That panitumumab in combination with Epirubicin, Cisplatin and Capecitabine (ECX) will safely decrease the frequency of pT3/T4 below that of ECX alone in subjects with locally advanced adenocarcinoma of the stomach and gastroesophageal junction.

Inclusion Criteria:

• Competent to comprehend, sign, and date an IEC-approved informed consent form, written informed consent.
• Of either gender and aged 18 years or more.
• Diagnosed with histologically confirmed adenocarcinoma of the stomach or the gastroesophageal junction of Type I/II/III according to the classification of Siewert et al, 1996.
• Stage uT/3 or 4 N0/+ and M0 disease evaluated by endoscopic ultrasound, spiral computed tomography of the chest, abdomen and pelvis and by laparoscopy in uT3/T4 tumors.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Leucocyte count > 3,000/mm3.
• Platelet count ≥100,000/mm3.
• Haemoglobin ≥10 g/dl.
• Serum creatinine ≤ 1.5x of upper limit of normal (ULN).
• Creatinine clearance > 60 ml/kg/min measured either by 24-h urine sampling or calculated by using the Cockcroft-Gault formula .
• Aspartate aminotransferase (AST) ≤3 x ULN.
• Alanine aminotransferase (ALT) ≤3 x ULN.
• Bilirubin ≤ 1.5 x ULN.
• Magnesium ≥ lower limit of normal.
• Calcium ≥ lower limit of normal.
• Subject is deemed a good candidate for surgery.

Exclusion Criteria:

• Any metastatic disease.
• Other malignant tumours less than five years old. Exceptions include basocellular carcinoma, in situ cancer of the cervix of the uterus, or any curatively-treated other malignancies without evidence of disease for more than five years.
• Significant ascites or pleural effusion.
• Prior anti-EGFr antibody therapy (e.g. cetuximab) or treatment with small molecule EGFr tyrosine kinase inhibitors (e.g. erlotinib).
• Prior chemotherapy, radiotherapy or antibody therapy for gastric cancer or cancer of the gastro-oesophageal junction.
• Concomitant therapy with sorivudine or analogue compounds.
• Known previous or ongoing abuse of narcotic drug, other medication or alcohol.
• Significant cardiovascular disease including New York Heart Association (NYHA) grade II or greater congestive heart failure, peripheral arterial occlusive disease stage II or greater, symptomatic coronary heart disease, insufficiently treated arterial hypertension, unstable angina or myocardial infarction within 12 months before initiating study treatment or a history of ventricular arrhythmia.
• History or evidence upon physical examination of CNS disease unless adequately treated, seizure not controlled with standard medical therapy, or history of stroke.
• History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis on baseline chest CT scan.
• Pre-existing polyneuropathy grade >1 according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE), except for loss of tendon reflex as the only symptom.
• Treatment for systemic infection within 14 days before initiating study treatment.
• Active inflammatory bowel disease, serious gastric ulceration or other bowel disease causing chronic diarrhoea (defined as > 4 loose stools per day).
• Suspected or known dihydropyrimidine dehydrogenase deficiency (DPD).
• Thrombosis or severe bleeding within six months prior to entry into the study (except for bleeding of the tumour before its surgical resection), evidence of bleeding diathesis or coagulopathy, or current or recent (within 10 days prior to initiation of study treatment) use of full-dose oral or parenteral anticoagulants for therapeutic purposes.
• History of any medical condition that may increase the risks associated with study participation or may interfere with the interpretation of the study results.
• Known positive test for human immunodeficiency virus infection, hepatitis C virus or chronic active hepatitis B infection.
• Known allergy to the investigational product, to any of its excipients, to monoclonal antibodies, or to any of the components of the chemotherapy regimen.
• Any co-morbid disease that would increase risk of toxicity.
• Any kind of disorder that compromises the ability of the subject to give written informed consent and/or comply with the study procedures.
• Any investigational agent or participation in another clinical trial within 30 days prior to randomisation.
• Must not have had a major surgical procedure within 28 days of randomisation.
• Subject who is pregnant or breast feeding.
• Woman or man of childbearing potential not consenting to use adequate contraceptive precautions (intrauterine contraceptive device, contraceptive implants, injectables (hormonal depot), transdermal hormonal contraception (contraceptive patch), sexual abstinence or vasectomised partner) during the course of the study and for six months after the last study drug administration for women and men. Post-menopausal women must have been amenorrheic for at least 12 months to be considered of non-child-bearing potential.
• Subject unwilling or unable to comply with study requirements.
• Hearing impairment