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

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

Interventions

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.

OTHER

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.

OTHER

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.

OTHER

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.

Sponsors & Collaborators

• Mario Negri Institute for Pharmacological Research

  lead OTHER

Principal Investigators

• Francesco Di Costanzo, MD · Azienda Ospedaliero- Universitaria Careggi - Firenze U.O. Medica

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

FACTORIAL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2010-11-30

Primary Completion

2013-12-31

Completion

2013-12-31

Countries

• Italy

Study Locations