Intergroup Trial of Adjuvant Chemotherapy in Adenocarcinoma of the Stomach

NCT ID: NCT01640782

Last Updated: 2014-07-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-02-28
• Study Completion Date: 2013-01-31

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.

Conditions

Adenocarcinoma of the Stomach; Adenocarcinoma of the Gastroesophageal Junction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Sequential regimen

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

Group Type: EXPERIMENTAL

Irinotecan, Leucovorin, 5-Fluorouracil, Docetaxel, Cisplatin

Intervention Type: DRUG

• 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.

De Gramont regimen

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

Group Type: ACTIVE_COMPARATOR

Leucovorin, 5-Fluorouracil

Intervention Type: DRUG

• 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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Aventis Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente

OTHER

Sponsor Role: collaborator

Gruppo Oncologico Italiano di Ricerca Clinica

OTHER

Sponsor Role: collaborator

Gruppo Oncologico del Nord-Ovest

OTHER

Sponsor Role: collaborator

Italian Trial in Medical Oncology

OTHER

Sponsor Role: collaborator

Southern Italy Cooperative Oncology Group

OTHER

Sponsor Role: collaborator

Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS

OTHER

Sponsor Role: collaborator

Oncotech

INDUSTRY

Sponsor Role: collaborator

Mario Negri Institute for Pharmacological Research

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Emilio Bajetta, MD

Role: PRINCIPAL_INVESTIGATOR

Istituto Nazionale Per lo Studio e la Cura dei Tumori Milano

Locations

ASL 6 - Fabriano

Fabriano, Ancona, Italy

Ospedale Civile di Senigallia

Senigallia, Ancona, Italy

dell'Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I

Torrette Di Ancona, Ancona, Italy

Ospedale. S. Donato

Arezzo, Arezzo, Italy

Presidio Ospedaliero di Ariano Irpino

Ariano Irpino, Avellino, Italy

A.O. "G. Rummo"

Benevento, Benevento, Italy

Ospedali "Riuniti"

Bergamo, Bergamo, Italy

A.O. "Ospedale Treviglio-Caravaggio"

Treviglio, Bergamo, Italy

Ospedale degli Infermi di Biella

Biella, Biella, Italy

Ospedale Maggiore-Bellaria

Bologna, Bologna, Italy

A.O.Policlinico "S.Orsola-Malpighi"

Bologna, Bologna, Italy

Ospedale Sant'Orsola - Fatebenefratelli

Brescia, Brescia, Italy

Casa di Cura Poliambulanza di Brescia

Brescia, Brescia, Italy

Spedali Civili

Brescia, Brescia, Italy

P.O. di Monserrato - Policlinico Universitario di Cagliari

Monserrato, Cagliari, Italy

P.O. di Monserrato

Monserrato, Cagliari, Italy

P.O. Vittorio Emanuele

Catania, Catania, Italy

Ospedale Garibaldi in Nesima

Catania, Catania, Italy

A.O. Sant'Anna

Como, Como, Italy

Ospedale "Valduce"

Como, Como, Italy

Ospedale Civile "Ferrari"

Castrovillari, Cosenza, Italy

Presidio Ospedaliero di Lamezia Terme

Lamezia Terme, Cosenza, Italy

Ospedale "San Francesco" di Paola

Paola, Cosenza, Italy

A.O. "Ospedale Maggiore" di Crema

Crema, Crema, Italy

Azienda Ospedaliera "Istituti Ospitalieri" di Cremona

Cremona, Cremona, Italy

P.O. S. Lazzaro

Alba, Cuneo, Italy

A.O. "S.Croce e Carle"

Cuneo, Cuneo, Italy

Azienda Ospedaliera Universitaria "S.Anna"

Ferrara, Ferrara, Italy

Ospedale Santa Maria Annunziata

Antella, Firenze, Italy

Ospedale "San Giuseppe"

Empoli, Firenze, Italy

A.O. Universitaria Careggi

Florence, Firenze, Italy

A.O. "G.B.Morgagni-L.Pierantoni

Forlì, Forli, Italy

E.O. Ospedali Galliera di Genova

Genova, Genova, Italy

Istituto Nazionale per la Ricerca sul Cancro

Genova, Genova, Italy

P.O. "A.Manzoni" di Lecco

Lecco, Lecco, Italy

Azienda USL 6 - P.O. Livorno

Livorno, Livorno, Italy

Ospedale Civile di Casalpusterlengo

Lodi, Lodi, Italy

Ospedale "Campo di Marte"

Lucca, Lucca, Italy

A.O. "C.Poma"

Mantova, Mantova, Italy

Ospedale Civico di Carrara

Carrara, Massa Carrara, Italy

Istituto Scientifico Universitario San Raffaele

Milan, Milano, Italy

Istituto Nazionale per la cura dei tumori

Milan, Milano, Italy

Istituto Europeo di Oncologia

Milan, Milano, Italy

Azienda Ospedaliera "Ospedale San Carlo Borromeo"

Milan, Milano, Italy

Azienda Ospedaliera "Luigi Sacco" Polo Universitario

Milan, Milano, Italy

Azienda Ospedaliera "San Paolo" Polo Universitario

Milan, Milano, 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

A.O. "D.Cotugno"

Napoli, Napoli, Italy

A.O.R.N. "Antonio Cardarelli"

Napoli, Napoli, Italy

Azienda Ospedaliera Universitaria "Federico II"

Napoli, Napoli, Italy

Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Pascale"

Napoli, Napoli, Italy

Presidio Ospedaliero "Santa Maria delle Grazie"

Pozzuoli, Napoli, Italy

Azienda Ospedaliera "Maggiore della Carità"

Novara, Novara, Italy

Ospedale Civile di Este

Este, Padova, Italy

Azienda Ospedaliera di Padova

Padua, Padova, Italy

Ospedali "Civico e Benfratelli - G. Di Cristina - Maurizio Ascoli"

Palermo, Palermo, Italy

Azienda Ospedaliera Universitaria Policlinico "Paolo Giaccone"di Palermo

Palermo, Palermo, Italy

Azienda Ospedaliera di Parma

Parma, Parma, 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

Ospedale Civile "San Massimo"

Penne, Pesaro, Italy

A.O."Ospedale S.Salvatore"

Pesaro, Pesaro, Italy

Ospedale Civile dello "Spirito Santo"

Pescara, Pescara, Italy

Ospedale Civile di Piacenza

Piacenza, Piacenza, Italy

Azienda Ospedaliera-Universitaria Pisana

Pisa, Pisa, Italy

Centro di Riferimento Oncologico - INT

Aviano, Pordenone, Italy

A.O. "Santa Maria degli Angeli"

Pordenone, Pordenone, Italy

Ospedale "San Carlo"di Potenza

Potenza, Potenza, Italy

Centro di Riferimento Oncologico di Basilicata

Rionero in Vulture, Potenza, Italy

Ospedale "Misericordia e Dolce"

Prato, Prato, Italy

P.O. di Faenza

Faenza, Ravenna, Italy

P.O. Umberto I di Lugo

Lugo, Ravenna, Italy

P.O. di Ravenna - Azienda Unità Sanitaria Locale di Ravenna

Ravenna, Ravenna, Italy

A.O. "Bianchi-Melacrino-Morelli"

Reggio Calabria, Reggio Calabria, Italy

Ospedale Civile di Siderno

Siderno, Reggio Calabria, Italy

Arcispedale Santa Maria Nuova

Reggio Emilia, Reggio Emilia, Italy

Ospedale "Infermi"

Rimini, Rimini, Italy

Azienda Ospedaliera Universitaria "Policlinico Tor Vergata"

Roma, Roma, Italy

Policlinico Umberto I

Roma, Roma, Italy

Ospedale Fatebenefratelli "San Giovanni Calibita"

Roma, Roma, Italy

Istituto Nazionale di Riposo e Cura per Anziani

Roma, Roma, Italy

Istituto Dermopatico dell'Immacolata - IRCCS

Roma, Roma, Italy

Ospedale "San Luca"

Vallo della Lucania, Salerno, Italy

Azienda Unità Sanitaria Locale n°1 Sassari

Sassari, Sassari, Italy

Ospedale Civile di Sassari

Sassari, Sassari, Italy

A.O. della Valtellina e della Valchiavenna

Sondrio, Sondrio, Italy

Istituto per la Ricerca e la Cura del Cancro di Candiolo

Candiolo, Torino, Italy

Ospedale San Giovanni Battista di Torino

Torino, Torino, Italy

Ospedale Civile di Latisana

Latisana, Udine, Italy

Azienda Ospedaliera S. Maria

Terni, Umbria, Italy

Presidio Ospedaliero di Saronno - A.O. "Ospedale di Circolo di Busto Arsizio"

Saronno, Varallo, Italy

A.O. "Ospedale di Circolo di Busto Arsizio"

Busto Arsizio, Varese, Italy

A.O."Ospedale di Circolo e Fondazione Macchi"

Varese, Varese, Italy

Ospedale di Legnago

Legnago, Verona, Italy

A.O. Istituti Ospitalieri di Verona

Verona, Verona, Italy

Ospedale di Montecchio Maggiore

Montecchio Maggiore, Vicenza, Italy

Countries

Italy

References

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.

Reference Type: DERIVED

PMID: 24728035 (View on PubMed)

Other Identifiers

ITACA-S

Identifier Type: -

Identifier Source: org_study_id