Erbitux in Combination With Xeloda and Cisplatin in Advanced Esophago-gastric Cancer

Open-label, Randomized, Controlled, Multicenter Phase III Study Investigating Cetuximab in Combination With Capecitabine (Xeloda, X) and Cisplatin (P) Versus XP Alone as First-line Treatment for Subjects With Advanced Gastric Adenocarcinoma Including Adenocarcinoma of the Gastroesophageal Junction

The primary objective of this study is to demonstrate that addition of cetuximab to 1st-line treatment with capecitabine (Xeloda, X) and cisplatin (P) [XP] chemotherapy regimen has a clinically relevant benefit for subjects with advanced gastric adenocarcinoma including gastroesophageal junction (GEJ) adenocarcinoma, in terms of progression free survival (PFS).

Secondary objectives are to assess cetuximab plus XP versus XP alone with respect to overall survival, overall tumor response, quality of life (QoL) and safety.

Inclusion Criteria:

• Written informed consent before any study-related activities are carried out
• Age greater than or equal to (>=) 18 years
• Histologically confirmed adenocarcinoma of the stomach or gastroesophageal junction (Adenocarcinoma of the gastroesophageal junction [AEG] Types I-III according to Siewert classification)
• Archived tumor material sample for at least subsequent standardized Epidermal Growth Factor Receptor (EGFR) expression assessment
• Unresectable advanced (M0) or unresectable metastatic (M1) disease
• At least one radiographically documented measurable lesion in a previously non-irradiated area according to response evaluation criteria in solid tumors (RECIST). The primary tumor site is to be considered as a non-measurable lesion only
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Estimated life expectancy greater than (>) 12 weeks
• Medically accepted contraception (if the risk of conception exists)
• Glomerular filtration rate (GFR) >= 60 milliliter per minute (mL/min) The GFR is based on the Cockcroft-Gault formula for creatinine clearance
• Aspartate-aminotransferase (ASAT) less than or equal to (=<) 2.5 * upper limit of normal (ULN) and alanine-aminotransferase (ALAT) =< 2.5 *ULN
• Bilirubin =< 3 * ULN
• Absolute neutrophil count (ANC) >= 1.5 * 10^9 per liter
• Platelets >= 100 * 10^9 per liter
• Hemoglobin >=10 gram per deciliter (g/dL) (without transfusions)
• Sodium and potassium within normal limits or =< 10 percent above or below (supplementation permitted)

Exclusion Criteria:

• Prior chemotherapy, however, previous (neo-)adjuvant (radio-) chemotherapy allowed if finished > 1 year prior to start of study treatment and no more than 300 mg/m^2 cisplatin has been administered

• Prior treatment with an antibody or molecule targeting EGFR and/or Vascular Endothelial Growth Factor Receptor (VEGFR) related signaling pathways

• Brain metastasis and/or leptomeningeal disease (known or suspected)

• Radiotherapy (except localized radiotherapy for pain relief), major surgery or any investigational drug within 30 days before the start of study treatment

• Concurrent chronic systemic immune or hormone therapy not indicated in this study protocol (except for physiologic replacement)

• Clinically relevant coronary artery disease (New York Heart Association [NYHA] functional angina classification III/IV), congestive heart failure (NYHA III/IV), clinically relevant cardiomyopathy, history of myocardial infarction in the 12 months before study Screening, or high risk of uncontrolled arrhythmia

• Active Hepatitis B or C

• Chronic diarrhea or short bowel syndrome

• Presence of any contra-indication to treatment with cetuximab, capecitabine and cisplatin including:

  • Known hypersensitivity to capecitabine, fluorouracil, cisplatin, cetuximab or to any of the excipients of these drugs
  • Known dihydropyrimidine dehydrogenase (DPD) deficiency
  • Hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption
  • Current treatment with sorivudine or chemically related analogues, such as brivudine
  • Symptomatic peripheral neuropathy National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade >= 2 and/or ototoxicity NCI CTCAE Grade >= 2, except if due to trauma or mechanical impairment due to tumor mass

• Pregnancy or lactation period

• Concurrent treatment with a non-permitted drug

• Treatment in another clinical study within 30 days prior to study screening

• Previous malignancy other than gastric cancer within 5 years prior to study screening, except for basal cell cancer of the skin or pre-invasive cancer of the cervix

• Medical or psychological conditions that would not permit the subject to complete the study or sign informed consent

• Legal incapacity or limited legal capacity

• Significant disease which, in the Investigator's opinion, would exclude the subject from the study