NCT00125034

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.

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
344

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Jul 2005

Longer than P75 for phase_2

Geographic Reach
13 countries

78 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 1, 2005

Completed
27 days until next milestone

First Submitted

Initial submission to the registry

July 28, 2005

Completed
1 day until next milestone

First Posted

Study publicly available on registry

July 29, 2005

Completed
1.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2007

Completed
3.7 years until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2010

Completed
11 months until next milestone

Results Posted

Study results publicly available

October 4, 2011

Completed
Last Updated

August 7, 2014

Status Verified

August 1, 2011

Enrollment Period

1.7 years

First QC Date

July 28, 2005

Results QC Date

August 23, 2011

Last Update Submit

August 5, 2014

Conditions

Keywords

FOLFOX-4CetuximabFirst-line mCRCEGFR positivemetastatic CRC

Outcome Measures

Primary Outcomes (1)

  • 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

Secondary Outcomes (12)

  • Best Overall Response Rate (Chinese V-Ki-ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) Wild-Type Population)

    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

  • Best Overall Response Rate (KRAS Mutant Population)

    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

  • Progression-free Survival Time

    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

  • Progression-free Survival Time (KRAS Wild-Type Population)

    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

  • Progression-free Survival Time (KRAS Mutant Population)

    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

  • +7 more secondary outcomes

Study Arms (2)

Cetuximab Plus FOLFOX-4

EXPERIMENTAL
Biological: Cetuximab

FOLFOX-4 Alone

ACTIVE COMPARATOR
Drug: Oxaliplatin

Interventions

CetuximabBIOLOGICAL

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

Cetuximab Plus FOLFOX-4

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

FOLFOX-4 Alone

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (78)

Research Site

Graz, Austria

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Linz, Austria

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Salzburg, Austria

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Vienna, Austria

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Zams, Austria

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Antwerp, Belgium

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Bonheiden, Belgium

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Bruges, Belgium

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Hasselt, Belgium

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Leuven, Belgium

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Roeselare, Belgium

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Turnhout, Belgium

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ZU Gent, Belgium

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Besançon, France

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Clermond Ferrand, France

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Clichy, France

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Montpellier, France

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Paris, France

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Rouen, France

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Strasbourg, France

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Aschaffenburg, Germany

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Dresden, Germany

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Essen, Germany

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Hamburg, Germany

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Kiel, Germany

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Magdeburg, Germany

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Mannheim, Germany

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Nuremberg, Germany

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Tübingen, Germany

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Athens, Greece

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Loannina, Greece

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Thessaloniki, Greece

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Haifa, Israel

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Kfar Saba, Israel

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Petah Tikva, Israel

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Rehovot, Israel

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Tel Aviv, Israel

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Tel Litwinsky, Israel

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Brescia, Italy

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Milan, Italy

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Padua, Italy

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Pavia, Italy

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Rome, Italy

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Torino, Italy

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Bialystok, Poland

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Krakow, Poland

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Lublin, Poland

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Opole, Poland

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Poznan, Poland

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Szczecin, Poland

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Warsaw, Poland

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Lisbon, Portugal

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Santa Maira Da Feira, Portugal

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Alba Iulia, Romania

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Bucurest, Romania

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Onești, Romania

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Oradea, Romania

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Timișoara, Romania

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Kazan', Russia

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Krasnodar, Russia

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Moscow, Russia

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Obninsk, Russia

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Saint Petersburg, Russia

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Samara, Russia

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Bilbao, Spain

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Burgos, Spain

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Girona, Spain

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Madrid, Spain

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Málaga, Spain

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Ourense, Spain

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Reus, Spain

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Valencia, Spain

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Dnipro, Ukraine

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Kharkiv, Ukraine

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Kiev, Ukraine

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Lviv, Ukraine

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Simferopol, Ukraine

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Vinnitsa, Ukraine

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Related Publications (2)

  • 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.

  • 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.

MeSH Terms

Conditions

Neoplasm MetastasisColorectal Neoplasms

Interventions

CetuximabOxaliplatin

Condition Hierarchy (Ancestors)

Neoplastic ProcessesNeoplasmsPathologic ProcessesPathological Conditions, Signs and SymptomsIntestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteDigestive System DiseasesGastrointestinal DiseasesColonic DiseasesIntestinal DiseasesRectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsCoordination ComplexesOrganic Chemicals

Limitations and Caveats

A non-specific outcome measure 'Safety' was deleted from this entry in error. A replacement outcome has been created. The 'Safety' outcome refers to adverse events and these are shown in the 'Adverse Events' section.

Results Point of Contact

Title
Inmaculada Ollero/Clinical Trial Manager
Organization
Merck Serono

Study Officials

  • Bokemeyer, Prof. Dr.

    Klinik für Onkologie, Hämatologie und Knochenmarktransplantationen Universitätsklinikum Hamburg-Eppendorf, Germany

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
GT60
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 28, 2005

First Posted

July 29, 2005

Study Start

July 1, 2005

Primary Completion

March 1, 2007

Study Completion

November 1, 2010

Last Updated

August 7, 2014

Results First Posted

October 4, 2011

Record last verified: 2011-08

Locations