Low-Tox Vs Eox In Patients With Locally Advanced Unresectable Or Metastatic Gastric Cancer

A Randomized Phase III Study Of Low-Docetaxel Oxaliplatin, Capecitabine (Low-Tox) Vs Epirubicin, Oxaliplatin And Capecitabine (Eox) In Patients With Locally Advanced Unresectable Or Metastatic Gastric Cancer

This is a randomized, parallel group, non-blinded phase III trial. Patients with advanced (locoregional or metastatic) gastric cancer not previously treated with chemotherapy for this stage will be randomized in a 1:1 ratio to receive low-TOX (arm A) or EOX (arm B). Randomization will be stratified by performance status (ECOG 0, 1 and 2).

Study Overview

• Status: Terminated
• Conditions: Metastatic Gastric Cancer; Locally Advanced Unresectable Gastric Cancer
• Intervention / Treatment: Drug: Docetaxel; Drug: Oxaliplatin; Drug: Capecitabine; Drug: Epirubicin

Detailed Description

Although the incidence of the adenocarcinoma of the stomach is slowly decreasing, gastric cancer represents the second worldwide cause of cancer death after lung cancer. In patients with advanced disease, chemotherapy improves survival and quality of life. Combinations of two or three drugs including a platin derivative (cisplatin or oxaliplatin), a fluoropyrimidine (5FU or capecitabine) and an anthracycline (usually epirubicin) have demonstrated superiority compared to single or double agent therapy and are the current standard. As of today there are no published studies comparing anthracycline-based to taxane-based three-drug regimens. The objective of the present study is to compare EOX as evaluated in REAL-2 to the low-TOX regimen consisting of docetaxel, oxaliplatin and capecitabine. Low-TOX is expected to be better tolerated than the original DCF regimen. The study will be performed in the HER2 negative patients.

• Study Type: Interventional
• Enrollment (Actual): 171
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Napoli, Italy, 80131
    • IRCCS Istituto Nazionale Tumori Fondazione Pascale
  • BA
    • Bari, BA, Italy, 70124
      • Istituto Tumori
  • BG
    • Bergamo, BG, Italy, 24127
      • Azienda Ospedaliera Papa Giovanni XXIII
    • Treviglio, BG, Italy, 24047
      • A.O. Treviglio-Caravaggio
  • CA
    • Monserrato, CA, Italy, 09042
      • Azienda Ospedaliera Universitaria di Cagliari
  • CO
    • Como, CO, Italy, 22020
      • Azienda Ospedaliera Sant'Anna
  • LC
    • Lecco, LC, Italy, 23900
      • Ospedale di Circolo A. Manzoni
  • LT
    • Latina, LT, Italy, 04100
      • Ospedale Santa Maria Goretti Latina
  • LU
    • Camaiore, LU, Italy, 55041
      • A.O. Ospedale Versilia
  • ME
    • Taormina, ME, Italy, 98039
      • P.O. "San Vincenzo" Taormina
  • MI
    • Gorgonzola, MI, Italy, 20064
      • Osped. Di Circolo Serbelloni-Gorgonzola
    • Milano, MI, Italy, 20133
      • Fondazione IRCCS Istituto Nazionale dei Tumori
    • Milano, MI, Italy, 20142
      • Azienda Ospedaliera San Paolo
    • Milano, MI, Italy, 20157
      • Ospedale L. Sacco
    • Milano, MI, Italy, 20141
      • IRCCS Istituto Europeo di Oncologia (IEO)
  • MO
    • Carpi, MO, Italy, 41012
      • Ospedale di Carpi
  • PC
    • Piacenza, PC, Italy, 29100
      • AUSL di Piacenza
  • PE
    • Pesaro, PE, Italy, 61122
      • A.O. Ospedali Riuniti Marche Nord - Presidio S. Salvatore Muraglia
    • Pescara, PE, Italy, 65124
      • A. O. di Pescara - Ospedale Civile Spirito Santo
  • PO
    • Prato, PO, Italy, 59100
      • Ospedale Misericordia e Dolce
  • PZ
    • Potenza, PZ, Italy, 85100
      • Azienda Ospedaliera Ospedale San Carlo
  • RE
    • Reggio Emilia, RE, Italy, 42100
      • Ospedale di S. Maria Nuova
  • RM
    • Roma, RM, Italy, 00186
      • Ospedale Fatebenefratelli
  • VA
    • Varese, VA, Italy, 21100
      • Ospedale di Circolo e Fondazione Macchi di Varese
  • VR
    • Negrar, VR, Italy, 37024
      • Ospedale Sacro Cuore Don Calabria di Negrar

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signed written informed consent prior to beginning protocol specific procedures
• Male or female > 18 years of age
• Histologically proven diagnosis of adenocarcinoma of the stomach
• HER2 negative tumor or HER2+ tumors not qualifying for herceptin therapy
• Locally advanced (non resectable) or metastatic gastric cancer
• Presence of measurable disease with at least one measurable lesion by means of CT scan or MRI in not previously irradiated area(s) (according to RECIST criteria (version 1.1)
• Life expectancy of >/= 3 months
• ECOG performance status of 0-2 at study entry
• Neutrophils >/= 2.0 x 1000000000/L, platelets >/= 100 x 1000000000/L, and hemoglobin >/= 10 g/dL
• Bilirubin level either normal or </= 1.5 x ULN
• AST and ALT </= 2.5 X UNL (</= 5 x ULN if liver metastasis are present
• Alkaline phosphatase (ALP) </= 2.5 X ULN; patients with alkaline phosphatase > 2.5x ULN and AST and ALT </= 1.5 x ULN are equally eligible
• Serum creatinine < 1.5 x ULN. In presence border-line values, the calculated creatinine clearance should be >/= 60 mL/min
• Negative pregnancy test (if female in reproductive years)
• Effective contraception prior to study entry and for the duration of the study participation, for both male and female patients of child producing potential
• Able and willing to comply with scheduled visits, therapy plans and laboratory tests required in this protocol

Exclusion Criteria:

• Previous chemotherapy, except adjuvant treatment administered at least 1 year before study entry
• Concurrent chronic systemic immune therapy
• Any investigational agent(s) 4 weeks prior to entry
• Clinically relevant coronary artery disease or a history of a myocardial infarction or a history of hypertension not controlled by therapy within the last 12 months
• Known hypersensitivity to study drugs. Known grade 3 or 4 allergic reaction to any of the components of the treatment
• Known drug abuse/ alcohol abuse
• Acute or subacute intestinal occlusion and any other significant chronic gastrointestinal disease that might interfere with absorption of oral treatment
• History of clinically relevant psychiatric disability precluding informed consent
• Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
• Pregnant or breastfeeding women
• Active uncontrolled infection(s)
• Positive for HIV serology and/or viral hepatitis B or C
• Any concurrent malignancy other than non-melanoma skin cancer, or carcinoma in situ of the cervix. (Patients with a previous malignancy but without evidence of disease for ≥ 5 years will be allowed to enter the trial)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Docetaxel & Oxaliplatin & Capecitabine; Patients will receive cycles every 3 weeks of Docetaxel (35 mg/ m2, intravenous at days 1 and 8 by 1-hour infusion)and Oxaliplatin (80 mg/ m2, intravenous at day 1 by 2-hour infusion) and Capecitabine (750 mg/ m2, oral tablets of 500 and 150 mg, x2 daily for 2 weeks)	Drug: Docetaxel; Powder for solution for infusion; Other Names: Taxotere 20 mg/mL; Drug: Oxaliplatin; Powder for solution for infusion; Other Names: Eloxatin 5 mg/mL; Drug: Capecitabine; Film coated tablets; Other Names: Xeloda 150 mg; Xeloda 500 mg
Experimental: Epirubicin & Oxaliplatin & Capecitabine; Patients will receive cycles every 3 weeks of Epirubicin (50 mg/ m2, intravenous on day 1 by 2-hour infusion)and Oxaliplatin (130 mg/ m2, intravenous on day 1 by 2-hour infusion) and Capecitabine (625 mg/ m2,oral tablets of 500 and 150 mg, x2 daily for 3 weeks)	Drug: Oxaliplatin; Powder for solution for infusion; Other Names: Eloxatin 5 mg/mL; Drug: Capecitabine; Film coated tablets; Other Names: Xeloda 150 mg; Xeloda 500 mg; Drug: Epirubicin; Solution for infusion; Other Names: Farmorubicina 2mg/mL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	To determine the progression free survival (PFS) of patients with locally advanced unresectable or metastatic gastric cancer treated with Docetaxel plus Oxaliplatin plus Capecitabine (Arm A) or with Epirubicin plus Oxaliplatin plus Capecitabine (Arm B)	Measured as the time from randomization to the date of local or regional progression, distant metastasis, second primary malignancy or death, assessed up to 18 months of follow up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	To assess overall survival (OS) of patients with locally advanced unresectable or metastatic gastric cancer treated with Docetaxel plus Oxaliplatin plus Capecitabine (Arm A) or with Epirubicin plus Oxaliplatin plus Capecitabine (Arm B)	Measured as the time from randomization to the date of death from any cause, assessed up to 18 months of follow up
Objective Response Rate (CR + PR) according to RECIST 1.1 guideline	To assess objective response rate (CR+PR)of patients with locally advanced unresectable or metastatic gastric cancer treated with Docetaxel plus Oxaliplatin plus Capecitabine (Arm A) or with Epirubicin plus Oxaliplatin plus Capecitabine (Arm B)	Measured as the time from randomization, assessed up to 18 months of follow up
Disease control rate: CR + PR + SD lasting > 12 weeks	To assess disease control rate of patients with locally advanced unresectable or metastatic gastric cancer treated with Docetaxel plus Oxaliplatin plus Capecitabine (Arm A) or with Epirubicin plus Oxaliplatin plus Capecitabine (Arm B)	Measured as the time from randomization, assessed up to 18 months of follow up
Tolerability of the treatments evaluated in term of occurrence of: side effects graded according to the NCI-CTCAE scale (version 4.0); serious adverse reactions, expected and unexpected	To assess tolerability of the treatments of patients with locally advanced unresectable or metastatic gastric cancer treated with Docetaxel plus Oxaliplatin plus Capecitabine (Arm A) or with Epirubicin plus Oxaliplatin plus Capecitabine (Arm B)	Measured as the time from randomization, assessed up to 18 months of follow up

Collaborators and Investigators

• Sponsor: Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente
• Collaborators: Regione Lombardia
• Investigators: Study Director: Roberto Labianca, MD, A.O. Papa Giovanni XXIII di Bergamo, Oncologia Medica; Principal Investigator: Enrico Cortesi, MD, Policlinico Umbero I di Roma, UOC Oncologia Medica B; Principal Investigator: Domenico Cristiano Corsi, MD, Ospedale Fatebenefratelli di Roma, Oncologia; Principal Investigator: Pietro Sozzi, MD, Ospedale degli Infermi di Biella, Oncologia; Principal Investigator: Luigi Cavanna, MD, AUSL di Piacenza, Oncologia Medica; Principal Investigator: Domenico Bilancia, MD, A.O. Ospedale San Carlo di Potenza, Oncologia Medica; Principal Investigator: Rosa Rita Silva, MD, ASUR Zona 6 di Fabriano, Oncologia; Principal Investigator: Nicola Fazio, MD, IRCCS Istituto Europeo di Oncologia di Milano, Tumori digestivi superiori e Neuroendocrini; Principal Investigator: Monica Giordano, MD, A. O. Sant'Anna di Como, Oncologia; Principal Investigator: Alessandro Bertolini, MD, Ospedale Civile di Sondrio, Oncologia Medica; Principal Investigator: Giovanni Ucci, MD, A.O. Ospedale Maggiore di Lodi, Oncologia; Principal Investigator: Donato Natale, MD, A.O. di Pescara - Oncologia; Principal Investigator: Daris Ferrari, MD, A.O. San Paolo di Milano, Oncologia Medica; Principal Investigator: Graziella Pinotti, MD, Ospedale di Circolo e Fondazione Macchi di Varese, Oncologia; Principal Investigator: Ermanno Rondini, MD, Ospedale di S. Maria Nuova di Reggio Emilia, Oncologia Medica; Principal Investigator: Massimo Cirillo, MD, Ospedale Sacro Cuore Don Calabria di Negrar, Oncologia Medica; Principal Investigator: Rosario Vincenzo Iaffaioli, MD, IRCCS Istituto Nazionale Tumori Fondazione Pascale di Napoli, Oncologia Medica Addominale; Principal Investigator: Andrea Ciarlo, MD, Ospedale Misericordia e Dolce di Prato, Oncologia Medica; Principal Investigator: Elena Piazza, MD, Ospedale L. Sacco di Milano, Oncologia; Principal Investigator: Libero Ciuffreda, MD, Azienda Ospedaliera Città della Salute e della Scienza di Torino, Oncologia Medica; Principal Investigator: Stefania Dell'Oro, MD, Ospedale di Circolo A. Manzoni di Lecco, Oncologia Medica; Principal Investigator: Fabrizio Artioli, MD, Ospedale di Carpi, Medicina Oncologica; Principal Investigator: Claudio Verusio, MD, Ospedale Generale Provinciale di Saronno, Oncologia Medica; Principal Investigator: Vincenzo Catalano, MD, A.O. Ospedali Riuniti Marche Nord - Presidio S. Salvatore Muraglia, Oncologia; Principal Investigator: Claudio Graiff, MD, ASDAA Bolzano, Oncologia Medica; Principal Investigator: Domenico Amoroso, MD, A.O. Ospedale Versilia di Camaiore, Oncologia Medica; Principal Investigator: Maria Di Bartolomeo, MD, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Medicina Oncologica 1; Principal Investigator: Nicola Silvestris, MD, Istituto Tumori di Bari, Oncologia Medica; Principal Investigator: Maria C. Zavettieri, MD, OSPED. DI CIRCOLO SERBELLONI-GORGONZOLA - GORGONZOLA (MI); Principal Investigator: Enzo Veltri, MD, Ospedale Santa Maria Goretti Latina; Principal Investigator: Francesco Ferraù, MD, P.O. "SAN VINCENZO" TAORMINA - TAORMINA (ME); Principal Investigator: Giampaolo Tortora, MD, Ospedale Policlinico G.B. Rossi (Borgo Roma) di Verona; Principal Investigator: Sandro Barni, MD, A.O. TREVIGLIO-CARAVAGGIO - TREVIGLIO (BG); Principal Investigator: Mario Scartozzi, MD, A.O.U. di Cagliari - Presidio di Monserrato

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Actual): December 1, 2018
• Study Completion (Actual): December 31, 2018

Study Registration Dates

• First Submitted: August 20, 2013
• First Submitted That Met QC Criteria: February 26, 2014
• First Posted (Estimate): March 3, 2014

Study Record Updates

• Last Update Posted (Actual): October 9, 2019
• Last Update Submitted That Met QC Criteria: October 7, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Docetaxel; Capecitabine; Epirubicin; Oxaliplatin
• Other Study ID Numbers: LEGA; 2011-005537-39 (EudraCT Number)