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

Phase 3

Completed

Conditions: Gastric Cancer

Interventions: Drug: Cetuximab
Drug: Capecitabine
Drug: Cisplatin

Registration Number: NCT00678535

Lead Sponsor: Merck KGaA, Darmstadt, Germany

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 904

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cetuximab plus Capecitabine plus Cisplatin	Cisplatin	-
Cetuximab plus Capecitabine plus Cisplatin	Cetuximab	-
Cetuximab plus Capecitabine plus Cisplatin	Capecitabine	-
Capecitabine plus Cisplatin	Capecitabine	-
Capecitabine plus Cisplatin	Cisplatin	-

Primary Outcome Measures

Name	Time	Method
Progression-free Survival (PFS) Time: Independent Review Committee (IRC) Assessments	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 Outcome Measures

Name	Time	Method
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)	The OS time is defined as the time from randomization to death or last day known to be alive. Participants without event are censored at the last date known to be alive or at the clinical cut-off date, whatever is earlier.
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)	The BOR rate is defined as the percentage of participants having achieved complete response (CR) or partial response (PR) as the best overall response, based on radiological assessments (based on response evaluation criteria in solid tumors \[RECIST\] Version 1.0) from the IRC.
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)	Mean global health status and social functioning scores (EORTC QLQ-C30) against time for each treatment group. Scores were derived from mutually exclusive sets of items, with scale scores ranging from 0 to 100 after a linear transformation. Higher scores indicate a better QoL.
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)	An Adverse Event (AE) is defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to Baseline during a clinical study with an investigational medicinal product (IMP), regardless of causal relationship and even if no IMP has been administered.
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)	EQ-5D questionnaire is a measure of health status that provides a simple descriptive profile and a single index value. The EQ-5D defines health in terms of mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The 5 single items are combined to obtain a single index score that is health utility index (HUI) score reflecting subject's preferences for different health states. The lowest possible score is -0.59 and the highest is 1.00, higher scores on the EQ-5D represent a better QoL.