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First-line Therapy of Stage IV Colorectal Cancer

This study has been completed.
Sponsor:
Collaborators:
Roche Pharma AG
Novartis
Sanofi
Information provided by (Responsible Party):
Ulrich Hacker, University of Cologne
ClinicalTrials.gov Identifier:
NCT00784446
First received: November 3, 2008
Last updated: January 4, 2013
Last verified: January 2013

November 3, 2008
January 4, 2013
April 2008
August 2010   (final data collection date for primary outcome measure)
Dose limiting toxicity. [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT00784446 on ClinicalTrials.gov Archive Site
Assessment of overall response rate and progression free survival. [ Time Frame: 6 month ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
First-line Therapy of Stage IV Colorectal Cancer
A Phase I/II Study of Capecitabine/Oxaliplatin (XELOX) in Combination With Bevacizumab and Imatinib as First-line Treatment of Patients With Stage IV Colorectal Cancer

Assessment of safety and toxicity, definition of the dose limiting toxicity (DLT) of the combination therapy consisting of Capecitabine, Oxaliplatin, Bevacizumab and Imatinib.

The monoclonal anti-VEGF antibody bevacizumab has been approved for the treatment of stage IV colorectal cancer. The tyrosine kinase inhibitor imatinib mesylate has been shown to efficiently target PDGF-signalling. Blocking PDGFR-signalling leads to disruption of pericytes from the endothelium and reverses the maturation status thereby enhancing the sensitivity to anti-VEGF therapy.This background forms a rationale for a combined therapeutic PDGF and VEGF inhibition. Since bevacizumab shows best activity when used in combination with chemotherapy, capecitabine and oxaliplatin are included in this protocol. Patients with stage IV colorectal cancer and no prior chemotherapy can enter the study. Patients receive oral imatinib once a day on days 1-21. Oral Capecitabine is given on days 1-14 bid, Oxaliplatin and Bevacizumab are given on day 1. Courses are repeated every 22 days in the absence of disease progression or unacceptable toxicity.

Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Stage IV Colorectal Cancer
Drug: Oxaliplatin, Capecitabine, Bevacizumab, Imatinib

Dose level I:

Bevacizumab day 1: 7,5 mg/kg body weight Oxaliplatin day 1: 100 mg/m2 Capecitabine days 1-14 bid: 800 mg/m2 Imatinib days 1-21: 300 mg

Repeat on day 22.

Dose level II:

Bevacizumab day 1: 7,5 mg/kg body weight Oxaliplatin day 1: 130 mg/m2 Capecitabine days 1-14 bid: 1000 mg/m2 Imatinib days 1-21: 300 mg

Repeat on day 22.

Other Names:
  • Xeloda
  • Avastin
  • Imatinib
  • Eloxatin
No Intervention: XELOX, Bevacizumab, Imatinib
Intervention: Drug: Oxaliplatin, Capecitabine, Bevacizumab, Imatinib
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
51
December 2012
August 2010   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Histologically proven inoperable colorectal cancer
  • Adult patients >= 18 years of age
  • ECOG <2

Exclusion Criteria:

  • Preceding chemo- or immunotherapy with the exception of adjuvant or neoadjuvant treatment of non-metastatic disease ending ≥ 6 month prior to study inclusion. Progression within 6 month after the end of adjuvant therapy must be excluded.
  • Other malignancies with the exception of basal cell carcinoma or successfully treated carcinoma in situ of the cervix uteri.
  • No history of severe comorbidities, i. e. uncontrolled hypertension, GI-bleeding, congestive heart-failure NYHA class II-IV, symptomatic coronary heart disease, myocardial infarction within 1 year prior to study inclusion, serious cardiac arrhythmias requiring medication, Grade II or greater peripheral vascular disease and other severe uncontrolled co-morbidities
  • No history of stroke or other CNS-diseases (tumors, seizure, transient ischemic attack etc.)
  • ≥ Grade II peripheral artery vascular occlusive disease
  • Preexisting neuropathy ≥ Grade 1
  • Interstitial pneumonia or lung fibrosis
  • Serious, nonhealing wound, ulcer, or bone fracture
  • Preceding irradiation an indicator lesion except for documented progressive disease during irradiation and termination of irradiation ≥ 4 weeks from study inclusion
  • Thromboembolic or bleeding events within the last 6 month
  • Need for therapeutic anticoagulation (heparin, cumarin)
  • Use of ASS > 325 mg/die or NSAR
  • Proteinuria > 1+ (stix) as long as urine protein >1g/24h
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Germany
 
NCT00784446
AIO KRK 0205, ML20344
Yes
Ulrich Hacker, University of Cologne
University of Cologne
  • Roche Pharma AG
  • Novartis
  • Sanofi
Principal Investigator: Ulrich Hacker, PD Dr. University Cologne
University of Cologne
January 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP