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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT00125034
First received: July 28, 2005
Last updated: August 23, 2011
Last verified: August 2011
  Purpose

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.


Condition Intervention Phase
Neoplasm Metastasis
Colorectal Cancer
Biological: Cetuximab
Drug: Oxaliplatin
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • Best Overall Response Rate - Independent Review Committee (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 ] [ Designated as safety issue: No ]
    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) [ 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 ] [ Designated as safety issue: No ]
    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) [ 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 ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]

    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) [ 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 ] [ Designated as safety issue: No ]

    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) [ 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 ] [ Designated as safety issue: No ]

    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 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 ] [ Designated as safety issue: No ]
    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 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 ] [ Designated as safety issue: No ]
    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 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 ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    No residual tumor after on-study surgery for metastases.

  • Disease Control Rate (Cut Off Date 4 August 2006) [ 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 ] [ Designated as safety issue: No ]
    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 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 ] [ Designated as safety issue: No ]

    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 [ 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 ] [ Designated as safety issue: Yes ]
    Please refer to Adverse Events section for further details


Enrollment: 344
Study Start Date: July 2005
Study Completion Date: November 2010
Primary Completion Date: March 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cetuximab Plus FOLFOX-4 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

Active Comparator: FOLFOX-4 Alone 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


  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00125034

  Show 78 Study Locations
Sponsors and Collaborators
Merck KGaA
Investigators
Principal Investigator: Bokemeyer, Prof. Dr. Klinik für Onkologie, Hämatologie und Knochenmarktransplantationen Universitätsklinikum Hamburg-Eppendorf, Germany
  More Information

Publications:
Responsible Party: Merck KGaA
ClinicalTrials.gov Identifier: NCT00125034     History of Changes
Other Study ID Numbers: EMR 62202-047
Study First Received: July 28, 2005
Results First Received: August 23, 2011
Last Updated: August 23, 2011
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Merck KGaA:
FOLFOX-4
Cetuximab
First-line mCRC
EGFR positive
metastatic CRC
first-line MCRC

Additional relevant MeSH terms:
Neoplasms
Colorectal Neoplasms
Neoplasm Metastasis
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neoplastic Processes
Pathologic Processes
Oxaliplatin
Cetuximab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 20, 2014