Trial of Docetaxel, Oxaliplatin and Capecitabine (TEX) in Advanced or Metastatic Gastric Cancer

Inclusion criteria

• Written informed consent
• Histologically proven irresectable, metastatic or recurrent adenocarcinoma of the stomach or the gastroesophageal junction, i.e., Tx-4 M1 or T4 M0
• Irresectable (as judged by an experienced surgeon):

• T4 infiltrating of several organs
• T4 infiltrating one organ, but irresectable
• T4 infiltrating one organ, respectable, but inoperable patient
• The nodal status is neglected
• Measurable disease according to RECIST
• ECOG Performance Status ≤ 2
• Male or female patients aged ≥ 18 years
• Life expectancy ≥ 3 months
• Adequate bone marrow, hepatic and renal function:

• Haemoglobin > 9.0 g/dL (transfusions allowed to achieve or maintain levels)
• Absolute neutrophil count > 1.5 x 10^9/L
• Platelet count > 100 x 10^9/L
• ALAT, ASAT < 3.5 x ULN
• Alkaline phosphatase < 6 x ULN
• Total bilirubin < 1.0 x ULN
• Creatinine clearance > 50 mL/min (calculated according to Cockroft and Gault)
• Prior surgery must be more than 28 days ago
• Positive nodes as diagnosed on endorectal ultrasound and/or MRI (tumour is staged by preferably a high resolution MRI; if MRI is not available, locoregional staging must be performed by computed tomography plus endorectal ultrasound)
• Tumor staging must be done within 28 days from the start of the treatment
• Negative pregnancy test in women with childbearing of potential (within 7 days prior to the start of the chemotherapy)

• Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential

Exclusion criteria

• Prior cytotoxic chemotherapy or radiotherapy (a neoadjuvant or adjuvant chemotherapy must be completed and without progression for at least 6 months)
• Previous (within the last 5 years) or concurrent malignancies, with the exception of adequately treated in situ carcinoma of the cervix or basal cell carcinoma of the skin
• Peripheral neuropathy ≥ grade 2 (according to NCI CTCAE v 3.0)
• Patient must not have been treated with any investigational drug, agent nor procedure, (i.e., did not participate in another trial within 30 days) before entry in this trial
• Known allergy or any other adverse reaction to any of the study drugs or to any related compound
• Requirement for concurrent use of the antiviral agent sorivudine (antiviral) or chemically related analogues, such as brivudine
• Clinically significant concomitant diseases, such as:

• Active infection necessitating systemic antibiotics
• Interstitial lung diseases
• Chronic diarrhea, inflammatory bowel disease
• Neurological or psychiatric disease, dementia, epilepsy or untreated brain metastases
• Cardiac disease (e.g., congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmia not well controlled with medication) or myocardial infarction or resuscitation within the last 6 months
• Pregnant or lactating women are excluded
• Presence of adequate contraception in fertile patients (methods of adequate contraception are: intra-uterine device, hormonal contraception, vasectomy, tubal ligation or abstinence)
• Alcohol or drug abuse
• Ability to swallow tablets
• Psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule