A Phase II Study of the Combination of Aflibercept (VEGF-Trap) Plus Modified FOLFOX 6 in Patients With Previously Untreated Metastatic Colorectal Cancer
I. To evaluate the progression free survival (PFS) of patients with untreated metastatic
colorectal cancer (mCRC) receiving the combination of modified leucovorin calcium,
fluorouracil, oxaliplatin (FOLFOX6) (mFOLFOX6) and aflibercept.
I. To evaluate the objective response rate (complete response [CR] + partial response [PR])
and the disease control rate (CR + PR + stable disease [SD]), as determined by Response
Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria, of patients with untreated mCRC
receiving the combination of mFOLFOX6 and aflibercept.
II. To evaluate overall survival of patients with untreated mCRC receiving the combination
of mFOLFOX6 and aflibercept.
III. To further characterize the safety and toxicity of the combination of mFOLFOX6 and
aflibercept, including 60 day all-cause mortality.
IV. To describe patients with mCRC whose disease is rendered resectable as a consequence of
therapy with the combination of mFOLFOX 6 and aflibercept.
I. To assess the use of dynamic imaging modalities including dynamic contrast
enhanced-magnetic resonance imaging (DCE-MRI) and fluorodeoxyglucose (FDG)-positron emission
tomography (PET) to evaluate changes in vascular permeability and FDG avidity and correlate
with clinical efficacy (PFS, overall survival [OS], and response by RECIST 1.1).
II. To evaluate circulating levels of vascular endothelial growth factor A (VEGFA),
phosphatidylinositol glycan anchor biosynthesis, class F (PlGF), soluble vascular
endothelial growth factor receptor 2 (VEGF-R2), chemokine (C-X-C motif) ligand 12 (CXCL12)
and chemokine (C-X-C motif) receptor 4 (CXCR4) as potential biomarkers for efficacy of
III. To evaluate for the presence of VEGF single nucleotide polymorphisms (SNPs) and whether
any SNP(s), when detected, may be predictive of efficacy and/or toxicity of aflibercept.
IV. To assess microvessel density/tumor blood flow, capillary permeability and vessel
normalization by tumor biopsy pre and post treatment with aflibercept.
V. To evaluate the presence of hypertension as a predictive biomarker for clinical efficacy
Patients receive aflibercept intravenously (IV) over 1 hour followed by oxaliplatin IV over
2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV over 5-15 minutes and then
continuously over 46 hours on days 1 and 15. Courses repeat every 28 days in the absence of
disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 4 weeks.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Proportion of patients alive and progression-free
Assuming that the number of treatment successes (alive and progression-free) is binomially distributed, proportion estimates along with their corresponding exact 95% confidence intervals will be calculated.
At 15 months from initiation of therapy
Goldberg Richard, MD
Ohio State University Comprehensive Cancer Center
United States: Food and Drug Administration
|University of Michigan||Ann Arbor, Michigan 48109-0624|
|Roswell Park Cancer Institute||Buffalo, New York 14263|
|University of North Carolina||Chapel Hill, North Carolina 27599|
|Ohio State University Medical Center||Columbus, Ohio 43210|