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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00678535




Registration number
NCT00678535
Ethics application status
Date submitted
13/05/2008
Date registered
15/05/2008
Date last updated
21/07/2014

Titles & IDs
Public title
Erbitux in Combination With Xeloda and Cisplatin in Advanced Esophago-gastric Cancer
Scientific title
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
Secondary ID [1] 0 0
2007-004219-75
Secondary ID [2] 0 0
EMR 200048-052
Universal Trial Number (UTN)
Trial acronym
EXPAND
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Gastric Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Stomach

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cetuximab
Treatment: Drugs - Capecitabine
Treatment: Drugs - Cisplatin

Experimental: Cetuximab plus Capecitabine plus Cisplatin -

Active comparator: Capecitabine plus Cisplatin -


Treatment: Drugs: Cetuximab
Single first dose of cetuximab 400 milligram per square meter (mg/m\^2) will be administered intravenously over 120 minutes followed by weekly intravenous infusion of cetuximab 250 mg/m\^2 over 60 minutes in each 3-week treatment cycle, until documented disease progression, unacceptable toxicity, or withdrawal of consent.

Treatment: Drugs: Capecitabine
Capecitabine 1000 mg/m\^2 will be administered orally twice daily from evening of Day 1 to morning of Day 15 for every 3-week treatment cycle, until documented disease progression, unacceptable toxicity, or withdrawal of consent.

Treatment: Drugs: Cisplatin
Cisplatin 80 mg/m\^2 will be administered intravenously with infusion over 1 to 4 hours on Day 1 of each 3-week treatment cycle, until documented disease progression, unacceptable toxicity, or withdrawal of consent.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free Survival (PFS) Time: Independent Review Committee (IRC) Assessments
Timepoint [1] 0 0
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)
Secondary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
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)
Secondary outcome [2] 0 0
Best Overall Response (BOR) Rate: Independent Review Committee (IRC) Assessments
Timepoint [2] 0 0
Every 6 weeks until progression, reported between day of first participant randomized, that is, 30 Jun 2008 until cut-off date, (31 Mar 2012)
Secondary outcome [3] 0 0
Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)
Timepoint [3] 0 0
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)
Secondary outcome [4] 0 0
Quality of Life (QoL) Assessed by EuroQol 5Dimensions (EQ-5D) Questionnaire
Timepoint [4] 0 0
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)
Secondary outcome [5] 0 0
Safety - Number of Participants With Adverse Events (AEs)
Timepoint [5] 0 0
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)

Eligibility
Key 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)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/06/2008
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/02/2013
Sample size
Target
Accrual to date
Final
904
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research site - Coburg VIC
Recruitment hospital [2] 0 0
Research site - Frankston, VIC
Recruitment hospital [3] 0 0
Research site - Perth
Recruitment postcode(s) [1] 0 0
- Coburg VIC
Recruitment postcode(s) [2] 0 0
- Frankston, VIC
Recruitment postcode(s) [3] 0 0
- Perth
Recruitment outside Australia
Country [1] 0 0
Argentina
State/province [1] 0 0
Rosario
Country [2] 0 0
Austria
State/province [2] 0 0
Graz
Country [3] 0 0
Austria
State/province [3] 0 0
Kufstein
Country [4] 0 0
Austria
State/province [4] 0 0
Steyr
Country [5] 0 0
Austria
State/province [5] 0 0
Wien
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Austria
State/province [6] 0 0
Zams
Country [7] 0 0
Belgium
State/province [7] 0 0
Bonheiden
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Belgium
State/province [8] 0 0
Bruxelles
Country [9] 0 0
Belgium
State/province [9] 0 0
Verviers
Country [10] 0 0
Brazil
State/province [10] 0 0
Campinas
Country [11] 0 0
Brazil
State/province [11] 0 0
Ijui
Country [12] 0 0
Brazil
State/province [12] 0 0
Jaú
Country [13] 0 0
Brazil
State/province [13] 0 0
Porto Alegre
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Brazil
State/province [14] 0 0
Salvador
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Brazil
State/province [15] 0 0
Santo André
Country [16] 0 0
Brazil
State/province [16] 0 0
Sâo Paulo
Country [17] 0 0
Bulgaria
State/province [17] 0 0
Pleven
Country [18] 0 0
Bulgaria
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Plovdiv
Country [19] 0 0
Bulgaria
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Rousse
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Bulgaria
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Sofia
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Chile
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Reñaca
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Chile
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Santiago
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Chile
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Temuco
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Chile
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Valparaiso
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China
State/province [25] 0 0
Beijing
Country [26] 0 0
China
State/province [26] 0 0
Guangzhou
Country [27] 0 0
China
State/province [27] 0 0
Hefei
Country [28] 0 0
China
State/province [28] 0 0
Nanjing
Country [29] 0 0
China
State/province [29] 0 0
Shanghai
Country [30] 0 0
China
State/province [30] 0 0
Shenyang
Country [31] 0 0
Czech Republic
State/province [31] 0 0
Brno
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Czech Republic
State/province [32] 0 0
Hradec Králové
Country [33] 0 0
Czech Republic
State/province [33] 0 0
Prague 5
Country [34] 0 0
France
State/province [34] 0 0
Besancon
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France
State/province [35] 0 0
Clermont Ferrand Cedex 1
Country [36] 0 0
France
State/province [36] 0 0
La Roche sur Yon
Country [37] 0 0
France
State/province [37] 0 0
Marseille
Country [38] 0 0
France
State/province [38] 0 0
Paris 14
Country [39] 0 0
France
State/province [39] 0 0
Rennes
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Germany
State/province [40] 0 0
Berlin
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Germany
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Bielefeld
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Germany
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Braunschweig
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Germany
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Dresden
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Germany
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Essen
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Germany
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Esslingen
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Germany
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Frankfurt
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Germany
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Giessen
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Germany
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Hamburg
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Germany
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Heidelberg
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Germany
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Köln
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Germany
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Ludwigshafen
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Germany
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Mainz
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Germany
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München
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Germany
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Offenbach
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Germany
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Regensburg
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Germany
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Schweinfurt
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Germany
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Schwäbisch Hall
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Germany
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Stuttgart
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Germany
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Timisoara
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Germany
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Troisdorf
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Germany
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Ulm
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Germany
State/province [62] 0 0
Weiden
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Germany
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Weilheim
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Greece
State/province [64] 0 0
Ioannina
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Greece
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Thessaloniki
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Hong Kong
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Hong Kong
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Hungary
State/province [67] 0 0
Budapest
Country [68] 0 0
Hungary
State/province [68] 0 0
Gyor
Country [69] 0 0
Hungary
State/province [69] 0 0
Kaposvar
Country [70] 0 0
Hungary
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Tatabanya
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Israel
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Haifa
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Israel
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Jerusalem
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Israel
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Petach Tiqva
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Israel
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Ramat Gan
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Israel
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Tel Aviv
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Italy
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Ancona
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Italy
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Bologna
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Milano
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Italy
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Napoli
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Italy
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Roma
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Italy
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Rozzano (Milano)
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Japan
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Chiba
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Ehime
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Hokkaido
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Koto-ku
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Nagoya
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Japan
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Osaka
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Japan
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Saitama
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Japan
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Shizuoka
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Japan
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Tochigi
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Japan
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Tokyo
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Japan
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Yokohama
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Korea, Republic of
State/province [93] 0 0
Anyang
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Korea, Republic of
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Daegu
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Korea, Republic of
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Inchon-si
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Korea, Republic of
State/province [96] 0 0
Seongnam
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Korea, Republic of
State/province [97] 0 0
Seoul
Country [98] 0 0
Poland
State/province [98] 0 0
Gdansk
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Poland
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Lublin
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Poland
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Opole
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Poland
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Wroclaw
Country [102] 0 0
Portugal
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Sana Maria da Feira
Country [103] 0 0
Romania
State/province [103] 0 0
Baia-Mare
Country [104] 0 0
Romania
State/province [104] 0 0
Bucharest
Country [105] 0 0
Romania
State/province [105] 0 0
Cluj-Napoca
Country [106] 0 0
Romania
State/province [106] 0 0
Iasi
Country [107] 0 0
Romania
State/province [107] 0 0
Timisoara
Country [108] 0 0
Russian Federation
State/province [108] 0 0
Kazan
Country [109] 0 0
Russian Federation
State/province [109] 0 0
Moscow
Country [110] 0 0
Russian Federation
State/province [110] 0 0
Obninsk
Country [111] 0 0
Russian Federation
State/province [111] 0 0
Saint-Petersburg
Country [112] 0 0
Spain
State/province [112] 0 0
Alicante
Country [113] 0 0
Spain
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El Palmar-Murcia
Country [114] 0 0
Spain
State/province [114] 0 0
Lugo
Country [115] 0 0
Spain
State/province [115] 0 0
Pamplona
Country [116] 0 0
Spain
State/province [116] 0 0
Santander
Country [117] 0 0
Spain
State/province [117] 0 0
Seville
Country [118] 0 0
Spain
State/province [118] 0 0
Valencia
Country [119] 0 0
Taiwan
State/province [119] 0 0
Changhua
Country [120] 0 0
Taiwan
State/province [120] 0 0
Kaohsiung County
Country [121] 0 0
Taiwan
State/province [121] 0 0
Kaohsiung
Country [122] 0 0
Taiwan
State/province [122] 0 0
Taichung City
Country [123] 0 0
Taiwan
State/province [123] 0 0
Tainan
Country [124] 0 0
Taiwan
State/province [124] 0 0
Taipei
Country [125] 0 0
Taiwan
State/province [125] 0 0
Taoyuan
Country [126] 0 0
United Kingdom
State/province [126] 0 0
Guildford
Country [127] 0 0
United Kingdom
State/province [127] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck KGaA, Darmstadt, Germany
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT00678535
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Florian Lordick, MD, PhD
Address 0 0
University Clinic Leipzig, University Cancer Center Leipzig (UCCL), Leipzig Germany
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00678535