Clinical trial to investigate cetuximab in combination with capecitabine and cisplatin versus capecitabine and cisplatin alone as first-line treatment for patients with advanced gastric cancer.

Conditions: Advanced esophago-gastric cancer
Therapeutic area: Diseases [C] - Cancer [C04]
MedDRA version: 14.1Level: PTClassification code 10017758Term: Gastric cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Registration Number: EUCTR2007-004219-75-HU

Lead Sponsor: Merck KGaA

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 870

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, see appendix A)
Diagnosis should be based on recently obtained tumor material. The histological sample on which the diagnosis is based must have been obtained no more than 2 years before enrolment into this study.
• 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
In the event of unresectable advanced disease, at least one measurable locoregional
lymph node or other measurable extraluminal tumor lesion = 2cm must be documented (irrespective of whether it is measured by conventional techniques or spiral CT scan).
• At least one radiographically documented measurable lesion in a previously nonirradiated area according to RECIST, i.e. this lesion must be adequately measurable in at least one dimension (longest diameter to be recorded) as = 2cm by conventional techniques or = 1 cm by spiral CT scan (see section 7.2). Primary tumor site will be considered as a non-measurable lesion only.
• ECOG performance status 0-1
• Estimated life expectancy > 12 weeks
• Medically accepted contraception (if the risk of conception exists)
• Glomerular filtration rate (GFR) = 60mL/min
The GFR is e.g. to be based on the Cockroft-Gault formula for creatinine clearance:
C x (140-age [years]) x weight [kg]
GFR (mL/min) = ?????????????
72 x serum creatinine (mg/dL)
where C = 0.85 for female subjects and C = 1.00 for male subjects
• ASAT = 2.5 x ULN and ALAT = 2.5 x ULN
• Bilirubin = 3 x ULN
• ANC = 1.5 x 109/L
• Platelets = 100 x 109/L
• Hemoglobin = 10 g/dL (without transfusions)
• Sodium and potassium within normal limits or = 10% above or below (supplementation permitted)

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 520
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 350

Exclusion Criteria

Prior chemotherapy. However previous (neo-)adjuvant (radio-)chemotherapy is allowed if it was 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 as outlined in section 6.8.1), 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)
• Clinically relevant coronary artery disease (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
• 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
• Subjects with 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 NCI-CTCAE grade = 2 and/or ototoxicity
NCI-CTC AE 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 (see section 6.8.2)
• Treatment in another clinical study within the past 30 days
• Previous malignancy other than gastric cancer in the last 5 years except for basal cell cancer of the skin or preinvasive 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 clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: 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 Objective: Secondary objectives are to assess cetuximab + XP versus XP alone with respect to overall survival, overall tumor response, quality of life and safety.;Primary end point(s): The primary study endpoint is progression-free survival;Timepoint(s) of evaluation of this end point: Statistical analyses will be performed using data obtained until a clinical cut-off date, which is<br>determined by the date when 631 PFS events are reported from IRC assessments or by March 31st 2012 (whichever occurs first).

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): To assess cetuximab + XP versus XP<br>alone with respect to: OS; overall response; QoL; safety;Timepoint(s) of evaluation of this end point: Study planning for overall survival suggests at least 631 deaths are necessary to detect a hazard ratio of 0.8 with 80% power given a median survival time of 10 months in the control group. Therefore, subjects need to be followed-up for approximately 4 years after study start.