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

October 7, 2019 updated by: Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente

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

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
171

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Progression Free Survival (PFS)
Time Frame: 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
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: Measured as the time from randomization to the date of death from any cause, assessed up to 18 months of follow up
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
Time Frame: Measured as the time from randomization, assessed up to 18 months of follow up
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
Time Frame: Measured as the time from randomization, assessed up to 18 months of follow up
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
Time Frame: Measured as the time from randomization, assessed up to 18 months of follow up
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

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Regione Lombardia

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 20, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 26, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 3, 2014

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 9, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 7, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • LEGA
  • 2011-005537-39 (EudraCT Number)

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.

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