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

Primary Purpose

Neoplasm Metastasis, Colorectal Cancer

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Cetuximab
Oxaliplatin
Sponsored by
Merck KGaA, Darmstadt, Germany
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neoplasm Metastasis focused on measuring FOLFOX-4, Cetuximab, First-line mCRC, EGFR positive, metastatic CRC

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

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Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Cetuximab Plus FOLFOX-4

FOLFOX-4 Alone

Arm Description

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.
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.
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.
Participants With No Residual Tumor After Metastatic Surgery
No residual tumor after on-study surgery for metastases.
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).
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.
Safety - Number of Patients Experiencing Any Adverse Event
Please refer to Adverse Events section for further details

Full Information

First Posted
July 28, 2005
Last Updated
August 5, 2014
Sponsor
Merck KGaA, Darmstadt, Germany
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1. Study Identification

Unique Protocol Identification Number
NCT00125034
Brief Title
Oxaliplatin and Cetuximab in First-line Treatment of Metastatic Colorectal Cancer (mCRC)
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2011
Overall Recruitment Status
Completed
Study Start Date
July 2005 (undefined)
Primary Completion Date
March 2007 (Actual)
Study Completion Date
November 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck KGaA, Darmstadt, Germany

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neoplasm Metastasis, Colorectal Cancer
Keywords
FOLFOX-4, Cetuximab, First-line mCRC, EGFR positive, metastatic CRC

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
344 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cetuximab Plus FOLFOX-4
Arm Type
Experimental
Arm Title
FOLFOX-4 Alone
Arm Type
Active Comparator
Intervention Type
Biological
Intervention Name(s)
Cetuximab
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Intervention Description
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
Primary Outcome Measure Information:
Title
Best Overall Response Rate - Independent Review Committee (IRC)
Description
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.
Time Frame
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 Outcome Measure Information:
Title
Best Overall Response Rate (Chinese V-Ki-ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) Wild-Type Population)
Description
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.
Time Frame
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
Title
Best Overall Response Rate (KRAS Mutant Population)
Description
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.
Time Frame
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
Title
Progression-free Survival Time
Description
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 Frame
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
Title
Progression-free Survival Time (KRAS Wild-Type Population)
Description
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 Frame
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
Title
Progression-free Survival Time (KRAS Mutant Population)
Description
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 Frame
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
Title
Overall Survival Time
Description
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 Frame
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
Title
Overall Survival Time (KRAS Wild-Type Population)
Description
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 Frame
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
Title
Overall Survival Time (KRAS Mutant Population)
Description
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 Frame
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
Title
Participants With No Residual Tumor After Metastatic Surgery
Description
No residual tumor after on-study surgery for metastases.
Time Frame
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
Title
Disease Control Rate (Cut Off Date 4 August 2006)
Description
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).
Time Frame
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
Title
Duration of Response
Description
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 Frame
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
Title
Safety - Number of Patients Experiencing Any Adverse Event
Description
Please refer to Adverse Events section for further details
Time Frame
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bokemeyer, Prof. Dr.
Organizational Affiliation
Klinik für Onkologie, Hämatologie und Knochenmarktransplantationen Universitätsklinikum Hamburg-Eppendorf, Germany
Official's Role
Principal Investigator
Facility Information:
Facility Name
Research Site
City
Graz
Country
Austria
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Linz
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Austria
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Salzburg
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Austria
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Wien
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Austria
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Zams
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Austria
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Antwerpen
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Belgium
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Bonheiden
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Belgium
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Brugge
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Belgium
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Hasselt
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Belgium
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Leuven
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Belgium
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Roeselare
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Belgium
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Turnhout
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Belgium
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ZU Gent
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Belgium
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Besancon
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France
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Clermond Ferrand
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France
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Clichy
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France
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Montpellier
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France
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Paris
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France
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Rouen
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France
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Strasbourg
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France
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Aschaffenburg
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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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Hamburg
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Germany
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Kiel
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Germany
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Magdeburg
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Germany
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Mannheim
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Germany
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Nürnberg
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Germany
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Tübingen
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Germany
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Athens
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Greece
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Loannina
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Greece
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Thessaloniki
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Greece
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Haifa
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Israel
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Kfar-Saba
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Israel
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Petah Tiqva
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Israel
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Rehovot
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Israel
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Tel-Aviv
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Israel
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Tel-Hashomer
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Israel
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Brescia
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Italy
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Milano
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Italy
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Padova
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Italy
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Pavia
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Italy
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Rome
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Italy
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Torino
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Italy
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Bialystok
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Poland
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Krakow
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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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Poznan
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Poland
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Szczecin
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Poland
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Warszawa
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Poland
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Lisbon
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Portugal
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Santa Maira da Feira
Country
Portugal
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Alba Iulia
Country
Romania
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Bucurest
Country
Romania
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Onesti
Country
Romania
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Oradea
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Romania
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Timisoara
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Romania
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Kazan
Country
Russian Federation
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Krasnodar
Country
Russian Federation
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Moscow
Country
Russian Federation
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Obninsk
Country
Russian Federation
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Samara
Country
Russian Federation
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St. Petersburg
Country
Russian Federation
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Bilbao
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Spain
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Burgos
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Spain
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Girona
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Spain
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Madrid
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Spain
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Malaga
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Spain
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Orense
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Spain
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Reus
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Spain
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Valencia
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Spain
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Dnepropetrovsk
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Ukraine
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Kharkov
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Ukraine
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Kiev
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Ukraine
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Lviv
Country
Ukraine
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Simferopol
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Ukraine
Facility Name
Research Site
City
Vinnitsa
Country
Ukraine

12. IPD Sharing Statement

Citations:
PubMed Identifier
19114683
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.
Results Reference
result
PubMed Identifier
21228335
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.
Results Reference
result

Learn more about this trial

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

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