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

Merck KGaA, Darmstadt, Germany2 sites in 2 countries904 target enrollmentJune 2008

ConditionsGastric Cancer

InterventionsCetuximab Capecitabine Cisplatin

DrugsCetuximab Capecitabine Cisplatin

Overview

Phase: Phase 3
Intervention: Cetuximab
Conditions: Gastric Cancer
Sponsor: Merck KGaA, Darmstadt, Germany
Enrollment: 904
Locations: 2
Primary Endpoint: Progression-free Survival (PFS) Time: Independent Review Committee (IRC) Assessments
Status: Completed
Last Updated: 11 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief 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.

Registry

clinicaltrials.gov

Start Date

June 2008

End Date

February 2013

Last Updated

11 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Merck KGaA, Darmstadt, Germany

Responsible Party

Sponsor

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

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

Arms & Interventions

Cetuximab plus Capecitabine plus Cisplatin

Intervention: Cetuximab

Cetuximab plus Capecitabine plus Cisplatin

Intervention: Capecitabine

Cetuximab plus Capecitabine plus Cisplatin

Intervention: Cisplatin

Capecitabine plus Cisplatin

Intervention: Capecitabine

Capecitabine plus Cisplatin

Intervention: Cisplatin

Outcomes

Primary Outcomes

Progression-free Survival (PFS) Time: Independent Review Committee (IRC) Assessments

Time Frame: Time from randomization to disease progression, death or last tumor assessment, reported between day of first participant randomized, that is, 30 Jun 2008 until cut-off date (31 Mar 2012)

The PFS time is defined as the duration from randomization to either first observation of progressive disease (PD) or occurrence of death due to any cause within 60 days of the last tumor assessment or randomization. Participants without event are censored on the date of last tumor assessment.

Secondary Outcomes

Overall Survival (OS)(Time from randomization to death or last day known to be alive, reported between day of first participant randomized, that is, 30 Jun 2008 until cut-off date, (31 Mar 2012))
Best Overall Response (BOR) Rate: Independent Review Committee (IRC) Assessments(Every 6 weeks until progression, reported between day of first participant randomized, that is, 30 Jun 2008 until cut-off date, (31 Mar 2012))
Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)(Baseline, Week 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60, reported between day of first participant randomized, that is, 30 Jun 2008 until cut-off date (31 Mar 2012))
Safety - Number of Participants With Adverse Events (AEs)(Time from first dose up to Day 30 after last dose of study treatment, reported between day of first participant randomized, that is, 30 Jun 2008 until cut-off date (31 Mar 2012))
Quality of Life (QoL) Assessed by EuroQol 5Dimensions (EQ-5D) Questionnaire(Baseline, Week 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60, reported between day of first participant randomized, that is, 30 Jun 2008 until cut-off date (31 Mar 2012))