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

• Overall Survival [ Time Frame: Various Timepoints ] [ Designated as safety issue: No ]
• Overall Response [ Time Frame: Various Timepoints ] [ Designated as safety issue: No ]
• Quality of Life [ Time Frame: Various Timepoints ] [ Designated as safety issue: No ]
• Safety [ Time Frame: Various Timepoints ] [ Designated as safety issue: Yes ]

The primary objective of this study is to demonstrate that addition of cetuximab to 1st-line treatment with XP chemotherapy regimen has a clinically relevant benefit for subjects with advanced gastric adenocarcinoma including GEJ adenocarcinoma, in terms of PFS.

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

• Drug: Cetuximab + Capecitabine and Cisplatin
  q week + XP q 3 weeks
• Drug: Capecitabine and Cisplatin
  q 3 weeks

• Experimental: A
  Experimental drug + chemotherapy approved
  Intervention: Drug: Cetuximab + Capecitabine and Cisplatin
• Active Comparator: B
  Chemotherapy approved
  Intervention: Drug: Capecitabine and Cisplatin

Inclusion Criteria:

• Written informed consent before any study-related activities are carried out
• Age ≥ 18 years
• Histologically confirmed adenocarcinoma of the stomach or gastroesophageal junction (AEG types I-III according to Siewert classification)
• Archived tumor material sample for at least subsequent standardized EGFR expression assessment. Investigators must make sure in advance that appropriate archived tumor material is available from a potentially eligible subject, and that a sample can be shipped to a central repository if the subject agrees to participate.
• Unresectable advanced (M0) or unresectable metastatic (M1) disease
• At least one radiographically documented measurable lesion in a previously non-irradiated area according to RECIST
• ECOG performance status 0-1
• Estimated life expectancy > 12 weeks
• Medically accepted contraception (if the risk of conception exists)
• Glomerular filtration rate ≥ 60mL/min
• ASAT ≤ 2.5 x ULN and ALAT ≤ 2.5 x ULN
• Bilirubin ≤ 3 x ULN
• ANC ≥ 1.5 x 10 to the power of 9/L
• Platelets ≥ 100 x 10 to the power of 9/L
• Hemoglobin ≥ 10 g/dL (without transfusions)
• Sodium and potassium within normal limits or ≤ 10% 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/m2 cisplatin has been administered
• Prior treatment with an antibody or molecule targeting EGFR- and/or 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 in the 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