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

Metastatic Gastric Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02076594
• Other study ID #: LEGA
• Secondary ID: 2011-005537-39
• Status: Terminated
• Phase: Phase 3
• Start date: January 2013
• Est. completion date: December 31, 2018

Study information

• Verified date: January 2019
• Source: Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 171
• Est. completion date: December 31, 2018
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Locally Advanced Unresectable Gastric Cancer
• Metastatic Gastric Cancer
• Stomach Neoplasms

Intervention

Drug:
• Docetaxel
Powder for solution for infusion
• Epirubicin
Solution for infusion
• Oxaliplatin
Powder for solution for infusion
• Capecitabine
Film coated tablets

Locations

Country	Name	City	State
Italy	Istituto Tumori	Bari	BA
Italy	Azienda Ospedaliera Papa Giovanni XXIII	Bergamo	BG
Italy	A.O. Ospedale Versilia	Camaiore	LU
Italy	Ospedale di Carpi	Carpi	MO
Italy	Azienda Ospedaliera Sant'Anna	Como	CO
Italy	Osped. Di Circolo Serbelloni-Gorgonzola	Gorgonzola	MI
Italy	Ospedale Santa Maria Goretti Latina	Latina	LT
Italy	Ospedale di Circolo A. Manzoni	Lecco	LC
Italy	Azienda Ospedaliera San Paolo	Milano	MI
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano	MI
Italy	IRCCS Istituto Europeo di Oncologia (IEO)	Milano	MI
Italy	Ospedale L. Sacco	Milano	MI
Italy	Azienda Ospedaliera Universitaria di Cagliari	Monserrato	CA
Italy	IRCCS Istituto Nazionale Tumori Fondazione Pascale	Napoli
Italy	Ospedale Sacro Cuore Don Calabria di Negrar	Negrar	VR
Italy	A.O. Ospedali Riuniti Marche Nord - Presidio S. Salvatore Muraglia	Pesaro	PE
Italy	A. O. di Pescara - Ospedale Civile Spirito Santo	Pescara	PE
Italy	AUSL di Piacenza	Piacenza	PC
Italy	Azienda Ospedaliera Ospedale San Carlo	Potenza	PZ
Italy	Ospedale Misericordia e Dolce	Prato	PO
Italy	Ospedale di S. Maria Nuova	Reggio Emilia	RE
Italy	Ospedale Fatebenefratelli	Roma	RM
Italy	P.O. "San Vincenzo" Taormina	Taormina	ME
Italy	A.O. Treviglio-Caravaggio	Treviglio	BG
Italy	Ospedale di Circolo e Fondazione Macchi di Varese	Varese	VA

Sponsors (2)

Lead Sponsor	Collaborator
Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente	Regione Lombardia

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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