Clinical trial NCT01989858: ITACA-S2 (Intergroup Trial in Adjuvant Chemotherapy for Adenocarcinoma of the Stomach)
Official title: ITACA-S2(Intergroup Trial in Adjuvant Chemotherapy for Adenocarcinoma of the Stomach:Comparison of the Efficacy of a Peri-operative Versus a Post-operative Chemotherapy Treatment in Patients With Operable Gastric Cancer and Assessment of the Benefit of a Post-operative Chemo-radiotherapy.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Gastric Adenocarcinoma
Keywords: localized gastric adenocarcinoma, operable considered.
Lead sponsor: Mario Negri Institute for Pharmacological Research
Sponsor class: OTHER
First posted: 2013-11-21
Enrollment: 1180
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: The study addresses two primary questions, according to its factorial design:

* to compare the efficacy in terms of overall survival (OS) of a peri-operative vs. a post-operative chemotherapy (CHT) treatment, irrespectively of the presence of a post-surgical chemo-radiotherapy (CHT-RTX) (Timing Study);
* to compare the efficacy in terms of relapse free survival (l-RFS) of a post-surgical CHT-RTX treatment vs. no other treatment, irrespectively of the timing of CHT (RTX Study).

The study has a 2x2 factorial design, thus consisting of two independent, following specific eligibility criteria and with different randomization scheme studies, the Timing Study and the RTX Study.

Both studies are Italian, multicentre, open-label, randomized, superiority, phase III trials conducted in patients with histologically confirmed, localized gastric adenocarcinoma, which is considered operable.

In the Timing Study patients fulfilling the eligibility criteria will be randomized with a 1:1 ratio to receive:

* peri-operative CHT (Arm A) or
* post-operative CHT (Arm B) Once randomized in the Timing Study, patients may also be randomized in the RTX

Study to receive in addition to CHT a post-operative CHT-RTX treatment or no other treatment. This is possible since the randomization will be done in two steps: the first for the Timing Study for all the participating centres (peri-operative CHT vs. post-operative CHT) and the second one for the RTX Study, only for those centres with the radiotherapist willing and able to participate (post- surgical CHT-RTX vs. no other treatment). Thus the following four arms will be generated:

* peri-operative CHT (Arm A)
* post-operative CHT (Arm B)
* peri-operative CHT + post-operative CHT-RTX (Arm C)
* post-operative CHT + post-operative CHT-RTX (Arm D) The study will be conducted in more than one hundred experimental centres. Follow-up F(-up) procedures and timing of the visits will be consistent with current clinical practice.

Based on case-mix of sample 1000-1180 patients are needed in the Timing study and 420-520 in the RTX study.


Eligibility criteria: Inclusion Criteria:

* age \>18 years
* Eastern Cooperative Oncology Group - Performance Status (ECOG-PS) 0-1
* T3 or T4 carcinoma without lymphnode involvement (N0) and any T-stage with (N+) lymphnode involvement
* no distant metastases (M0)
* fitness to receive CHT and CHT-RTX
* no peripheral neuropathy greater than grade 1
* absence of peritoneal carcinomatosis
* written informed consents (one for each trial) given before the randomization, according to International Conference on Harmonisation/Good Clinical Practice (ICH/GCP)

Exclusion Criteria:

* adenocarcinoma of the gastro-esophageal junction
* previous CHT or RTX
* abnormal haematological, hepatic or renal functions, assessed within 7 days prior to randomization
* lymphnode metastases (biopsy proof, if possible) outside the loco-regional field, such as supraclavicular, mediastinal or para-aortic nodes
* positive peritoneal cytology
* clinical significant (i.e. active) cardiovascular disease for example cerebrovascular accidents (≤ 6 months), myocardial infarction (≤ 6 months), instable angina, New York Heart Association grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication
* lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, or inability to take oral medication
* history or presence of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or patients at high risk from treatment complications
* pregnancy or breast feeding. Women of childbearing potential and their parents must be willing to practice acceptable methods of birth control to prevent pregnancy
* presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and f-up schedule

Primary outcomes:
measure: Overall survival (OS)- Timing Study
timeFrame: 5 years
Secondary outcomes:
measure: Dose-intensity
timeFrame: up to 8 weeks
measure: Maximum toxicity grade
timeFrame: up to 8 weeks
measure: Disease Free Survival (DFS) - Timing Study
timeFrame: 3 years
measure: Relapse Free Survival (l-RFS)- RTX Study
timeFrame: 3 years
Other outcomes:
Locations:
city: Bergamo
country: Italy
facility: Ospedali Riuniti di Bergamo
state: BG
city: Treviglio
country: Italy
facility: A. O. Ospedale Treviglio-Caravaggio
state: BG
city: Bologna
country: Italy
facility: A.O. Sant'Orsola Malpighi
state: BO
city: Bologna
country: Italy
facility: Policlinico Sant'Orsola Malpighi
state: BO
city: Cuneo
country: Italy
facility: A.O. Santa Croce e Carle
state: CN
city: Catania
country: Italy
facility: Azienda Ospedaliero-Universitaria "Policlinico-Vittorio Emanuele"
state: CT
city: Catanzaro
country: Italy
facility: Policlinico Universitario Mater Domini
state: CZ
city: Firenze
country: Italy
facility: Azienda Ospedaliero- Universitaria Careggi - Firenze
state: FI
city: Monza
country: Italy
facility: A.O. Ospedale San Gerardo
state: MB
city: Vimercate
country: Italy
facility: Azienda Ospedaliera di Desio e Vimercate
state: MB
city: Milano
country: Italy
facility: Fondazione IRCCS Ospedale Maggiore Policlinico
state: MI
city: Milano
country: Italy
facility: Istituto Nazionale per la Cura e lo Studio dei Tumori
state: MI
city: Milano
country: Italy
facility: Istituto Oncologico Europeo
state: MI
city: Milano
country: Italy
facility: Azienda Ospedaliera "San Paolo"
state: MI
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
state: MI
city: Sesto San Giovanni
country: Italy
facility: Casa di Cura MultiMedica
state: MI
city: Mantova
country: Italy
facility: A. O. "Carlo Poma"
state: MN
city: Carpi
country: Italy
facility: Ospedale "Ramazzini " di Carpi
state: MO
city: Piacenza
country: Italy
facility: Ospedale "Guglielmo da Saliceto"
state: PC
city: Padova
country: Italy
facility: IRCCS Istituto Oncologico Veneto
state: PD
city: Prato
country: Italy
facility: Ospedale Misericordia e Dolce - USL 4
state: PO
city: Fano
country: Italy
facility: Ospedale Santa Croce Fano
state: PU
city: Potenza
country: Italy
facility: Azienda Ospedaliera 'San Carlo'
state: PZ
city: Reggio Emilia
country: Italy
facility: Arcispedale S. Maria Nuova Azienda Ospedaliera
state: RE
city: Roma
country: Italy
facility: Università "Campus Bio-Medico"
state: RM
city: Roma
country: Italy
facility: Policlinico Universitario A. Gemelli
state: RM
city: Sondalo
country: Italy
facility: A.O. della Valtellina e della Valchiavenna - "Ospedale E. Morelli"
state: SO
city: Candiolo
country: Italy
facility: IRCC/FPO -Istituto per la Ricerca e la Cura del Cancro di Candiolo
state: TO
city: Busto Arsizio
country: Italy
facility: A. O. "Ospedale di Circolo di Busto Arsizio" - Busto Arsizio (VA)
state: VA
city: Saronno
country: Italy
facility: A. O. Busto Arsizio - P.O. Saronno
state: VA
city: Varese
country: Italy
facility: A.O. Ospedale di Circolo e Fondazione Macchi
state: VA
city: Napoli
country: Italy
facility: Fondazione "G. Pascale" Istituto Tumori di Napoli
Study officials:
affiliation: Azienda Ospedaliero- Universitaria Careggi - Firenze U.O. Medica
name: Francesco Di Costanzo, MD
role: PRINCIPAL_INVESTIGATOR
References: