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).

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.

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)