Cetuximab in Combination With S-1 and Cisplatin in Gastric Cancer

Study Overview
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Brief Summary
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This open-label, single-arm, multicenter, Phase 2 trial will treat at least 40 participants with advanced gastric adenocarcinoma including adenocarcinoma of the gastroesophageal junction (GEJ) who have not previously received systemic chemotherapy for this setting. All eligible participants will receive the combination of cetuximab plus S-1 (a combination of tegafur, gimeracil, and oteracil) and cisplatin.

Official Title
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Open-label, Single-arm, Multicenter Phase II Trial Investigating Cetuximab in Combination With S-1 and Cisplatin as First-line Treatment for Patients With Advanced Gastric Adenocarcinoma Including Adenocarcinoma of the Gastroesophageal Junction

Conditions
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Gastric Cancer

Intervention / Treatment
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* Drug: Cetuximab
* Drug: Cisplatin
* Drug: S-1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent and agreement with medically accepted contraception (in participants with conception potential) are obtained Japanese participants aged greater than or equal to 20 years Histologically confirmed adenocarcinoma of the stomach or GEJ (adenocarcinomas of the esophagogastric junction types I to III according to Siewert's classification) in Stage M0 (unresectable advanced) or Stage M1 (unresectable metastatic) of the disease Archived tumor material sample for at least subsequent standardized epidermal growth factor receptor (EGFR) expression and Kirsten-rat sarcoma (KRAS) mutation assessments At least one radiographically documented measurable lesion in a previously non-irradiated area according to the RECIST v 1.0 Eastern Cooperative Oncology Group - performance status (ECOG-PS) 0 to 1 Estimated life expectancy greater than 12 weeks Renal, liver and hematopoietic function as defined in the protocol. Sodium and potassium within normal limits or as defined in the protocol Other protocol defined inclusion criteria could apply Exclusion Criteria: Prior therapies: prior treatment with an antibody or molecule targeting EGFR- and/or vascular endothelial growth factor (VEGF) receptor-related signaling pathways; chemotherapies; or radiotherapies, major surgeries, and any investigational drugs in the 30 days before the start of trial treatment Concurrent chronic systemic immune or hormone therapy not indicated in this trial protocol any contraindication to treatment with cetuximab and cisplatin, or any treatments with prohibited concomitant drugs Brain metastasis and/or leptomeningeal disease 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 last 12 months, or high risk of uncontrolled arrhythmia Chronic diarrhea or short bowel syndrome Known Human Immunodeficiency Virus (HIV) infection, active or chronic carrier of hepatitis B virus (HBV) (HBV antigen positive or HBV deoxyribonucleic acid (DNA) positive) or hepatitis C virus (HCV) (HCV antibody positive) Pregnancy or lactation period Concurrent treatment with a non-permitted drug (any other chemotherapy, systemic anticancer therapy or immunotherapy) Previous malignancy other than gastric cancer in the last 5 years Medical or psychological conditions that would not permit the participant to complete the trial or sign the Informed Consent Form (ICF) Legal incapacity or limited legal capacity Other protocol defined exclusion criteria could apply

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cetuximab plus cisplatin plus S-1<br> | Drug: Cetuximab<br>* Single first dose of cetuximab 400 milligram per square meter (mg/m^2) will be administered intravenously followed by once weekly subsequent intravenous infusion of cetuximab 250 mg/m^2 in each 5-week treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent.<br>Drug: Cisplatin<br>* Cisplatin 60 mg/m^2 will administered as intravenous infusion on Day 8 of each 5-week cycle maximum up to 8 cycles until disease progression, unacceptable toxicity, or withdrawal of consent<br>Drug: S-1<br>* S-1, a combination of tegafur, gimeracil, and oteracil will be administered intravenously at a dose of 40 to 60 mg/m^2 orally twice daily for first three consecutive weeks of 5-week cycle until disease progression, unacceptable toxicity, or withdrawal of consent.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Overall Response (BOR) Rate - Independent Review Committee (IRC) Assessments | The best overall response rate is defined as the percentage of participants having achieved confirmed complete response plus partial response as the best overall response according to radiological assessments (based on Response Evaluation Criteria in Solid Tumors version 1.0 [RECIST v 1.0] criteria). | Evaluations were performed every 6 weeks until disease progression, reported between day of first participant treated, that is July 2011, until cut-off date, (14 August 2012) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Progression-free Survival (PFS) Time - Independent Review Committee (IRC) Assessments | The PFS time is defined as the duration from start of treatment until radiological progression (based on RECIST v 1.0 criteria) or death due to any cause within 60 days of the last tumor assessment or start of treatment. Participants without event are censored on the date of last tumor assessment. | Time from start of treatment to disease progression, death or last tumor assessment, reported between day of first participant treated, that is July 2011, until cut-off date, (14 August 2012) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gastric Cancer, Cetuximab, EMD271786, TS-1, Cisplatin