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
18 Years
N/A
Both
Stage IV Colorectal Cancer
Trial Information
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
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.
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
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Dose limiting toxicity.
Outcome Time Frame:
6 weeks
Safety Issue:
Yes
Principal Investigator
Ulrich Hacker, PD Dr.
Investigator Role:
Principal Investigator
Investigator Affiliation:
University Cologne
Authority:
Germany: Federal Institute for Drugs and Medical Devices
Study ID:
AIO KRK 0205
NCT ID:
NCT00784446
Start Date:
April 2008
Completion Date:
December 2012
Related Keywords:
- Stage IV Colorectal Cancer
- AIO
- colorectal cancer
- 0205
- Capecitabine
- Oxaliplatin
- Bevacizumab
- Imatinib
- Colorectal Neoplasms
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