Clinical trial NCT00125034: Oxaliplatin and Cetuximab in First-line Treatment of Metastatic Colorectal Cancer (mCRC)
Official title: Open, Randomized, Controlled, Multicenter Phase II Study Comparing 5-FU/FA Plus Oxaliplatin (FOLFOX-4) Plus Cetuximab Versus 5-FU/FA Plus Oxaliplatin (FOLFOX-4) as First-line Treatment for Epidermal Growth Factor Receptor-expressing Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neoplasm Metastasis
Colorectal Cancer
Keywords: FOLFOX-4
Cetuximab
First-line mCRC
EGFR positive
metastatic CRC
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2005-07-29
Enrollment: 344
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: This is an open label, randomized, controlled, multicenter phase II study comparing 5-FU/FA + oxaliplatin (FOLFOX-4) + cetuximab versus 5-FU/FA + oxaliplatin as first-line treatment for epidermal growth factor receptor (EGFR)-expressing mCRC.


Eligibility criteria: Inclusion Criteria:

* First-line mCRC
* EGFR positive
* Bi-dimensional measurable index lesion

Exclusion Criteria:

* Previous exposure to EGFR-targeting therapy
* Previous oxaliplatin-based therapy
* Previous chemotherapy for colorectal cancer except adjuvant treatment with progression of disease documented \> 6 months after end of adjuvant treatment
* Radiotherapy
* Surgery
* Any other investigational drug in the 30 days before randomization
* Brain metastasis and/or leptomeningeal disease
* Acute or sub-acute intestinal occlusion or history of inflammatory bowel disease

Primary outcomes:
measure: Best Overall Response Rate - Independent Review Committee (IRC)
timeFrame: Evaluations were performed every 6 weeks until progression, reported between day of first patient randomised, 27 Jul 2005, until cut-off date 4 August 2006
Secondary outcomes:
measure: Best Overall Response Rate (Chinese V-Ki-ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) Wild-Type Population)
timeFrame: Evaluations were performed every 6 weeks until progression, reported between day of first patient randomised, 27 Jul 2005, until cut-off date 1 Mar 2007
measure: Best Overall Response Rate (KRAS Mutant Population)
timeFrame: Evaluations were performed every 6 weeks until progression, reported between day of first patient randomised, 27 Jul 2005, until cut-off date 1 Mar 2007
measure: Progression-free Survival Time
timeFrame: Time from randomisation to disease progression, death or last tumour assessment, reported between day of first patient randomised, 27 Jul 2005, until cut-off date 01 Mar 2007
measure: Progression-free Survival Time (KRAS Wild-Type Population)
timeFrame: Time from randomisation to disease progression, death or last tumour assessment, reported between day of first patient randomised, 27 Jul 2005, until cut-off date 30 Nov 2008
measure: Progression-free Survival Time (KRAS Mutant Population)
timeFrame: Time from randomisation to disease progression, death or last tumour assessment, reported between day of first patient randomised, 27 Jul 2005, until cut-off date 30 Nov 2008
measure: Overall Survival Time
timeFrame: Time from randomisation to death or last day known to be alive, reported between day of first patient randomised, 27 Jul 2005, until cut-off date 30 Nov 2008
measure: Overall Survival Time (KRAS Wild-Type Population)
timeFrame: Time from randomisation to death or last day known to be alive, reported between day of first patient randomised, 27 Jul 2005, until cut-off date 30 November 2008
measure: Overall Survival Time (KRAS Mutant Population)
timeFrame: Time from randomisation to death or last day known to be alive, reported between day of first patient randomised, 27 Jul 2005, until cut-off date 30 November 2008
measure: Participants With No Residual Tumor After Metastatic Surgery
timeFrame: Time from first dose up to 30 days after the last dose of study treatment, reported between day of first patient randomised, 27 Jul 2005, until cut-off date 30 November 2008
measure: Disease Control Rate (Cut Off Date 4 August 2006)
timeFrame: Evaluations were performed every 6 weeks until progression, reported between day of first patient randomised, 27 Jul 2005, until cut-off date 4 August 2006
measure: Duration of Response
timeFrame: Time from first assessment of Complete Response or Partial Response to disease progression,death or last tumor assessment, reported between day of first patient randomised, 27 Jul 2005, until cut-off date 01 Mar 2007
measure: Safety - Number of Patients Experiencing Any Adverse Event
timeFrame: time from first dose up to 30 after last dose of study treatment, reported between day of first patient dose of study treatment, 27 Jul 2005, until cut-off date 30 Nov 2008
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Research Site
city: Linz
country: Austria
facility: Research Site
city: Salzburg
country: Austria
facility: Research Site
city: Wien
country: Austria
facility: Research Site
city: Zams
country: Austria
facility: Research Site
city: Antwerpen
country: Belgium
facility: Research Site
city: Bonheiden
country: Belgium
facility: Research Site
city: Brugge
country: Belgium
facility: Research Site
city: Hasselt
country: Belgium
facility: Research Site
city: Leuven
country: Belgium
facility: Research Site
city: Roeselare
country: Belgium
facility: Research Site
city: Turnhout
country: Belgium
facility: Research Site
city: ZU Gent
country: Belgium
facility: Research Site
city: Besancon
country: France
facility: Research Site
city: Clermond Ferrand
country: France
facility: Research Site
city: Clichy
country: France
facility: Research Site
city: Montpellier
country: France
facility: Research Site
city: Paris
country: France
facility: Research Site
city: Rouen
country: France
facility: Research Site
city: Strasbourg
country: France
facility: Research Site
city: Aschaffenburg
country: Germany
facility: Research Site
city: Dresden
country: Germany
facility: Research Site
city: Essen
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Kiel
country: Germany
facility: Research Site
city: Magdeburg
country: Germany
facility: Research Site
city: Mannheim
country: Germany
facility: Research Site
city: Nürnberg
country: Germany
facility: Research Site
city: Tübingen
country: Germany
facility: Research Site
city: Athens
country: Greece
facility: Research Site
city: Loannina
country: Greece
facility: Research Site
city: Thessaloniki
country: Greece
facility: Research Site
city: Haifa
country: Israel
facility: Research Site
city: Kfar-Saba
country: Israel
facility: Research Site
city: Petah Tiqva
country: Israel
facility: Research Site
city: Rehovot
country: Israel
facility: Research Site
city: Tel-Aviv
country: Israel
facility: Research Site
city: Tel-Hashomer
country: Israel
facility: Research Site
city: Brescia
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Padova
country: Italy
facility: Research Site
city: Pavia
country: Italy
facility: Research Site
city: Rome
country: Italy
facility: Research Site
city: Torino
country: Italy
facility: Research Site
city: Bialystok
country: Poland
facility: Research Site
city: Krakow
country: Poland
facility: Research Site
city: Lublin
country: Poland
facility: Research Site
city: Opole
country: Poland
facility: Research Site
city: Poznan
country: Poland
facility: Research Site
city: Szczecin
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Lisbon
country: Portugal
facility: Research Site
city: Santa Maira da Feira
country: Portugal
facility: Research Site
city: Alba Iulia
country: Romania
facility: Research Site
city: Bucurest
country: Romania
facility: Research Site
city: Onesti
country: Romania
facility: Research Site
city: Oradea
country: Romania
facility: Research Site
city: Timisoara
country: Romania
facility: Research Site
city: Kazan
country: Russian Federation
facility: Research Site
city: Krasnodar
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Obninsk
country: Russian Federation
facility: Research Site
city: Samara
country: Russian Federation
facility: Research Site
city: St. Petersburg
country: Russian Federation
facility: Research Site
city: Bilbao
country: Spain
facility: Research Site
city: Burgos
country: Spain
facility: Research Site
city: Girona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Malaga
country: Spain
facility: Research Site
city: Orense
country: Spain
facility: Research Site
city: Reus
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Dnepropetrovsk
country: Ukraine
facility: Research Site
city: Kharkov
country: Ukraine
facility: Research Site
city: Kiev
country: Ukraine
facility: Research Site
city: Lviv
country: Ukraine
facility: Research Site
city: Simferopol
country: Ukraine
facility: Research Site
city: Vinnitsa
country: Ukraine
facility: Research Site
Study officials:
affiliation: Klinik für Onkologie, Hämatologie und Knochenmarktransplantationen Universitätsklinikum Hamburg-Eppendorf, Germany
name: Bokemeyer, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bokemeyer C, Bondarenko I, Makhson A, Hartmann JT, Aparicio J, de Braud F, Donea S, Ludwig H, Schuch G, Stroh C, Loos AH, Zubel A, Koralewski P. Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J Clin Oncol. 2009 Feb 10;27(5):663-71. doi: 10.1200/JCO.2008.20.8397. Epub 2008 Dec 29.
citation: Bokemeyer C, Bondarenko I, Hartmann JT, de Braud F, Schuch G, Zubel A, Celik I, Schlichting M, Koralewski P. Efficacy according to biomarker status of cetuximab plus FOLFOX-4 as first-line treatment for metastatic colorectal cancer: the OPUS study. Ann Oncol. 2011 Jul;22(7):1535-1546. doi: 10.1093/annonc/mdq632. Epub 2011 Jan 12.