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

Primary Purpose

Locally Advanced Unresectable Gastric Cancer, Metastatic Gastric Cancer

Status

Terminated

Phase

Phase 3

Locations

Italy

Study Type

Interventional

Intervention

Docetaxel

Epirubicin

Oxaliplatin

Capecitabine

About this trial

This is an interventional treatment trial for Locally Advanced Unresectable Gastric Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

Istituto Tumori
Azienda Ospedaliera Papa Giovanni XXIII
A.O. Treviglio-Caravaggio
Azienda Ospedaliera Universitaria di Cagliari
Azienda Ospedaliera Sant'Anna
Ospedale di Circolo A. Manzoni
Ospedale Santa Maria Goretti Latina
A.O. Ospedale Versilia
P.O. "San Vincenzo" Taormina
Osped. Di Circolo Serbelloni-Gorgonzola
Fondazione IRCCS Istituto Nazionale dei Tumori
IRCCS Istituto Europeo di Oncologia (IEO)
Azienda Ospedaliera San Paolo
Ospedale L. Sacco
Ospedale di Carpi
AUSL di Piacenza
A.O. Ospedali Riuniti Marche Nord - Presidio S. Salvatore Muraglia
A. O. di Pescara - Ospedale Civile Spirito Santo
Ospedale Misericordia e Dolce
Azienda Ospedaliera Ospedale San Carlo
Ospedale di S. Maria Nuova
Ospedale Fatebenefratelli
Ospedale di Circolo e Fondazione Macchi di Varese
Ospedale Sacro Cuore Don Calabria di Negrar
IRCCS Istituto Nazionale Tumori Fondazione Pascale

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Docetaxel & Oxaliplatin & Capecitabine

Epirubicin & Oxaliplatin & Capecitabine

Arm Description

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)

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)

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

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)

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)

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)

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)

Full Information

NCT ID

NCT02076594

First Posted

August 20, 2013

Last Updated

October 7, 2019

Sponsor

Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente

Collaborators

Regione Lombardia

1. Study Identification

Unique Protocol Identification Number

NCT02076594

Brief Title

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

2. Study Status

Record Verification Date

January 2019

Overall Recruitment Status

Terminated

Why Stopped

The interim analysis performed on 09 November 2018, showed the failure to achieve the primary objective of effectiveness of the experimental treatment.

Study Start Date

January 2013 (undefined)

Primary Completion Date

December 2018 (Actual)

Study Completion Date

December 31, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente

Collaborators

Regione Lombardia

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Locally Advanced Unresectable Gastric Cancer, Metastatic Gastric Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

171 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Docetaxel & Oxaliplatin & Capecitabine

Arm Type

Experimental

Arm Description

Arm Title

Epirubicin & Oxaliplatin & Capecitabine

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Docetaxel

Other Intervention Name(s)

Taxotere 20 mg/mL

Intervention Description

Powder for solution for infusion

Intervention Type

Drug

Intervention Name(s)

Epirubicin

Other Intervention Name(s)

Farmorubicina 2mg/mL

Intervention Description

Solution for infusion

Intervention Type

Drug

Intervention Name(s)

Oxaliplatin

Other Intervention Name(s)

Eloxatin 5 mg/mL

Intervention Description

Powder for solution for infusion

Intervention Type

Drug

Intervention Name(s)

Capecitabine

Other Intervention Name(s)

Xeloda 150 mg, Xeloda 500 mg

Intervention Description

Film coated tablets

Primary Outcome Measure Information:

Title

Progression Free Survival (PFS)

Description

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

Secondary Outcome Measure Information:

Title

Overall Survival (OS)

Description

Time Frame

Measured as the time from randomization to the date of death from any cause, assessed up to 18 months of follow up

Title

Objective Response Rate (CR + PR) according to RECIST 1.1 guideline

Description

Time Frame

Measured as the time from randomization, assessed up to 18 months of follow up

Title

Disease control rate: CR + PR + SD lasting > 12 weeks

Description

Time Frame

Measured as the time from randomization, assessed up to 18 months of follow up

Title

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

Description

Time Frame

Measured as the time from randomization, assessed up to 18 months of follow up

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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)

Overall Study Officials: