Cetuximab, Capecitabine, Oxaliplatin and Bevacizumab in Advanced Colorectal Cancer

This study has been completed.
Sponsor:
Collaborators:
Koningin Wilhelmina Fonds
Sanofi
Roche Pharma AG
Immunicon
Information provided by (Responsible Party):
Dutch Colorectal Cancer Group
ClinicalTrials.gov Identifier:
NCT00208546
First received: September 13, 2005
Last updated: February 1, 2012
Last verified: February 2012
  Purpose

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.


Condition Intervention Phase
Colorectal Cancer
Drug: 21Capecitabine + bevacizumab + oxaliplatin
Drug: 1Capecitabine + oxaliplatin + bevacizumab + cetuximab
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Cetuximab Added to Capecitabine, Oxaliplatin and Bevacizumab in Patients With Previously Untreated Advanced Colorectal Carcinoma, a Randomised Phase III Study

Resource links provided by NLM:


Further study details as provided by Dutch Colorectal Cancer Group:

Primary Outcome Measures:
  • progression free survival [ Time Frame: study duration ] [ Designated as safety issue: No ]
  • toxicity [ Time Frame: study duration ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • tumour response (complete response [CR], partial response [PR] or stable disease [SD]) [ Time Frame: study duration ] [ Designated as safety issue: No ]
  • response duration [ Time Frame: study duration ] [ Designated as safety issue: No ]
  • overall survival [ Time Frame: study duration ] [ Designated as safety issue: No ]
  • quality of life [ Time Frame: study duration ] [ Designated as safety issue: No ]
  • translational research [ Time Frame: study duration ] [ Designated as safety issue: No ]

Enrollment: 750
Study Start Date: June 2005
Study Completion Date: December 2009
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1Capecitabine + bevacizumab + oxaliplatin + cetuximab Drug: 1Capecitabine + oxaliplatin + bevacizumab + cetuximab
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).
Active Comparator: 21Capecitabine + bevacizumab + oxaliplatin Drug: 21Capecitabine + bevacizumab + oxaliplatin
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.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  • 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
  • Other malignancies in the past 5 years with the exception of adequately treated carcinoma in situ of the cervix or squamous or basal cell carcinoma of the skin
  • Concomitant treatments: concomitant (or within 4 weeks before randomisation) administration of any other experimental drug under investigation; concurrent treatment with any other anti-cancer therapy; full-dose anticoagulation
  • Continuous use of immunosuppressive agents
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00208546

Locations
Netherlands
University Medical Center Nijmegen
Nijmegen, Gelderland, Netherlands
Sponsors and Collaborators
Dutch Colorectal Cancer Group
Koningin Wilhelmina Fonds
Sanofi
Roche Pharma AG
Immunicon
Investigators
Principal Investigator: C JA Punt, MD PhD University Medical Centre Nijmegen
  More Information

Additional Information:
Publications:
Punt CJ et al. Randomized phase III study of capecitabine, oxaliplatin, and bevacizumab with or without cetuximab in advanced colorectal cancer (ACC), the CAIRO2 study of the Dutch Colorectal Cancer Group (DCCG. J Clin Oncol 26: 2008 (May 20 suppl; abstr LBA4011).

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Dutch Colorectal Cancer Group
ClinicalTrials.gov Identifier: NCT00208546     History of Changes
Other Study ID Numbers: CAIRO2
Study First Received: September 13, 2005
Last Updated: February 1, 2012
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Dutch Colorectal Cancer Group:
capecitabine
oxaliplatin
bevacizumab
cetuximab
advanced colorectal cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Oxaliplatin
Capecitabine
Bevacizumab
Cetuximab
Fluorouracil
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on April 22, 2014