ITACA-S2 (Intergroup Trial in Adjuvant Chemotherapy for Adenocarcinoma of the Stomach)

Gastric Adenocarcinoma Clinical Trial

— ITACA-S2  

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.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01989858
• Other study ID #: 2010-021052-25
• Status: Terminated
• Phase: Phase 3
• First received: June 16, 2011
• Last updated: January 28, 2015
• Start date: November 2010
• Est. completion date: December 2013

Study information

• Verified date: July 2010
• Source: Mario Negri Institute for Pharmacological Research
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ethics CommitteeItaly: The Italian Medicines Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1180
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Gastric Adenocarcinoma

Intervention

Other:
• peri-operative cht
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.
• post-operative CHT
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.
• peri-operative cht + post-operative cht-rtx
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: 5FU 200 mg/m² daily by continuous infusion via central line. 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: 5FU 225 mg/m² given as a continuous iv infusion or capecitabine 825 mg/m² bid given as a continuous oral administration during the entire course of RTX.
• post-operative cht + post-operative cht-rtx
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: 5FU 200 mg/m² daily by continuous infusion via central line. 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: 5FU 225 mg/m² given as a continuous iv infusion or capecitabine 825 mg/m² bid given as a continuous oral administration during the entire course of RTX.

Locations

Country	Name	City	State
Italy	Ospedali Riuniti di Bergamo	Bergamo	BG
Italy	A.O. Sant'Orsola Malpighi	Bologna	BO
Italy	Policlinico Sant'Orsola Malpighi	Bologna	BO
Italy	A. O. "Ospedale di Circolo di Busto Arsizio" - Busto Arsizio (VA)	Busto Arsizio	VA
Italy	IRCC/FPO -Istituto per la Ricerca e la Cura del Cancro di Candiolo	Candiolo	TO
Italy	Ospedale "Ramazzini " di Carpi	Carpi	MO
Italy	Azienda Ospedaliero-Universitaria "Policlinico-Vittorio Emanuele"	Catania	CT
Italy	Policlinico Universitario Mater Domini	Catanzaro	CZ
Italy	A.O. Santa Croce e Carle	Cuneo	CN
Italy	Ospedale Santa Croce Fano	Fano	PU
Italy	Azienda Ospedaliero- Universitaria Careggi - Firenze	Firenze	FI
Italy	A. O. "Carlo Poma"	Mantova	MN
Italy	Azienda Ospedaliera "San Paolo"	Milano	MI
Italy	Fondazione IRCCS Ospedale Maggiore Policlinico	Milano	MI
Italy	Istituto Nazionale per la Cura e lo Studio dei Tumori	Milano	MI
Italy	Istituto Oncologico Europeo	Milano	MI
Italy	A.O. Ospedale San Gerardo	Monza	MB
Italy	Fondazione "G. Pascale" Istituto Tumori di Napoli	Napoli
Italy	IRCCS Istituto Oncologico Veneto	Padova	PD
Italy	Ospedale "Guglielmo da Saliceto"	Piacenza	PC
Italy	Azienda Ospedaliera 'San Carlo'	Potenza	PZ
Italy	Ospedale Misericordia e Dolce - USL 4	Prato	PO
Italy	Arcispedale S. Maria Nuova Azienda Ospedaliera	Reggio Emilia	RE
Italy	Policlinico Universitario A. Gemelli	Roma	RM
Italy	Università "Campus Bio-Medico"	Roma	RM
Italy	Istituto Clinico Humanitas	Rozzano	MI
Italy	A. O. Busto Arsizio - P.O. Saronno	Saronno	VA
Italy	Casa di Cura MultiMedica	Sesto San Giovanni	MI
Italy	A.O. della Valtellina e della Valchiavenna - "Ospedale E. Morelli"	Sondalo	SO
Italy	A. O. Ospedale Treviglio-Caravaggio	Treviglio	BG
Italy	A.O. Ospedale di Circolo e Fondazione Macchi	Varese	VA
Italy	Azienda Ospedaliera di Desio e Vimercate	Vimercate	MB

Sponsors (1)

Lead Sponsor	Collaborator
Mario Negri Institute for Pharmacological Research

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival (OS)- Timing Study	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	No
Secondary	Dose-intensity	Dose-intensity, that is the dose of effective drug administrated per unit time (mg/m2/week or Gy/week); Dose and/or time modifications; Premature withdrawals	up to 8 weeks	No
Secondary	Maximum toxicity grade	Maximum toxicity grade experienced by each patient for each toxicity; Patients experiencing grade 3-4 toxicity for each toxicity; Type,frequency and nature of serious adverse events (SAEs); Patients with at least a SAE; Patients with at least a serious adverse drug reaction (SADR)	up to 8 weeks	Yes
Secondary	Disease Free Survival (DFS) - Timing Study	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	No
Secondary	Relapse Free Survival (l-RFS)- RTX Study	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	No