Oxaliplatin and Cetuximab in First-line Treatment of Metastatic Colorectal Cancer (mCRC)

Colorectal Cancer Clinical Trial

— OPUS  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00125034
• Other study ID #: EMR 62202-047
• Status: Completed
• Phase: Phase 2
• First received: July 28, 2005
• Last updated: August 5, 2014
• Start date: July 2005
• Est. completion date: November 2010

Study information

• Verified date: August 2011
• Source: Merck KGaA
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 344
• Est. completion date: November 2010
• Est. primary completion date: March 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms
• Neoplasm Metastasis

Intervention

Biological:
• Cetuximab
Cetuximab will always be administered first, followed by oxaliplatin at least 1 hour later. Following completion of the oxaliplatin infusion or simultaneously with oxaliplatin folinic acid (FA) will be administered (at a dose of 200 mg/m^2, infused over 120 minutes, on day 1 and day 2, every two weeks) and then 5-Fluorouracil (5-FU) (as a bolus of 400 mg/m^2/day intravenously (IV) over 2-4 minutes followed by 600 mg/m^2/day infused over 22-hour, on day 1 and day 2, every two weeks). Until progression or unacceptable toxicity develops

Drug:
• Oxaliplatin
Oxaliplatin will always be administered first or simultaneously with FA (at a dose of 200 mg/m^2, infused over 120 minutes, on day 1 and day 2, every two weeks) and then 5-FU (as a bolus of 400 mg/m^2/day IV over 2-4 minutes followed by 600 mg/m^2/day infused over 22-hour, on day 1 and day 2, every two weeks). Until progression or unacceptable toxicity develops

Locations

Country	Name	City	State
Austria	Research Site	Graz
Austria	Research Site	Linz
Austria	Research Site	Salzburg
Austria	Research Site	Wien
Austria	Research Site	Zams
Belgium	Research Site	Antwerpen
Belgium	Research Site	Bonheiden
Belgium	Research Site	Brugge
Belgium	Research Site	Hasselt
Belgium	Research Site	Leuven
Belgium	Research Site	Roeselare
Belgium	Research Site	Turnhout
Belgium	Research Site	ZU Gent
France	Research Site	Besancon
France	Research Site	Clermond Ferrand
France	Research Site	Clichy
France	Research Site	Montpellier
France	Research Site	Paris
France	Research Site	Rouen
France	Research Site	Strasbourg
Germany	Research Site	Aschaffenburg
Germany	Research Site	Dresden
Germany	Research Site	Essen
Germany	Research Site	Hamburg
Germany	Research Site	Kiel
Germany	Research Site	Magdeburg
Germany	Research Site	Mannheim
Germany	Research Site	Nürnberg
Germany	Research Site	Tübingen
Greece	Research Site	Athens
Greece	Research Site	Loannina
Greece	Research Site	Thessaloniki
Israel	Research Site	Haifa
Israel	Research Site	Kfar-Saba
Israel	Research Site	Petah Tiqva
Israel	Research Site	Rehovot
Israel	Research Site	Tel-Aviv
Israel	Research Site	Tel-Hashomer
Italy	Research Site	Brescia
Italy	Research Site	Milano
Italy	Research Site	Padova
Italy	Research Site	Pavia
Italy	Research Site	Rome
Italy	Research Site	Torino
Poland	Research Site	Bialystok
Poland	Research Site	Krakow
Poland	Research Site	Lublin
Poland	Research Site	Opole
Poland	Research Site	Poznan
Poland	Research Site	Szczecin
Poland	Research Site	Warszawa
Portugal	Research Site	Lisbon
Portugal	Research Site	Santa Maira da Feira
Romania	Research Site	Alba Iulia
Romania	Research Site	Bucurest
Romania	Research Site	Onesti
Romania	Research Site	Oradea
Romania	Research Site	Timisoara
Russian Federation	Research Site	Kazan
Russian Federation	Research Site	Krasnodar
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Obninsk
Russian Federation	Research Site	Samara
Russian Federation	Research Site	St. Petersburg
Spain	Research Site	Bilbao
Spain	Research Site	Burgos
Spain	Research Site	Girona
Spain	Research Site	Madrid
Spain	Research Site	Malaga
Spain	Research Site	Orense
Spain	Research Site	Reus
Spain	Research Site	Valencia
Ukraine	Research Site	Dnepropetrovsk
Ukraine	Research Site	Kharkov
Ukraine	Research Site	Kiev
Ukraine	Research Site	Lviv
Ukraine	Research Site	Simferopol
Ukraine	Research Site	Vinnitsa

Sponsors (1)

Lead Sponsor	Collaborator
Merck KGaA

Countries where clinical trial is conducted

Austria,  Belgium,  France,  Germany,  Greece,  Israel,  Italy,  Poland,  Portugal,  Romania,  Russian Federation,  Spain,  Ukraine, 

References & Publications (2)

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 On — View 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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Best Overall Response Rate - Independent Review Committee (IRC)	The best overall response rate is defined as the percentage of subjects having achieved confirmed Complete Response + Partial Response as the best overall response according to radiological assessments (based on modified World Health Organisation (WHO) criteria) as assessed by an IRC.	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	No
Secondary	Best Overall Response Rate (Chinese V-Ki-ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) Wild-Type Population)	The best overall response rate is defined as the percentage of subjects having achieved confirmed Complete Response + Partial Response as the best overall response according to radiological assessments (based on modified WHO criteria) as assessed by an IRC.	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	No
Secondary	Best Overall Response Rate (KRAS Mutant Population)	The best overall response rate is defined as the percentage of subjects having achieved confirmed Complete Response + Partial Response as the best overall response according to radiological assessments (based on modified WHO criteria) as assessed by an IRC.	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	No
Secondary	Progression-free Survival Time	Duration from randomization until radiological progression as assessed by an IRC (based on modified WHO criteria) or death due to any cause.; Only deaths within 60 days of last tumor assessment are considered. Patients without event are censored on the date of last tumor assessment.	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	No
Secondary	Progression-free Survival Time (KRAS Wild-Type Population)	Duration from randomization until radiological progression as assessed by an IRC (based on modified WHO criteria) or death due to any cause.; Only deaths within 60 days of last tumor assessment are considered. Patients without event are censored on the date of last tumor assessment.	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	No
Secondary	Progression-free Survival Time (KRAS Mutant Population)	Duration from randomization until radiological progression as assessed by an IRC (based on modified WHO criteria) or death due to any cause.; Only deaths within 60 days of last tumor assessment are considered. Patients without event are censored on the date of last tumor assessment.	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	No
Secondary	Overall Survival Time	Time from randomization to death. Patients without event are censored at the last date known to be alive or at the clinical cut-off date, whatever is earlier.	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	No
Secondary	Overall Survival Time (KRAS Wild-Type Population)	Time from randomization to death. Patients without event are censored at the last date known to be alive or at the clinical cut-off date, whatever is earlier.	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	No
Secondary	Overall Survival Time (KRAS Mutant Population)	Time from randomization to death. Patients without event are censored at the last date known to be alive or at the clinical cut-off date, whatever is earlier.	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	No
Secondary	Participants With No Residual Tumor After Metastatic Surgery	No residual tumor after on-study surgery for metastases.	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	No
Secondary	Disease Control Rate (Cut Off Date 4 August 2006)	The disease control rate is defined as the percentage of subjects having achieved confirmed Complete Response + Partial Response + Stable Disease as best overall response according to radiological assessments as assessed by IRC (based on modified WHO criteria).	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	No
Secondary	Duration of Response	Time from first assessment of Complete Response or Partial Response to disease progression or death (within 60 days of last tumor assessment).; Patients without event are censored on the date of last tumor assessment. Tumor assessments based on modified WHO criteria.	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	No
Secondary	Safety - Number of Patients Experiencing Any Adverse Event	Please refer to Adverse Events section for further details	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	Yes