A Phase II/Pharmacodynamic Study of Preoperative or Definitive FOLFOX Plus Bevacizumab, With the Additional Pharmacodynamic Goal of Assessing Tumor Blood Flow as Measured by Dynamic Contrast-enhanced MRI, and the Induction of Hypoxia and Apoptosis as Measured by PET in Patients With Rectal Cancer
The primary objectives of this study will determine the following: the response rate
(including pathological CR rate), TTP, and complications of treatment in patients with
rectal cancer treated with FOLFOX bevacizumab, the alteration of tumor blood flow (assessed
by DCE-MRI as percentage change in Ktrans) after 1 cycle of bevacizumab therapy compared to
baseline value in patients treated with FOLFOX alone and those treated with bevacizumab at 5
mg/kg., the degree of hypoxis (measured by tumor uptake of the 2-nitroimidazole EF5) induced
by bevacizumab treatment and its relationship to changes in tumor blood flow, and the degree
of apoptosis (measured by tumor uptake of di-annexin V) induced by bevacizumab treatment and
its relationship to changes in tumor blood flow. The secondary objectives of this study is
to determine in an exploratory fashion the relationship between tumor blood flow, hypoxia
induction, and apoptosis induction , and time to progression in patients continuing on to
receive Bevacizumab 5 mg/kg, to analyze archival tumor from the patients treated in this
trial for mutations in the MKK7 and SEK1 genes, and by semi-quantitative IHC for these and
other relevant proteins, to determine the relationship between vascular proliferation as
measured by DCE-MRI and markers of endothelial cell proliferation, and to obtain pilot data
on whether assays that measure vascular endothelial cell mitogenic stimulation and mitogenic
activity may predict response to therapy, time to progression and overall survival in
patients receiving bevacizumab 5 mg/kg.
Interventional
Primary Purpose: Treatment
Pathologic Complete Response (pCR)
Yes
Peter O'Dwyer, MD
Principal Investigator
Abramson Cancer Center of the University of Pennsylvania
United States: Food and Drug Administration
UPCC 05209
NCT01426074
August 2011
August 2014
Name | Location |
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Abramson Cancer Center of the University of Pennsylvania | Philadelphia, Pennsylvania 19104-4283 |