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

NCT01989858 | Terminated Phase 3 DMC

• 1 other identifier: 2010-021052-25
• Study Type: interventional
• Target: 1,180
• Locations: 1 country
• Sites: 32

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.

Conditions

Gastric Adenocarcinoma

Keywords

localized gastric adenocarcinoma, operable considered.

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (4)

• Dose-intensity

  up to 8 weeks

• Maximum toxicity grade

  up to 8 weeks

• Disease Free Survival (DFS) - Timing Study

  3 years

• Relapse Free Survival (l-RFS)- RTX Study

  3 years

Study Arms (4)

peri-operative CHT (Arm A)

EXPERIMENTAL

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.

Other: peri-operative cht

post-operative CHT (Arm B)

ACTIVE COMPARATOR

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).

Other: post-operative CHT

peri-operative CHT + post-operative CHT-RTX (Arm C)

EXPERIMENTAL

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.

Other: peri-operative cht + post-operative cht-rtx

post-operative CHT + post-operative CHT-RTX (Arm D)

ACTIVE COMPARATOR

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).

Other: post-operative cht + post-operative cht-rtx

Interventions

peri-operative cht OTHER

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.

peri-operative CHT (Arm A)

post-operative CHT OTHER

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.

post-operative CHT (Arm B)

peri-operative cht + post-operative cht-rtx OTHER

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.

peri-operative CHT + post-operative CHT-RTX (Arm C)

post-operative cht + post-operative cht-rtx OTHER

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 (Arm D)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Mario Negri Institute for Pharmacological Research: lead

Study Sites (32)

Ospedali Riuniti di Bergamo

Bergamo, BG, 24128, Italy

Location

A. O. Ospedale Treviglio-Caravaggio

Treviglio, BG, 24047, Italy

Location

A.O. Sant'Orsola Malpighi

Bologna, BO, 40138, Italy

Location

Policlinico Sant'Orsola Malpighi

Bologna, BO, 40138, Italy

Location

A.O. Santa Croce e Carle

Cuneo, CN, 12100, Italy

Location

Azienda Ospedaliero-Universitaria "Policlinico-Vittorio Emanuele"

Catania, CT, 95123, Italy

Location

Policlinico Universitario Mater Domini

Catanzaro, CZ, 88100, Italy

Location

Azienda Ospedaliero- Universitaria Careggi - Firenze

Florence, FI, 50141, Italy

Location

A.O. Ospedale San Gerardo

Monza, MB, 20052, Italy

Location

Azienda Ospedaliera di Desio e Vimercate

Vimercate, MB, 20059, Italy

Location

Fondazione IRCCS Ospedale Maggiore Policlinico

Milan, MI, 20122, Italy

Location

Istituto Nazionale per la Cura e lo Studio dei Tumori

Milan, MI, 20133, Italy

Location

Istituto Oncologico Europeo

Milan, MI, 20141, Italy

Location

Azienda Ospedaliera "San Paolo"

Milan, MI, 20142, Italy

Location

Istituto Clinico Humanitas

Rozzano, MI, 20089, Italy

Location

Casa di Cura MultiMedica

Sesto San Giovanni, MI, 20099, Italy

Location

A. O. "Carlo Poma"

Mantova, MN, 46100, Italy

Location

Ospedale "Ramazzini " di Carpi

Carpi, MO, 41012, Italy

Location

Ospedale "Guglielmo da Saliceto"

Piacenza, PC, 29100, Italy

Location

IRCCS Istituto Oncologico Veneto

Padua, PD, 35128, Italy

Location

Ospedale Misericordia e Dolce - USL 4

Prato, PO, 59100, Italy

Location

Ospedale Santa Croce Fano

Fano, PU, 61032, Italy

Location

Azienda Ospedaliera 'San Carlo'

Potenza, PZ, 85100, Italy

Location

Arcispedale S. Maria Nuova Azienda Ospedaliera

Reggio Emilia, RE, 42100, Italy

Location

Università "Campus Bio-Medico"

Roma, RM, 00128, Italy

Location

Policlinico Universitario A. Gemelli

Roma, RM, 00168, Italy

Location

A.O. della Valtellina e della Valchiavenna - "Ospedale E. Morelli"

Sondalo, SO, 23100, Italy

Location

IRCC/FPO -Istituto per la Ricerca e la Cura del Cancro di Candiolo

Candiolo, TO, 10060, Italy

Location

A. O. "Ospedale di Circolo di Busto Arsizio" - Busto Arsizio (VA)

Busto Arsizio, VA, 21052, Italy

Location

A. O. Busto Arsizio - P.O. Saronno

Saronno, VA, 21047, Italy

Location

A.O. Ospedale di Circolo e Fondazione Macchi

Varese, VA, 21100, Italy

Location

Fondazione "G. Pascale" Istituto Tumori di Napoli

Napoli, 80131, Italy

Location

Study Officials

• Francesco Di Costanzo, MD

  Azienda Ospedaliero- Universitaria Careggi - Firenze U.O. Medica

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2011
• First Posted: November 21, 2013
• Study Start: November 1, 2010
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: January 29, 2015

Record last verified: 2010-07

Locations

IT (32)