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.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Dose limiting toxicity.
Ulrich Hacker, PD Dr.
Germany: Federal Institute for Drugs and Medical Devices
AIO KRK 0205