Clinical trial NCT00678535: Erbitux in Combination With Xeloda and Cisplatin in Advanced Esophago-gastric Cancer
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Gastric Cancer
Keywords: 1st line treatment for Gastric Cancer
Cetuximab
Capecitabine
Xeloda
Cisplatin
Progression-free survival
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2008-05-15
Enrollment: 904
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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
* 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

Primary outcomes:
measure: Progression-free Survival (PFS) Time: Independent Review Committee (IRC) Assessments
timeFrame: 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 outcomes:
measure: Overall Survival (OS)
timeFrame: 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)
measure: Best Overall Response (BOR) Rate: Independent Review Committee (IRC) Assessments
timeFrame: Every 6 weeks until progression, reported between day of first participant randomized, that is, 30 Jun 2008 until cut-off date, (31 Mar 2012)
measure: Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)
timeFrame: 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)
measure: Quality of Life (QoL) Assessed by EuroQol 5Dimensions (EQ-5D) Questionnaire
timeFrame: 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)
measure: Safety - Number of Participants With Adverse Events (AEs)
timeFrame: 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)
Other outcomes:
Locations:
city: Rosario
country: Argentina
facility: Research site
city: Coburg VIC
country: Australia
facility: Research site
city: Frankston, VIC
country: Australia
facility: Research site
city: Perth
country: Australia
facility: Research site
city: Graz
country: Austria
facility: Research site
city: Kufstein
country: Austria
facility: Research site
city: Steyr
country: Austria
facility: Research site
city: Wien
country: Austria
facility: Research Site
city: Zams
country: Austria
facility: Research Site
city: Bonheiden
country: Belgium
facility: Research Site
city: Bruxelles
country: Belgium
facility: Research Site
city: Verviers
country: Belgium
facility: Research site
city: Campinas
country: Brazil
facility: Research site
city: Ijui
country: Brazil
facility: Research site
city: Jaú
country: Brazil
facility: Research site
city: Porto Alegre
country: Brazil
facility: Research site
city: Salvador
country: Brazil
facility: Research site
city: Santo André
country: Brazil
facility: Research site
city: Sâo Paulo
country: Brazil
facility: Research site
city: Pleven
country: Bulgaria
facility: Research site
city: Plovdiv
country: Bulgaria
facility: Research site
city: Rousse
country: Bulgaria
facility: Research site
city: Sofia
country: Bulgaria
facility: Research site
city: Reñaca
country: Chile
facility: Research site
city: Santiago
country: Chile
facility: Research site
city: Temuco
country: Chile
facility: Research site
city: Valparaiso
country: Chile
facility: Research site
city: Beijing
country: China
facility: Research site
city: Guangzhou
country: China
facility: Research site
city: Hefei
country: China
facility: Research site
city: Nanjing
country: China
facility: Research site
city: Shanghai
country: China
facility: Research site
city: Shenyang
country: China
facility: Research site
city: Brno
country: Czech Republic
facility: Research Site
city: Hradec Králové
country: Czech Republic
facility: Research Site
city: Prague 5
country: Czech Republic
facility: Research site
city: Besancon
country: France
facility: Research site
city: Clermont Ferrand Cedex 1
country: France
facility: Research site
city: La Roche sur Yon
country: France
facility: Research site
city: Marseille
country: France
facility: Research site
city: Paris 14
country: France
facility: Research site
city: Rennes
country: France
facility: Research site
city: Berlin
country: Germany
facility: Research Site
city: Bielefeld
country: Germany
facility: Research site
city: Braunschweig
country: Germany
facility: Research site
city: Dresden
country: Germany
facility: Research Site
city: Essen
country: Germany
facility: Research Site
city: Esslingen
country: Germany
facility: Research site
city: Frankfurt
country: Germany
facility: Research site
city: Giessen
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Heidelberg
country: Germany
facility: Research Site
city: Köln
country: Germany
facility: Research site
city: Ludwigshafen
country: Germany
facility: Research site
city: Mainz
country: Germany
facility: Research Site
city: München
country: Germany
facility: Research Site
city: Offenbach
country: Germany
facility: Research site
city: Regensburg
country: Germany
facility: Research Site
city: Schweinfurt
country: Germany
facility: Research site
city: Schwäbisch Hall
country: Germany
facility: Research Site
city: Stuttgart
country: Germany
facility: Research site
city: Timisoara
country: Germany
facility: Research Site
city: Troisdorf
country: Germany
facility: Research Site
city: Ulm
country: Germany
facility: Research site
city: Weiden
country: Germany
facility: Research site
city: Weilheim
country: Germany
facility: Research Site
city: Ioannina
country: Greece
facility: Research site
city: Thessaloniki
country: Greece
facility: Research site
city: Hong Kong
country: Hong Kong
facility: Research site
city: Budapest
country: Hungary
facility: Research site
city: Gyor
country: Hungary
facility: Research site
city: Kaposvar
country: Hungary
facility: Research Site
city: Tatabanya
country: Hungary
facility: Research Site
city: Haifa
country: Israel
facility: Research site
city: Jerusalem
country: Israel
facility: Research site
city: Petach Tiqva
country: Israel
facility: Research site
city: Ramat Gan
country: Israel
facility: Research site
city: Tel Aviv
country: Israel
facility: Research site
city: Ancona
country: Italy
facility: Research site
city: Bologna
country: Italy
facility: Research site
city: Milano
country: Italy
facility: Research site
city: Napoli
country: Italy
facility: Research site
city: Roma
country: Italy
facility: Research site
city: Rozzano (Milano)
country: Italy
facility: Research site
city: Chiba
country: Japan
facility: Research site
city: Ehime
country: Japan
facility: Research site
city: Hokkaido
country: Japan
facility: Research site
city: Koto-ku
country: Japan
facility: Research site
city: Nagoya
country: Japan
facility: Research site
city: Osaka
country: Japan
facility: Research site
city: Saitama
country: Japan
facility: Research site
city: Shizuoka
country: Japan
facility: Research site
city: Tochigi
country: Japan
facility: Research site
city: Tokyo
country: Japan
facility: Research site
city: Yokohama
country: Japan
facility: Research site
city: Anyang
country: Korea, Republic of
facility: Research site
city: Daegu
country: Korea, Republic of
facility: Research site
city: Inchon-si
country: Korea, Republic of
facility: Research site
city: Seongnam
country: Korea, Republic of
facility: Research site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Gdańsk
country: Poland
facility: Research site
city: Lublin
country: Poland
facility: Research site
city: Opole
country: Poland
facility: Research site
city: Wroclaw
country: Poland
facility: Research site
city: Sana Maria da Feira
country: Portugal
facility: Research site
city: Baia-Mare
country: Romania
facility: Research site
city: Bucharest
country: Romania
facility: Research Site
city: Cluj-Napoca
country: Romania
facility: Research Site
city: Iasi
country: Romania
facility: Research Site
city: Timisoara
country: Romania
facility: Research site
city: Kazan
country: Russian Federation
facility: Research site
city: Moscow
country: Russian Federation
facility: Research site
city: Obninsk
country: Russian Federation
facility: Research site
city: Saint-Petersburg
country: Russian Federation
facility: Research site
city: Alicante
country: Spain
facility: Research Site
city: El Palmar-Murcia
country: Spain
facility: Research site
city: Lugo
country: Spain
facility: Research site
city: Pamplona
country: Spain
facility: Research site
city: Santander
country: Spain
facility: Research Site
city: Seville
country: Spain
facility: Research site
city: Valencia
country: Spain
facility: Research Site
city: Changhua
country: Taiwan
facility: Research site
city: Kaohsiung County
country: Taiwan
facility: Research site
city: Kaohsiung
country: Taiwan
facility: Research site
city: Taichung City
country: Taiwan
facility: Research site
city: Tainan
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taoyuan
country: Taiwan
facility: Research site
city: Guildford
country: United Kingdom
facility: Research site
city: Manchester
country: United Kingdom
facility: Research site
Study officials:
affiliation: University Clinic Leipzig, University Cancer Center Leipzig (UCCL), Leipzig Germany
name: Florian Lordick, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: