- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01989858
ITACA-S2 (Intergroup Trial in Adjuvant Chemotherapy for Adenocarcinoma of the Stomach) (ITACA-S2)
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.
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.
Study Overview
Status
Conditions
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
-
Napoli, Italy, 80131
- Fondazione "G. Pascale" Istituto Tumori di Napoli
-
-
BG
-
Bergamo, BG, Italy, 24128
- Ospedali Riuniti di Bergamo
-
Treviglio, BG, Italy, 24047
- A. O. Ospedale Treviglio-Caravaggio
-
-
BO
-
Bologna, BO, Italy, 40138
- Policlinico Sant'Orsola Malpighi
-
Bologna, BO, Italy, 40138
- A.O. Sant'Orsola Malpighi
-
-
CN
-
Cuneo, CN, Italy, 12100
- A.O. Santa Croce e Carle
-
-
CT
-
Catania, CT, Italy, 95123
- Azienda Ospedaliero-Universitaria "Policlinico-Vittorio Emanuele"
-
-
CZ
-
Catanzaro, CZ, Italy, 88100
- Policlinico Universitario Mater Domini
-
-
FI
-
Firenze, FI, Italy, 50141
- Azienda Ospedaliero- Universitaria Careggi - Firenze
-
-
MB
-
Monza, MB, Italy, 20052
- A.O. Ospedale San Gerardo
-
Vimercate, MB, Italy, 20059
- Azienda Ospedaliera di Desio e Vimercate
-
-
MI
-
Milano, MI, Italy, 20122
- Fondazione IRCCS Ospedale Maggiore Policlinico
-
Milano, MI, Italy, 20133
- Istituto Nazionale per la Cura e lo Studio dei Tumori
-
Milano, MI, Italy, 20141
- Istituto Oncologico Europeo
-
Milano, MI, Italy, 20142
- Azienda Ospedaliera "San Paolo"
-
Rozzano, MI, Italy, 20089
- Istituto Clinico Humanitas
-
Sesto San Giovanni, MI, Italy, 20099
- Casa di Cura MultiMedica
-
-
MN
-
Mantova, MN, Italy, 46100
- A. O. "Carlo Poma"
-
-
MO
-
Carpi, MO, Italy, 41012
- Ospedale "Ramazzini " di Carpi
-
-
PC
-
Piacenza, PC, Italy, 29100
- Ospedale "Guglielmo da Saliceto"
-
-
PD
-
Padova, PD, Italy, 35128
- IRCCS Istituto Oncologico Veneto
-
-
PO
-
Prato, PO, Italy, 59100
- Ospedale Misericordia e Dolce - USL 4
-
-
PU
-
Fano, PU, Italy, 61032
- Ospedale Santa Croce Fano
-
-
PZ
-
Potenza, PZ, Italy, 85100
- Azienda Ospedaliera 'San Carlo'
-
-
RE
-
Reggio Emilia, RE, Italy, 42100
- Arcispedale S. Maria Nuova Azienda Ospedaliera
-
-
RM
-
Roma, RM, Italy, 00128
- Università "Campus Bio-Medico"
-
Roma, RM, Italy, 00168
- Policlinico Universitario A. Gemelli
-
-
SO
-
Sondalo, SO, Italy, 23100
- A.O. della Valtellina e della Valchiavenna - "Ospedale E. Morelli"
-
-
TO
-
Candiolo, TO, Italy, 10060
- IRCC/FPO -Istituto per la Ricerca e la Cura del Cancro di Candiolo
-
-
VA
-
Busto Arsizio, VA, Italy, 21052
- A. O. "Ospedale di Circolo di Busto Arsizio" - Busto Arsizio (VA)
-
Saronno, VA, Italy, 21047
- A. O. Busto Arsizio - P.O. Saronno
-
Varese, VA, Italy, 21100
- A.O. Ospedale di Circolo e Fondazione Macchi
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: FACTORIAL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: peri-operative CHT (Arm A)
In peri-operative CHT arm CHT will be administered within 1 week (+3 days) after randomization, surgery will be performed after re-staging and 3+1 weeks after completion of the third cycle of CHT (approximately 13+1 weeks after randomization).
Then CHT will be re-administered 5+1 weeks after surgery.
|
CHT treatment have to be chosen between the following associations: Chemotherapy regimen containing epirubicin, cisplatin and capecitabine (EOX) E: epirubicin 50 mg/m² intravenous (iv) bolus, day 1 every 3 weeks O: oxaliplatin 130 mg/m² iv infusion, day 1 in 2-3 hours every 3 weeks X: capecitabine 625 mg/m² bis in die (bid), day 1 per os (po) continuously or Chemotherapy regimen containing epirubicin, cisplatin and 5-fluorouracil (ECF) E: epirubicin 50 mg/m² iv bolus, day 1 every 3 weeks C: cisplatin 60 mg/m² iv with standard hydration day 1 every 3 weeks F: 5FU 200 mg/m² daily by continuous infusion via central line. |
ACTIVE_COMPARATOR: post-operative CHT (Arm B)
In post-operative CHT arm, surgery will take place 3+1 weeks after randomization and CHT will be administered 5+1 weeks after surgery (approximately 8+1 weeks after randomization).
|
CHT treatment have to be chosen between the following associations: EOX E: epirubicin 50 mg/m² intravenous (iv) bolus, day 1 every 3 weeks O: oxaliplatin 130 mg/m² iv infusion, day 1 in 2-3 hours every 3 weeks X: capecitabine 625 mg/m² bis in die (bid), day 1 per os (po) continuously or ECF E: epirubicin 50 mg/m² iv bolus, day 1 every 3 weeks C: cisplatin 60 mg/m² iv with standard hydration day 1 every 3 weeks F: 5fluorouracil (5FU) 200 mg/m² daily by continuous infusion via central line. |
EXPERIMENTAL: peri-operative CHT + post-operative CHT-RTX (Arm C)
CHT 1 week (+3 days) after randomization surgery after re-staging and 3+1 weeks after completion of the third cycle of CHT CHT 5+1 weeks after surgery.
|
CHT treatment have to be chosen between the following associations:
The prescribed RTX dose to clinical target volume should be 45 gray (Gy) delivered in daily fraction of 1.8 Gy, five times per week for six weeks. RTX will be administered concurrently with CHT. The choice of the associated CHT should be between the following schedules:
|
ACTIVE_COMPARATOR: post-operative CHT + post-operative CHT-RTX (Arm D)
surgery will take place 3+1 weeks after randomization and CHT will be administered 5+1 weeks after surgery (approximately 8+1 weeks after randomization).
|
CHT treatment have to be chosen between the following associations:
The prescribed RTX dose to clinical target volume should be 45 gray (Gy) delivered in daily fraction of 1.8 Gy, five times per week for six weeks. RTX will be administered concurrently with CHT. The choice of the associated CHT should be between the following schedules:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall survival (OS)- Timing Study
Time Frame: 5 years
|
OS, defined for each patient as the time from the date of randomization to the date of death from any cause.
Patients not reported as having died at the end of the study will be censored at the date they were last known to be alive.
|
5 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Dose-intensity
Time Frame: up to 8 weeks
|
|
up to 8 weeks
|
Maximum toxicity grade
Time Frame: up to 8 weeks
|
|
up to 8 weeks
|
Disease Free Survival (DFS) - Timing Study
Time Frame: 3 years
|
DFS, defined for each patient as the time from the date of randomization to the date of local or regional relapse, distant metastasis, second primary malignancy or death from any cause, whichever comes first.
Patients not recurred, progressed or died while on study or lost to f-up will be censored at their last disease assessment date.
|
3 years
|
Relapse Free Survival (l-RFS)- RTX Study
Time Frame: 3 years
|
1-RFS, defined for each patient as the time from the date of randomization to the date of first local recurrence or death from any cause, whichever comes first. Description: 1-RFS, defined for each patient as the time from the date of randomization to the date of first local recurrence or death from any cause, whichever comes first. Patients not locally recurred or died while on study or lost to f-up will be censored at their last disease assessment date |
3 years
|
Collaborators and Investigators
Investigators
- Principal Investigator: Francesco Di Costanzo, MD, Azienda Ospedaliero- Universitaria Careggi - Firenze U.O. Medica
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2010-021052-25
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Gastric Adenocarcinoma
-
Memorial Sloan Kettering Cancer CenterRecruitingMetastatic Gastric Adenocarcinoma | Metastatic Gastroesophageal Junction Adenocarcinoma | Unresectable Gastric Adenocarcinoma | Unresectable Gastroesophageal Junction Adenocarcinoma | Metastatic Gastric Cancer | Unresectable Esophageal Cancer | Metastatic Esophageal Carcinoma | Metastatic Gastric... and other conditionsUnited States
-
National Cancer Institute (NCI)CompletedRecurrent Gastric Carcinoma | Adenocarcinoma of the Gastroesophageal Junction | Diffuse Gastric Adenocarcinoma | Gastric Intestinal Type Adenocarcinoma | Gastric Mixed AdenocarcinomaUnited States, Canada
-
City of Hope Medical CenterActive, not recruitingAdenocarcinoma of the Gastroesophageal Junction | Stage IV Gastric Cancer | Recurrent Gastric Cancer | Diffuse Adenocarcinoma of the Stomach | Intestinal Adenocarcinoma of the Stomach | Mixed Adenocarcinoma of the Stomach | Stage IIIA Gastric Cancer | Stage IIIB Gastric Cancer | Stage IIIC Gastric Cancer and other conditionsUnited States
-
University of ChicagoNational Cancer Institute (NCI)RecruitingGastric Adenocarcinoma | Esophageal Adenocarcinoma | Stage IIIA Gastric Cancer | Stage IIIB Gastric Cancer | Stage IIIC Gastric Cancer | Stage IIB Gastric Cancer | Stage IIIA Esophageal Adenocarcinoma | Stage IIIB Esophageal Adenocarcinoma | Stage IIIC Esophageal AdenocarcinomaUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)RecruitingClinical Stage III Gastric Cancer AJCC v8 | Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8 | Clinical Stage IV Gastric Cancer AJCC v8 | Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8 | Metastatic Gastric Adenocarcinoma | Metastatic Gastroesophageal Junction... and other conditionsUnited States, Puerto Rico
-
H. Lee Moffitt Cancer Center and Research InstituteActive, not recruitingGastric Cancer | Gastric Adenocarcinoma | Gastroesophageal Junction AdenocarcinomaUnited States
-
Ukrainian Society of Clinical OncologyRecruitingStomach Cancer | Gastric Cancer | Gastric Adenocarcinoma | Gastrointestinal Cancer | Gastroesophageal Junction Adenocarcinoma | Advanced Gastric Adenocarcinoma | GastroEsophageal Cancer | Stomach Neoplasm | Gastric Neoplasm | Advanced Gastric Carcinoma | Advanced Gastroesophageal Junction AdenocarcinomaUkraine
-
M.D. Anderson Cancer CenterRecruitingClinical Stage III Gastric Cancer AJCC v8 | Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8 | Clinical Stage IV Gastric Cancer AJCC v8 | Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8 | Metastatic Gastric Adenocarcinoma | Metastatic Gastroesophageal Junction... and other conditionsUnited States
-
National Cancer Institute (NCI)Not yet recruitingClinical Stage III Gastric Cancer AJCC v8 | Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8 | Clinical Stage IV Gastric Cancer AJCC v8 | Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8 | Metastatic Gastric Adenocarcinoma | Metastatic Gastroesophageal Junction... and other conditions
-
National Cancer Institute (NCI)CompletedAdenocarcinoma of the Gastroesophageal Junction | Stage IV Gastric Cancer | Recurrent Gastric Cancer | Diffuse Adenocarcinoma of the Stomach | Intestinal Adenocarcinoma of the Stomach | Mixed Adenocarcinoma of the Stomach | Stage IIIA Gastric Cancer | Stage IIIB Gastric Cancer | Stage IIIC Gastric CancerUnited States
Clinical Trials on peri-operative cht
-
Assistance Publique Hopitaux De MarseilleRecruitingComplex Congenital Heart DiseaseFrance
-
Institut Claudius RegaudBayerRecruiting
-
Sefako Makgatho Health Sciences UniversityUniversity of Cape Town; Medical Research Council, South AfricaNot yet recruitingPostoperative Complications | Covid19
-
Zhejiang Cancer HospitalUnknown
-
Chinese University of Hong KongRecruiting
-
Charite University, Berlin, GermanyKliniken Essen-MitteRecruitingFallopian Tube Cancer | Frailty | Ovary Cancer | Peritoneum CancerGermany
-
University Hospital, LilleFederation Francophone de Cancerologie Digestive; UNICANCER; Federation of Research...RecruitingSignet Ring Cell Gastric AdenocarcinomaFrance
-
MicroPort CRMCompletedHeart FailureSpain, France, Portugal, Netherlands, Germany, Italy
-
Hadassah Medical OrganizationCompletedColonic Diseases, FunctionalIsrael
-
The First Affiliated Hospital with Nanjing Medical...Not yet recruiting