NCT00208546

Brief Summary

This is a study to assess the efficacy and safety of the addition of cetuximab to the combined regimen of capecitabine, oxaliplatin and bevacizumab in patients with previously untreated advanced colorectal carcinoma. It is an open, comparative study, comparing the effects of capecitabine, oxaliplatin and bevacizumab to those of the same regimen plus cetuximab. Seven hundred fifty patients will be included. Treatment will continue until disease progression or serious toxicity and follow up will continue until death. It is anticipated that the addition of cetuximab will lead to an increase in progression free survival.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
750

participants targeted

Target at P50-P75 for phase_3 colorectal-cancer

Timeline
Completed

Started Jun 2005

Geographic Reach
1 country

1 active site

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

June 1, 2005

Completed
3 months until next milestone

First Submitted

Initial submission to the registry

September 13, 2005

Completed
8 days until next milestone

First Posted

Study publicly available on registry

September 21, 2005

Completed
3.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2009

Completed
5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2009

Completed
Last Updated

February 2, 2012

Status Verified

February 1, 2012

Enrollment Period

4.1 years

First QC Date

September 13, 2005

Last Update Submit

February 1, 2012

Conditions

Colorectal Cancer

Keywords

capecitabineoxaliplatinbevacizumabcetuximabadvanced colorectal cancer

Outcome Measures

Primary Outcomes (2)

  • progression free survival

    study duration

  • toxicity

    study duration

Secondary Outcomes (5)

  • tumour response (complete response [CR], partial response [PR] or stable disease [SD])

    study duration

  • response duration

    study duration

  • overall survival

    study duration

  • quality of life

    study duration

  • translational research

    study duration

Study Arms (2)

1Capecitabine + bevacizumab + oxaliplatin + cetuximab

EXPERIMENTAL
Drug: 1Capecitabine + oxaliplatin + bevacizumab + cetuximab

21Capecitabine + bevacizumab + oxaliplatin

ACTIVE COMPARATOR
Drug: 21Capecitabine + bevacizumab + oxaliplatin

Interventions

21Capecitabine + bevacizumab + oxaliplatinDRUG

3-weekly cycles: Ca 1000 mg/m2 orally day 1-14, O 130 mg/m2 i.v. day 1 (6 cycles), B 7,5 mg/kg i.v. day 1.

21Capecitabine + bevacizumab + oxaliplatin
1Capecitabine + oxaliplatin + bevacizumab + cetuximabDRUG

3-weekly cycles: Ca 1000 mg/m2 orally day 1-14, O 130 mg/m2 i.v. day 1 (6 cycles), B 7,5 mg/kg i.v. day 1, Ce 250 mg/m2 i.v. day 1, 8, 15 (day 1 cycle 1: 400 mg/m2).

1Capecitabine + bevacizumab + oxaliplatin + cetuximab

Eligibility Criteria

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

You may qualify if:

  • Histology and Staging Disease
  • Histologically proven advanced colorectal cancer (CRC); not amenable to curative surgery
  • Of Note: In case of a single metastasis, histological or cytological proof of colorectal carcinoma should be obtained prior to randomisation.
  • Unidimensionally measurable disease (\>= 1 cm on spiral CT scan or \>= 2 cm on chest X-ray; liver ultrasound not allowed). Index lesions should not be in a previously irradiated area. Serum carcinoembryonic antigen (CEA) may not be used as a parameter for disease evaluation.
  • In case of previous radiotherapy, at least one measurable lesion should be located outside the irradiated field.
  • General Conditions
  • Signed written informed consent
  • Age 18 years and above
  • World Health Organization (WHO) performance status 0-1
  • Adequate bone marrow function (white blood cell count \[WBC\] \> 3.0 x 10\^9/L, platelets \> 100 x 10\^9/L, hemoglobin \[Hb\] \> 6 mmol/L)
  • Adequate hepatic function: total bilirubin \< 2 x upper normal limit, aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) \< 3 x upper normal limits (in case of liver metastases \< 5 x upper normal limits)
  • Adequate renal function: serum creatinine \< 1.5 x upper normal limit
  • Urinary protein excretion \< 0.5 gram/24h
  • Expected adequacy of follow-up

You may not qualify if:

  • Prior chemotherapy for advanced disease; prior adjuvant chemotherapy is allowed provided that the last administration was given \> 6 months prior to randomisation, and that patients have recovered from all toxic events related to adjuvant chemotherapy, and that safety evaluations during adjuvant chemotherapy do not present any risk for serious adverse events during the administration of protocol treatment.
  • Previous radiotherapy for rectal cancer or for symptomatic treatment of distant metastases is allowed, provided that at least one measurable lesion is located outside the irradiated field, irradiation has been completed for at least 4 weeks, and patients have recovered from all side effects.
  • Previous epidermal growth factor receptor (EGFR) targeting therapy
  • Sensory neuropathy \> grade 1
  • Bleeding diathesis or coagulation disorders or the need for full-dose anticoagulation
  • Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to the start of drug administration
  • Anticipated major surgical procedure during the course of the study
  • Serious non-healing wound or ulcer
  • Any condition preventing the intake or absorption of oral drugs
  • Significant cardiovascular disease (unstable angina pectoris, recent myocardial infarction \< 12 months, uncontrolled hypertension, previous cerebrovascular disease)
  • Pregnancy or lactation
  • Patients (males/females) with reproductive potential not implementing adequate contraceptive measures
  • Central nervous system metastases (in asymptomatic patients no screening is required)
  • Serious active infections
  • Other serious concomitant diseases preventing the safe administration of study drugs or likely to interfere with the study assessments
  • +3 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University Medical Center Nijmegen

Nijmegen, Gelderland, Netherlands

Location

Related Publications (5)

  • Tol J, Koopman M, Rodenburg CJ, Cats A, Creemers GJ, Schrama JG, Erdkamp FL, Vos AH, Mol L, Antonini NF, Punt CJ. A randomised phase III study on capecitabine, oxaliplatin and bevacizumab with or without cetuximab in first-line advanced colorectal cancer, the CAIRO2 study of the Dutch Colorectal Cancer Group (DCCG). An interim analysis of toxicity. Ann Oncol. 2008 Apr;19(4):734-8. doi: 10.1093/annonc/mdm607. Epub 2008 Feb 13.

    PMID: 18272912RESULT

  • Tol J, Koopman M, Cats A, Rodenburg CJ, Creemers GJ, Schrama JG, Erdkamp FL, Vos AH, van Groeningen CJ, Sinnige HA, Richel DJ, Voest EE, Dijkstra JR, Vink-Borger ME, Antonini NF, Mol L, van Krieken JH, Dalesio O, Punt CJ. Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. N Engl J Med. 2009 Feb 5;360(6):563-72. doi: 10.1056/NEJMoa0808268.

    PMID: 19196673RESULT

  • Baas J, Krens L, Bohringer S, Mol L, Punt C, Guchelaar HJ, Gelderblom H. Genome wide association study to identify predictors for severe skin toxicity in colorectal cancer patients treated with cetuximab. PLoS One. 2018 Dec 17;13(12):e0208080. doi: 10.1371/journal.pone.0208080. eCollection 2018.

    PMID: 30557370DERIVED

  • van Kessel CS, Samim M, Koopman M, van den Bosch MA, Borel Rinkes IH, Punt CJ, van Hillegersberg R. Radiological heterogeneity in response to chemotherapy is associated with poor survival in patients with colorectal liver metastases. Eur J Cancer. 2013 Jul;49(11):2486-93. doi: 10.1016/j.ejca.2013.03.027. Epub 2013 May 18.

    PMID: 23692811DERIVED

  • Simkens LH, Koopman M, Mol L, Veldhuis GJ, Ten Bokkel Huinink D, Muller EW, Derleyn VA, Teerenstra S, Punt CJ. Influence of body mass index on outcome in advanced colorectal cancer patients receiving chemotherapy with or without targeted therapy. Eur J Cancer. 2011 Nov;47(17):2560-7. doi: 10.1016/j.ejca.2011.06.038. Epub 2011 Jul 29.

    PMID: 21803570DERIVED

Related Links

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

BevacizumabOxaliplatinCetuximab

Condition Hierarchy (Ancestors)

Intestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsDigestive System DiseasesGastrointestinal DiseasesColonic DiseasesIntestinal DiseasesRectal Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

  • C JA Punt, MD PhD

    University Medical Centre Nijmegen

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 13, 2005

First Posted

September 21, 2005

Study Start

June 1, 2005

Primary Completion

July 1, 2009

Study Completion

December 1, 2009

Last Updated

February 2, 2012

Record last verified: 2012-02

Locations

NL(1)