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    The EU Clinical Trials Register currently displays   37227   clinical trials with a EudraCT protocol, of which   6125   are clinical trials conducted with subjects less than 18 years old.
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    EudraCT Number:2007-004219-75
    Sponsor's Protocol Code Number:EMR200048-052
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2008-10-17
    Trial results View results
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    A. Protocol Information
    A.1Member State ConcernedUK - MHRA
    A.2EudraCT number2007-004219-75
    A.3Full title of the trial
    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.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    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.
    A.3.2Name or abbreviated title of the trial where available
    A.4.1Sponsor's protocol code numberEMR200048-052
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorMerck KGaA
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportMerck KGaA
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMerck KGaA
    B.5.2Functional name of contact pointCommunication Center
    B.5.3 Address:
    B.5.3.1Street AddressFrankfurter Landstraße 250
    B.5.3.2Town/ cityDarmstadt
    B.5.3.3Post code64293
    B.5.4Telephone number+49 6151 72 5200
    B.5.5Fax number+49 6151 72 2000
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D. name Erbitux 5 mg/ml
    D. of the Marketing Authorisation holderMerck KGaA
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCetuximab
    D.3.10 Strength
    D.3.10.1Concentration unit mg/l milligram(s)/litre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D. cell therapy medicinal product No
    D. therapy medical product No
    D. Engineered Product No
    D. ATIMP (i.e. one involving a medical device) No
    D. on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product Yes
    D. medicinal product typeMonoclonal antibody
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Advanced esophago-gastric cancer
    E.1.1.1Medical condition in easily understood language
    Gastric cancer
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level PT
    E.1.2Classification code 10017758
    E.1.2Term Gastric cancer
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    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.
    E.2.2Secondary objectives of the trial
    Secondary objectives are to assess cetuximab + XP versus XP alone with respect to overall survival, overall tumor response, quality of life and safety.
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    EXPAND (Erbitux in combination with Xeloda and cisplatin in advanced esophago-gastric cancer). Ancillary Study: Analysis of genetic variations from subjects randomized in main study protocol EMR 200048-052 Date: 18 April 2008 Version: Amendment 1 The objective of this ancillary study is to study the correlation between genetic variations, such as single nucleotide polymorphisms (SNPs) and copy number variations (CNVs), and response to treatment (capecitabine and cisplatin alone or in combination with cetuximab), especially concerning Ig gamma Fc receptor (FCGR) genes. Correlation with toxicity/adverse events and pharmacokinetics will be analyzed as part of the response to treatment.
    E.3Principal 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 to be based on the Cockroft-Gault formula for creatinine clearance: GFR (mL/min)=(C x (140-age [years] x weight [kg]))/(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)
    E.4Principal 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 6.8.2), 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
    E.5 End points
    E.5.1Primary end point(s)
    The primary study endpoint is progression-free survival
    E.5.1.1Timepoint(s) of evaluation of this end point
    Statistical analyses will be performed using data obtained until a clinical cut-off date, which is determined by the date when 631 PFS events are reported from IRC assessments or by March 31st 2012 (whichever occurs first).
    E.5.2Secondary end point(s)
    To assess cetuximab + XP versus XP alone with respect to: OS; overall response; QoL; safety
    E.5.2.1Timepoint(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.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans Information not present in EudraCT
    E.7.1.2Bioequivalence study Information not present in EudraCT
    E.7.1.3Other Information not present in EudraCT
    E. trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E. description
    Capecitabine, cisplatin
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA90
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Czech Republic
    Hong Kong
    Korea, Republic of
    Russian Federation
    United Kingdom
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The end of study will occur, when the following conditions are met: • The last subject has received the last dose of study treatment with a minimum follow-up of 30 days (around five times the upper range of the half-life of cetuximab) AND • At least 631 deaths have been reported
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years4
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero Information not present in EudraCT
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) Information not present in EudraCT
    F.1.1.3Newborns (0-27 days) Information not present in EudraCT
    F.1.1.4Infants and toddlers (28 days-23 months) Information not present in EudraCT
    F.1.1.5Children (2-11years) Information not present in EudraCT
    F.1.1.6Adolescents (12-17 years) Information not present in EudraCT
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 520
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 350
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2008-10-17. Yes
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state3
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 700
    F.4.2.2In the whole clinical trial 870
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Surviving patients will be under standard of care treatment after their participation in the trial has ended
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2008-11-21
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2009-03-05
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2013-02-17
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
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