Clinical trial NCT02076594: Low-Tox Vs Eox In Patients With Locally Advanced Unresectable Or Metastatic Gastric Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Locally Advanced Unresectable Gastric Cancer
Metastatic Gastric Cancer
Lead sponsor: Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente
Sponsor class: OTHER
Collaborators: name: Regione Lombardia
First posted: 2014-03-03
Enrollment: 171
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: 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 outcomes:
measure: Overall Survival (OS)
timeFrame: Measured as the time from randomization to the date of death from any cause, assessed up to 18 months of follow up
measure: Objective Response Rate (CR + PR) according to RECIST 1.1 guideline
timeFrame: Measured as the time from randomization, assessed up to 18 months of follow up
measure: Disease control rate: CR + PR + SD lasting > 12 weeks
timeFrame: Measured as the time from randomization, assessed up to 18 months of follow up
measure: 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
timeFrame: Measured as the time from randomization, assessed up to 18 months of follow up
Other outcomes:
Locations:
city: Bari
country: Italy
facility: Istituto Tumori
state: BA
city: Bergamo
country: Italy
facility: Azienda Ospedaliera Papa Giovanni XXIII
state: BG
city: Treviglio
country: Italy
facility: A.O. Treviglio-Caravaggio
state: BG
city: Monserrato
country: Italy
facility: Azienda Ospedaliera Universitaria di Cagliari
state: CA
city: Como
country: Italy
facility: Azienda Ospedaliera Sant'Anna
state: CO
city: Lecco
country: Italy
facility: Ospedale di Circolo A. Manzoni
state: LC
city: Latina
country: Italy
facility: Ospedale Santa Maria Goretti Latina
state: LT
city: Camaiore
country: Italy
facility: A.O. Ospedale Versilia
state: LU
city: Taormina
country: Italy
facility: P.O. "San Vincenzo" Taormina
state: ME
city: Gorgonzola
country: Italy
facility: Osped. Di Circolo Serbelloni-Gorgonzola
state: MI
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
state: MI
city: Milano
country: Italy
facility: IRCCS Istituto Europeo di Oncologia (IEO)
state: MI
city: Milano
country: Italy
facility: Azienda Ospedaliera San Paolo
state: MI
city: Milano
country: Italy
facility: Ospedale L. Sacco
state: MI
city: Carpi
country: Italy
facility: Ospedale di Carpi
state: MO
city: Piacenza
country: Italy
facility: AUSL di Piacenza
state: PC
city: Pesaro
country: Italy
facility: A.O. Ospedali Riuniti Marche Nord - Presidio S. Salvatore Muraglia
state: PE
city: Pescara
country: Italy
facility: A. O. di Pescara - Ospedale Civile Spirito Santo
state: PE
city: Prato
country: Italy
facility: Ospedale Misericordia e Dolce
state: PO
city: Potenza
country: Italy
facility: Azienda Ospedaliera Ospedale San Carlo
state: PZ
city: Reggio Emilia
country: Italy
facility: Ospedale di S. Maria Nuova
state: RE
city: Roma
country: Italy
facility: Ospedale Fatebenefratelli
state: RM
city: Varese
country: Italy
facility: Ospedale di Circolo e Fondazione Macchi di Varese
state: VA
city: Negrar
country: Italy
facility: Ospedale Sacro Cuore Don Calabria di Negrar
state: VR
city: Napoli
country: Italy
facility: IRCCS Istituto Nazionale Tumori Fondazione Pascale
Study officials:
affiliation: A.O. Papa Giovanni XXIII di Bergamo, Oncologia Medica
name: Roberto Labianca, MD
role: STUDY_DIRECTOR
affiliation: Policlinico Umbero I di Roma, UOC Oncologia Medica B
name: Enrico Cortesi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ospedale Fatebenefratelli di Roma, Oncologia
name: Domenico Cristiano Corsi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ospedale degli Infermi di Biella, Oncologia
name: Pietro Sozzi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: AUSL di Piacenza, Oncologia Medica
name: Luigi Cavanna, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: A.O. Ospedale San Carlo di Potenza, Oncologia Medica
name: Domenico Bilancia, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: ASUR Zona 6 di Fabriano, Oncologia
name: Rosa Rita Silva, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: IRCCS Istituto Europeo di Oncologia di Milano, Tumori digestivi superiori e Neuroendocrini
name: Nicola Fazio, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: A. O. Sant'Anna di Como, Oncologia
name: Monica Giordano, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ospedale Civile di Sondrio, Oncologia Medica
name: Alessandro Bertolini, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: A.O. Ospedale Maggiore di Lodi, Oncologia
name: Giovanni Ucci, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: A.O. di Pescara - Oncologia
name: Donato Natale, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: A.O. San Paolo di Milano, Oncologia Medica
name: Daris Ferrari, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ospedale di Circolo e Fondazione Macchi di Varese, Oncologia
name: Graziella Pinotti, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ospedale di S. Maria Nuova di Reggio Emilia, Oncologia Medica
name: Ermanno Rondini, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ospedale Sacro Cuore Don Calabria di Negrar, Oncologia Medica
name: Massimo Cirillo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: IRCCS Istituto Nazionale Tumori Fondazione Pascale di Napoli, Oncologia Medica Addominale
name: Rosario Vincenzo Iaffaioli, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ospedale Misericordia e Dolce di Prato, Oncologia Medica
name: Andrea Ciarlo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ospedale L. Sacco di Milano, Oncologia
name: Elena Piazza, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Azienda Ospedaliera Città della Salute e della Scienza di Torino, Oncologia Medica
name: Libero Ciuffreda, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ospedale di Circolo A. Manzoni di Lecco, Oncologia Medica
name: Stefania Dell'Oro, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ospedale di Carpi, Medicina Oncologica
name: Fabrizio Artioli, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ospedale Generale Provinciale di Saronno, Oncologia Medica
name: Claudio Verusio, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: A.O. Ospedali Riuniti Marche Nord - Presidio S. Salvatore Muraglia, Oncologia
name: Vincenzo Catalano, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: ASDAA Bolzano, Oncologia Medica
name: Claudio Graiff, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: A.O. Ospedale Versilia di Camaiore, Oncologia Medica
name: Domenico Amoroso, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Medicina Oncologica 1
name: Maria Di Bartolomeo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Istituto Tumori di Bari, Oncologia Medica
name: Nicola Silvestris, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: OSPED. DI CIRCOLO SERBELLONI-GORGONZOLA - GORGONZOLA (MI)
name: Maria C. Zavettieri, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: OSPEDALE SANTA MARIA GORETTI LATINA
name: Enzo Veltri, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: P.O. "SAN VINCENZO" TAORMINA - TAORMINA (ME)
name: Francesco Ferraù, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: OSPEDALE POLICLINICO G.B. ROSSI (BORGO ROMA) DI VERONA
name: Giampaolo Tortora, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: A.O. TREVIGLIO-CARAVAGGIO - TREVIGLIO (BG)
name: Sandro Barni, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: A.O.U. di Cagliari - Presidio di Monserrato
name: Mario Scartozzi, MD
role: PRINCIPAL_INVESTIGATOR
References: