Oncologico
🇮🇹Marsciano, Perugia, Italy
Ospedale "Santa Croce"
🇮🇹Fano, Pesaro, Italy
Centro di Riferimento Oncologico - INT
🇮🇹Aviano, Pordenone, Italy
Centro di Riferimento Oncologico di Basilicata
🇮🇹Rionero in Vulture, Potenza, Italy
Ospedale Civile di Siderno
🇮🇹Siderno, Reggio Calabria, Italy
Ospedale "San Luca"
🇮🇹Vallo della Lucania, Salerno, Italy
Istituto per la Ricerca e la Cura del Cancro di Candiolo
🇮🇹Candiolo, Torino, Italy
Ospedale Civile di Latisana
🇮🇹Latisana, Udine, Italy
Presidio Ospedaliero di Saronno - A.O. "Ospedale di Circolo di Busto Arsizio"
🇮🇹Saronno, Varallo, Italy
Ospedale di Montecchio Maggiore
🇮🇹Montecchio Maggiore, Vicenza, Italy
Ospedale. S. Donato
🇮🇹Arezzo, Italy
A.O. "Ospedale di Circolo di Busto Arsizio"
🇮🇹Busto Arsizio, Varese, Italy
A.O. "G. Rummo"
🇮🇹Benevento, Italy
Ospedali "Riuniti"
🇮🇹Bergamo, Italy
Ospedale degli Infermi di Biella
🇮🇹Biella, Italy
Ospedale Sant'Orsola - Fatebenefratelli
🇮🇹Brescia, Italy
Spedali Civili
🇮🇹Brescia, Italy
P.O. Vittorio Emanuele
🇮🇹Catania, Italy
Ospedale Garibaldi in Nesima
🇮🇹Catania, Italy
A.O. Sant'Anna
🇮🇹Como, Italy
A.O. "Ospedale Maggiore" di Crema
🇮🇹Crema, Italy
A.O. "G.B.Morgagni-L.Pierantoni
🇮🇹Forli, Italy
E.O. Ospedali Galliera di Genova
🇮🇹Genova, Italy
Azienda Ospedaliera "Maggiore della Carità "
🇮🇹Novara, Italy
Azienda Ospedaliera di Parma
🇮🇹Parma, Italy
Istituto Nazionale per la Ricerca sul Cancro
🇮🇹Genova, Italy
P.O. "A.Manzoni" di Lecco
🇮🇹Lecco, Italy
Azienda USL 6 - P.O. Livorno
🇮🇹Livorno, Italy
A.O. "C.Poma"
🇮🇹Mantova, Italy
A.O. "Santa Maria degli Angeli"
🇮🇹Pordenone, Italy
Ospedale "San Carlo"di Potenza
🇮🇹Potenza, Italy
P.O. di Ravenna - Azienda Unità Sanitaria Locale di Ravenna
🇮🇹Ravenna, Italy
Istituto Nazionale di Riposo e Cura per Anziani
🇮🇹Roma, Italy
Ospedale Civile di Casalpusterlengo
🇮🇹Lodi, Italy
Ospedale "Campo di Marte"
🇮🇹Lucca, Italy
Azienda Ospedaliera "Ospedale San Carlo Borromeo"
🇮🇹Milano, Italy
Ospedale "Misericordia e Dolce"
🇮🇹Prato, Italy
Istituto Nazionale per la cura dei tumori
🇮🇹Milano, Italy
Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Pascale"
🇮🇹Napoli, Italy
Istituto Europeo di Oncologia
🇮🇹Milano, Italy
Azienda Ospedaliera Universitaria "Federico II"
🇮🇹Napoli, Italy
Arcispedale Santa Maria Nuova
🇮🇹Reggio Emilia, Italy
Azienda Ospedaliera di Padova
🇮🇹Padova, Italy
Ospedali "Civico e Benfratelli - G. Di Cristina - Maurizio Ascoli"
🇮🇹Palermo, Italy
Azienda Ospedaliera Universitaria Policlinico "Paolo Giaccone"di Palermo
🇮🇹Palermo, Italy
A.O."Ospedale S.Salvatore"
🇮🇹Pesaro, Italy
Ospedale Civile dello "Spirito Santo"
🇮🇹Pescara, Italy
Ospedale "Infermi"
🇮🇹Rimini, Italy
Ospedale Civile di Sassari
🇮🇹Sassari, Italy
Azienda Ospedaliera Universitaria "Policlinico Tor Vergata"
🇮🇹Roma, Italy
Policlinico Umberto I
🇮🇹Roma, Italy
Azienda Unità Sanitaria Locale n°1 Sassari
🇮🇹Sassari, Italy
A.O. della Valtellina e della Valchiavenna
🇮🇹Sondrio, Italy
A.O."Ospedale di Circolo e Fondazione Macchi"
🇮🇹Varese, Italy
A.O. Istituti Ospitalieri di Verona
🇮🇹Verona, Italy
Ospedale "San Francesco" di Paola
🇮🇹Paola, Cosenza, Italy
A.O.Policlinico "S.Orsola-Malpighi"
🇮🇹Bologna, Italy
Ospedale Santa Maria Annunziata
🇮🇹Antella, Firenze, Italy
Casa di Cura Poliambulanza di Brescia
🇮🇹Brescia, Italy
Azienda Ospedaliera S. Maria
🇮🇹Terni, Umbria, Italy
dell'Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I
🇮🇹Torrette di Ancona, Ancona, Italy
Ospedale "Valduce"
🇮🇹Como, Italy
Azienda Ospedaliera "Luigi Sacco" Polo Universitario
🇮🇹Milano, Italy
Ospedale Fatebenefratelli "San Giovanni Calibita"
🇮🇹Roma, Italy
Ospedale Civile di Piacenza
🇮🇹Piacenza, Italy
Azienda Ospedaliera-Universitaria Pisana
🇮🇹Pisa, Italy
A.O. "Bianchi-Melacrino-Morelli"
🇮🇹Reggio Calabria, Italy
Ospedale San Giovanni Battista di Torino
🇮🇹Torino, Italy
Azienda Ospedaliera Universitaria "S.Anna"
🇮🇹Ferrara, Italy
Istituto Scientifico Universitario San Raffaele
🇮🇹Milano, Italy
A.O. "Ospedale Treviglio-Caravaggio"
🇮🇹Treviglio, Bergamo, Italy
Ospedale di Legnago
🇮🇹Legnago, Verona, Italy
P.O. S. Lazzaro
🇮🇹Alba, Cuneo, Italy
Ospedale Maggiore-Bellaria
🇮🇹Bologna, Italy
Ospedale Civile "San Massimo"
🇮🇹Penne, Pesaro, Italy
P.O. di Faenza
🇮🇹Faenza, Ravenna, Italy
P.O. Umberto I di Lugo
🇮🇹Lugo, Ravenna, Italy
Azienda Ospedaliera "Istituti Ospitalieri" di Cremona
🇮🇹Cremona, Italy
A.O. "S.Croce e Carle"
🇮🇹Cuneo, Italy
A.O. Universitaria Careggi
🇮🇹Firenze, Italy
Azienda Ospedaliera "San Paolo" Polo Universitario
🇮🇹Milano, Italy
A.O. "D.Cotugno"
🇮🇹Napoli, Italy
A.O.R.N. "Antonio Cardarelli"
🇮🇹Napoli, Italy
Istituto Dermopatico dell'Immacolata - IRCCS
🇮🇹Roma, Italy