Erbitux in Combination With Xeloda and Cisplatin in Advanced Esophago-gastric Cancer
Condition: Gastric Cancer
MeSH terms: Stomach Neoplasms
Intervention: Cetuximab; Capecitabine; Cisplatin
Intervention description: Single first dose of cetuximab 400 milligram per square meter (mg/m^2) will be administered intravenously over 120 minutes followed by weekly intravenous infusion of cetuximab 250 mg/m^2 over 60 minutes in each 3-week treatment cycle, until documented disease progression, unacceptable toxicity, or withdrawal of consent.; Capecitabine 1000 mg/m^2 will be administered orally twice daily from evening of Day 1 to morning of Day 15 for every 3-week treatment cycle, until documented disease progression, unacceptable toxicity, or withdrawal of consent.; Cisplatin 80 mg/m^2 will be administered intravenously with infusion over 1 to 4 hours on Day 1 of each 3-week treatment cycle, until documented disease progression, unacceptable toxicity, or withdrawal of consent.
Intervention MeSH terms: Capecitabine; Cetuximab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 904.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: 1st line treatment for Gastric Cancer; Cetuximab; Capecitabine; Xeloda; Cisplatin; Progression-free survival

Summary:

      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.
    

Eligibility criteria:

        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