Clinical trial NCT01640782: Intergroup Trial of Adjuvant Chemotherapy in Adenocarcinoma of the Stomach
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Adenocarcinoma of the Stomach
Adenocarcinoma of the Gastroesophageal Junction
Keywords: adenocarcinoma of the stomach
adenocarcinoma of the gastroesophageal junction
Lead sponsor: Mario Negri Institute for Pharmacological Research
Sponsor class: OTHER
Collaborators: name: Aventis Pharmaceuticals
name: Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente
name: Gruppo Oncologico Italiano di Ricerca Clinica
name: Gruppo Oncologico del Nord-Ovest
name: Italian Trial in Medical Oncology
name: Southern Italy Cooperative Oncology Group
name: Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS
name: Oncotech
First posted: 2012-07-16
Enrollment: 1100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: 3 years
Secondary outcomes:
measure: 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
timeFrame: 3 years
measure: Toxicity, graded according to the NCI-CTG Expanded Common Toxicity Criteria
timeFrame: 3 years
measure: Adverse events
timeFrame: 3 years
Other outcomes:
Locations:
city: Fabriano
country: Italy
facility: ASL 6 - Fabriano
state: Ancona
city: Senigallia
country: Italy
facility: Ospedale Civile di Senigallia
state: Ancona
city: Torrette di Ancona
country: Italy
facility: dell'Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I
state: Ancona
city: Ariano Irpino
country: Italy
facility: Presidio Ospedaliero di Ariano Irpino
state: Avellino
city: Treviglio
country: Italy
facility: A.O. "Ospedale Treviglio-Caravaggio"
state: Bergamo
city: Monserrato
country: Italy
facility: P.O. di Monserrato - Policlinico Universitario di Cagliari
state: Cagliari
city: Monserrato
country: Italy
facility: P.O. di Monserrato
state: Cagliari
city: Castrovillari
country: Italy
facility: Ospedale Civile "Ferrari"
state: Cosenza
city: Lamezia Terme
country: Italy
facility: Presidio Ospedaliero di Lamezia Terme
state: Cosenza
city: Paola
country: Italy
facility: Ospedale "San Francesco" di Paola
state: Cosenza
city: Alba
country: Italy
facility: P.O. S. Lazzaro
state: Cuneo
city: Antella
country: Italy
facility: Ospedale Santa Maria Annunziata
state: Firenze
city: Empoli
country: Italy
facility: Ospedale "San Giuseppe"
state: Firenze
city: Carrara
country: Italy
facility: Ospedale Civico di Carrara
state: Massa Carrara
city: Monza
country: Italy
facility: A.O "San Gerardo" di Monza
state: Milano
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
state: Milano
city: San Donato Milanese
country: Italy
facility: Ospedale IRCCS Policlinico di San Donato
state: Milano
city: Vizzolo Predabissi
country: Italy
facility: Presidio Ospedaliero "Serbelloni"di Gorgonzola
state: Milano
city: Carpi
country: Italy
facility: Ospedale "B.Ramazzini"
state: Modena
city: Pozzuoli
country: Italy
facility: Presidio Ospedaliero "Santa Maria delle Grazie"
state: Napoli
city: Este
country: Italy
facility: Ospedale Civile di Este
state: Padova
city: Città di Castello
country: Italy
facility: Ospedale di Città di Castello - ASL 1 Umbria
state: Perugia
city: Marsciano
country: Italy
facility: Ospedale di Marsciano - Servizio Oncologico
state: Perugia
city: Fano
country: Italy
facility: Ospedale "Santa Croce"
state: Pesaro
city: Penne
country: Italy
facility: Ospedale Civile "San Massimo"
state: Pesaro
city: Aviano
country: Italy
facility: Centro di Riferimento Oncologico - INT
state: Pordenone
city: Rionero in Vulture
country: Italy
facility: Centro di Riferimento Oncologico di Basilicata
state: Potenza
city: Faenza
country: Italy
facility: P.O. di Faenza
state: Ravenna
city: Lugo
country: Italy
facility: P.O. Umberto I di Lugo
state: Ravenna
city: Siderno
country: Italy
facility: Ospedale Civile di Siderno
state: Reggio Calabria
city: Vallo della Lucania
country: Italy
facility: Ospedale "San Luca"
state: Salerno
city: Candiolo
country: Italy
facility: Istituto per la Ricerca e la Cura del Cancro di Candiolo
state: Torino
city: Latisana
country: Italy
facility: Ospedale Civile di Latisana
state: Udine
city: Terni
country: Italy
facility: Azienda Ospedaliera S. Maria
state: Umbria
city: Saronno
country: Italy
facility: Presidio Ospedaliero di Saronno - A.O. "Ospedale di Circolo di Busto Arsizio"
state: Varallo
city: Busto Arsizio
country: Italy
facility: A.O. "Ospedale di Circolo di Busto Arsizio"
state: Varese
city: Legnago
country: Italy
facility: Ospedale di Legnago
state: Verona
city: Montecchio Maggiore
country: Italy
facility: Ospedale di Montecchio Maggiore
state: Vicenza
city: Arezzo
country: Italy
facility: Ospedale. S. Donato
city: Benevento
country: Italy
facility: A.O. "G. Rummo"
city: Bergamo
country: Italy
facility: Ospedali "Riuniti"
city: Biella
country: Italy
facility: Ospedale degli Infermi di Biella
city: Bologna
country: Italy
facility: Ospedale Maggiore-Bellaria
city: Bologna
country: Italy
facility: A.O.Policlinico "S.Orsola-Malpighi"
city: Brescia
country: Italy
facility: Ospedale Sant'Orsola - Fatebenefratelli
city: Brescia
country: Italy
facility: Casa di Cura Poliambulanza di Brescia
city: Brescia
country: Italy
facility: Spedali Civili
city: Catania
country: Italy
facility: P.O. Vittorio Emanuele
city: Catania
country: Italy
facility: Ospedale Garibaldi in Nesima
city: Como
country: Italy
facility: A.O. Sant'Anna
city: Como
country: Italy
facility: Ospedale "Valduce"
city: Crema
country: Italy
facility: A.O. "Ospedale Maggiore" di Crema
city: Cremona
country: Italy
facility: Azienda Ospedaliera "Istituti Ospitalieri" di Cremona
city: Cuneo
country: Italy
facility: A.O. "S.Croce e Carle"
city: Ferrara
country: Italy
facility: Azienda Ospedaliera Universitaria "S.Anna"
city: Firenze
country: Italy
facility: A.O. Universitaria Careggi
city: Forli
country: Italy
facility: A.O. "G.B.Morgagni-L.Pierantoni
city: Genova
country: Italy
facility: E.O. Ospedali Galliera di Genova
city: Genova
country: Italy
facility: Istituto Nazionale per la Ricerca sul Cancro
city: Lecco
country: Italy
facility: P.O. "A.Manzoni" di Lecco
city: Livorno
country: Italy
facility: Azienda USL 6 - P.O. Livorno
city: Lodi
country: Italy
facility: Ospedale Civile di Casalpusterlengo
city: Lucca
country: Italy
facility: Ospedale "Campo di Marte"
city: Mantova
country: Italy
facility: A.O. "C.Poma"
city: Milano
country: Italy
facility: Istituto Scientifico Universitario San Raffaele
city: Milano
country: Italy
facility: Istituto Nazionale per la cura dei tumori
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
city: Milano
country: Italy
facility: Azienda Ospedaliera "Ospedale San Carlo Borromeo"
city: Milano
country: Italy
facility: Azienda Ospedaliera "Luigi Sacco" Polo Universitario
city: Milano
country: Italy
facility: Azienda Ospedaliera "San Paolo" Polo Universitario
city: Napoli
country: Italy
facility: A.O. "D.Cotugno"
city: Napoli
country: Italy
facility: A.O.R.N. "Antonio Cardarelli"
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria "Federico II"
city: Napoli
country: Italy
facility: Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Pascale"
city: Novara
country: Italy
facility: Azienda Ospedaliera "Maggiore della Carità"
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova
city: Palermo
country: Italy
facility: Ospedali "Civico e Benfratelli - G. Di Cristina - Maurizio Ascoli"
city: Palermo
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico "Paolo Giaccone"di Palermo
city: Parma
country: Italy
facility: Azienda Ospedaliera di Parma
city: Pesaro
country: Italy
facility: A.O."Ospedale S.Salvatore"
city: Pescara
country: Italy
facility: Ospedale Civile dello "Spirito Santo"
city: Piacenza
country: Italy
facility: Ospedale Civile di Piacenza
city: Pisa
country: Italy
facility: Azienda Ospedaliera-Universitaria Pisana
city: Pordenone
country: Italy
facility: A.O. "Santa Maria degli Angeli"
city: Potenza
country: Italy
facility: Ospedale "San Carlo"di Potenza
city: Prato
country: Italy
facility: Ospedale "Misericordia e Dolce"
city: Ravenna
country: Italy
facility: P.O. di Ravenna - Azienda Unità Sanitaria Locale di Ravenna
city: Reggio Calabria
country: Italy
facility: A.O. "Bianchi-Melacrino-Morelli"
city: Reggio Emilia
country: Italy
facility: Arcispedale Santa Maria Nuova
city: Rimini
country: Italy
facility: Ospedale "Infermi"
city: Roma
country: Italy
facility: Azienda Ospedaliera Universitaria "Policlinico Tor Vergata"
city: Roma
country: Italy
facility: Policlinico Umberto I
city: Roma
country: Italy
facility: Ospedale Fatebenefratelli "San Giovanni Calibita"
city: Roma
country: Italy
facility: Istituto Nazionale di Riposo e Cura per Anziani
city: Roma
country: Italy
facility: Istituto Dermopatico dell'Immacolata - IRCCS
city: Sassari
country: Italy
facility: Azienda Unità Sanitaria Locale n°1 Sassari
city: Sassari
country: Italy
facility: Ospedale Civile di Sassari
city: Sondrio
country: Italy
facility: A.O. della Valtellina e della Valchiavenna
city: Torino
country: Italy
facility: Ospedale San Giovanni Battista di Torino
city: Varese
country: Italy
facility: A.O."Ospedale di Circolo e Fondazione Macchi"
city: Verona
country: Italy
facility: A.O. Istituti Ospitalieri di Verona
Study officials:
affiliation: Istituto Nazionale Per lo Studio e la Cura dei Tumori Milano
name: Emilio Bajetta, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bajetta E, Floriani I, Di Bartolomeo M, Labianca R, Falcone A, Di Costanzo F, Comella G, Amadori D, Pinto C, Carlomagno C, Nitti D, Daniele B, Mini E, Poli D, Santoro A, Mosconi S, Casaretti R, Boni C, Pinotti G, Bidoli P, Landi L, Rosati G, Ravaioli A, Cantore M, Di Fabio F, Aitini E, Marchet A; ITACA-S (Intergroup Trial of Adjuvant Chemotherapy in Adenocarcinoma of the Stomach Trial) Study Group. Randomized trial on adjuvant treatment with FOLFIRI followed by docetaxel and cisplatin versus 5-fluorouracil and folinic acid for radically resected gastric cancer. Ann Oncol. 2014 Jul;25(7):1373-1378. doi: 10.1093/annonc/mdu146. Epub 2014 Apr 12.