Intergroup Trial of Adjuvant Chemotherapy in Adenocarcinoma of the Stomach

Adenocarcinoma of the Gastroesophageal Junction Clinical Trial

— ITACA-S  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01640782
• Other study ID #: ITACA-S
• Status: Completed
• Phase: Phase 3
• First received: July 9, 2012
• Last updated: July 17, 2014
• Start date: February 2005
• Est. completion date: January 2013

Study information

• Verified date: December 2013
• Source: Mario Negri Institute for Pharmacological Research
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: The Italian Medicines Agency
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 1100
• Est. completion date: January 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of the Gastroesophageal Junction
• Adenocarcinoma of the Stomach
• Esophageal Neoplasms

Intervention

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.
• 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.

Locations

Country	Name	City	State
Italy	P.O. S. Lazzaro	Alba	Cuneo
Italy	Ospedale Santa Maria Annunziata	Antella	Firenze
Italy	Ospedale. S. Donato	Arezzo
Italy	Presidio Ospedaliero di Ariano Irpino	Ariano Irpino	Avellino
Italy	Centro di Riferimento Oncologico - INT	Aviano	Pordenone
Italy	A.O. "G. Rummo"	Benevento
Italy	Ospedali "Riuniti"	Bergamo
Italy	Ospedale degli Infermi di Biella	Biella
Italy	A.O.Policlinico "S.Orsola-Malpighi"	Bologna
Italy	Ospedale Maggiore-Bellaria	Bologna
Italy	Casa di Cura Poliambulanza di Brescia	Brescia
Italy	Ospedale Sant'Orsola - Fatebenefratelli	Brescia
Italy	Spedali Civili	Brescia
Italy	A.O. "Ospedale di Circolo di Busto Arsizio"	Busto Arsizio	Varese
Italy	Istituto per la Ricerca e la Cura del Cancro di Candiolo	Candiolo	Torino
Italy	Ospedale "B.Ramazzini"	Carpi	Modena
Italy	Ospedale Civico di Carrara	Carrara	Massa Carrara
Italy	Ospedale Civile "Ferrari"	Castrovillari	Cosenza
Italy	Ospedale Garibaldi in Nesima	Catania
Italy	P.O. Vittorio Emanuele	Catania
Italy	Ospedale di Città di Castello - ASL 1 Umbria	Città di Castello	Perugia
Italy	A.O. Sant'Anna	Como
Italy	Ospedale "Valduce"	Como
Italy	A.O. "Ospedale Maggiore" di Crema	Crema
Italy	Azienda Ospedaliera "Istituti Ospitalieri" di Cremona	Cremona
Italy	A.O. "S.Croce e Carle"	Cuneo
Italy	Ospedale "San Giuseppe"	Empoli	Firenze
Italy	Ospedale Civile di Este	Este	Padova
Italy	ASL 6 - Fabriano	Fabriano	Ancona
Italy	P.O. di Faenza	Faenza	Ravenna
Italy	Ospedale "Santa Croce"	Fano	Pesaro
Italy	Azienda Ospedaliera Universitaria "S.Anna"	Ferrara
Italy	A.O. Universitaria Careggi	Firenze
Italy	A.O. "G.B.Morgagni-L.Pierantoni	Forli
Italy	E.O. Ospedali Galliera di Genova	Genova
Italy	Istituto Nazionale per la Ricerca sul Cancro	Genova
Italy	Presidio Ospedaliero di Lamezia Terme	Lamezia Terme	Cosenza
Italy	Ospedale Civile di Latisana	Latisana	Udine
Italy	P.O. "A.Manzoni" di Lecco	Lecco
Italy	Ospedale di Legnago	Legnago	Verona
Italy	Azienda USL 6 - P.O. Livorno	Livorno
Italy	Ospedale Civile di Casalpusterlengo	Lodi
Italy	Ospedale "Campo di Marte"	Lucca
Italy	P.O. Umberto I di Lugo	Lugo	Ravenna
Italy	A.O. "C.Poma"	Mantova
Italy	Ospedale di Marsciano - Servizio Oncologico	Marsciano	Perugia
Italy	Azienda Ospedaliera "Luigi Sacco" Polo Universitario	Milano
Italy	Azienda Ospedaliera "Ospedale San Carlo Borromeo"	Milano
Italy	Azienda Ospedaliera "San Paolo" Polo Universitario	Milano
Italy	Istituto Europeo di Oncologia	Milano
Italy	Istituto Nazionale per la cura dei tumori	Milano
Italy	Istituto Scientifico Universitario San Raffaele	Milano
Italy	P.O. di Monserrato	Monserrato	Cagliari
Italy	P.O. di Monserrato - Policlinico Universitario di Cagliari	Monserrato	Cagliari
Italy	Ospedale di Montecchio Maggiore	Montecchio Maggiore	Vicenza
Italy	A.O "San Gerardo" di Monza	Monza	Milano
Italy	A.O. "D.Cotugno"	Napoli
Italy	A.O.R.N. "Antonio Cardarelli"	Napoli
Italy	Azienda Ospedaliera Universitaria "Federico II"	Napoli
Italy	Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Pascale"	Napoli
Italy	Azienda Ospedaliera "Maggiore della Carità"	Novara
Italy	Azienda Ospedaliera di Padova	Padova
Italy	Azienda Ospedaliera Universitaria Policlinico "Paolo Giaccone"di Palermo	Palermo
Italy	Ospedali "Civico e Benfratelli - G. Di Cristina - Maurizio Ascoli"	Palermo
Italy	Ospedale "San Francesco" di Paola	Paola	Cosenza
Italy	Azienda Ospedaliera di Parma	Parma
Italy	Ospedale Civile "San Massimo"	Penne	Pesaro
Italy	A.O."Ospedale S.Salvatore"	Pesaro
Italy	Ospedale Civile dello "Spirito Santo"	Pescara
Italy	Ospedale Civile di Piacenza	Piacenza
Italy	Azienda Ospedaliera-Universitaria Pisana	Pisa
Italy	A.O. "Santa Maria degli Angeli"	Pordenone
Italy	Ospedale "San Carlo"di Potenza	Potenza
Italy	Presidio Ospedaliero "Santa Maria delle Grazie"	Pozzuoli	Napoli
Italy	Ospedale "Misericordia e Dolce"	Prato
Italy	P.O. di Ravenna - Azienda Unità Sanitaria Locale di Ravenna	Ravenna
Italy	A.O. "Bianchi-Melacrino-Morelli"	Reggio Calabria
Italy	Arcispedale Santa Maria Nuova	Reggio Emilia
Italy	Ospedale "Infermi"	Rimini
Italy	Centro di Riferimento Oncologico di Basilicata	Rionero in Vulture	Potenza
Italy	Azienda Ospedaliera Universitaria "Policlinico Tor Vergata"	Roma
Italy	Istituto Dermopatico dell'Immacolata - IRCCS	Roma
Italy	Istituto Nazionale di Riposo e Cura per Anziani	Roma
Italy	Ospedale Fatebenefratelli "San Giovanni Calibita"	Roma
Italy	Policlinico Umberto I	Roma
Italy	Istituto Clinico Humanitas	Rozzano	Milano
Italy	Ospedale IRCCS Policlinico di San Donato	San Donato Milanese	Milano
Italy	Presidio Ospedaliero di Saronno - A.O. "Ospedale di Circolo di Busto Arsizio"	Saronno	Varallo
Italy	Azienda Unità Sanitaria Locale n°1 Sassari	Sassari
Italy	Ospedale Civile di Sassari	Sassari
Italy	Ospedale Civile di Senigallia	Senigallia	Ancona
Italy	Ospedale Civile di Siderno	Siderno	Reggio Calabria
Italy	A.O. della Valtellina e della Valchiavenna	Sondrio
Italy	Azienda Ospedaliera S. Maria	Terni	Umbria
Italy	Ospedale San Giovanni Battista di Torino	Torino
Italy	dell'Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I	Torrette di Ancona	Ancona
Italy	A.O. "Ospedale Treviglio-Caravaggio"	Treviglio	Bergamo
Italy	Ospedale "San Luca"	Vallo della Lucania	Salerno
Italy	A.O."Ospedale di Circolo e Fondazione Macchi"	Varese
Italy	A.O. Istituti Ospitalieri di Verona	Verona
Italy	Presidio Ospedaliero "Serbelloni"di Gorgonzola	Vizzolo Predabissi	Milano

Sponsors (9)

Lead Sponsor	Collaborator
Mario Negri Institute for Pharmacological Research	Aventis Pharmaceuticals, Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente, Gruppo Oncologico del Nord-Ovest, Gruppo Oncologico Italiano di Ricerca Clinica, Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori, Italian Trial in Medical Oncology, Oncotech, Southern Italy Cooperative Oncology Group

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	Yes
Secondary	Toxicity, graded according to the NCI-CTG Expanded Common Toxicity Criteria		3 years	Yes
Secondary	Adverse events		3 years	Yes