A Histopathologic and Imaging Study of Renal Cell Carcinoma Vasculature in the Setting of Sunitinib Therapy Prior to Cytoreductive Nephrectomy
- To correlate histologic measures of tumor angiogenesis and VHL mutation/methylation
status with clinical outcome in patients with stage IV renal cell carcinoma treated
with sunitinib malate.
- To determine the effects of sunitinib malate on tumor vascular permeability by dynamic
contrast-enhanced MRI and iodine I 124 chimeric monoclonal antibody G250 positron
emission tomography (PET) after 2 weeks of therapy.
- To correlate steady-state plasma concentrations of sunitinib malate and angiogenic
growth factors in serum with clinical outcome in these patients.
- Neoadjuvant therapy:Patients receive oral sunitinib malate once daily on days 1-14.
- Cytoreductive surgery: Patients undergo cytoreductive nephrectomy on day 16.
- Adjuvant therapy:Beginning at least 4 weeks after surgery, patients receive oral
sunitinib malate once daily on days 1-28. Treatment repeats every 42 days in the
absence of disease progression or unacceptable toxicity.
Patients undergo dynamic contrast-enhanced MRI with motexafin gadolinium and positron
emission tomography with iodine I 124 chimeric monoclonal antibody G250 at baseline and
after completion of neoadjuvant sunitinib malate (prior to cytoreductive nephrectomy).
Patients undergo tumor tissue and blood sample collection periodically for correlative
laboratory studies. Tumor tissue samples are analyzed for VHL mutations and other somatic
genetic mutations by mutation analysis; allelic loss or gain by comparative genomic
amplification; microvessel density (MVD) by immunohistochemical staining for CD34 and CD105;
pERK, SMA, Ki-67, HIF-1α, CAIX, macrophage migration inhibition factor (MIF), and CREB by
multicolor analysis; and VEGF-R1 and -R2 and other relevant antigen expression by validated
assays. Blood samples are analyzed for pharmacokinetics; angiogenic growth factor levels
(e.g., free VEGF, basic FGF, and other markers); and polymorphisms in VEGF, VEGFR, VHL, and
After completion of study treatment, patients are followed periodically.
Primary Purpose: Treatment
Keith T. Flaherty, MD
Abramson Cancer Center of the University of Pennsylvania
|Abramson Cancer Center of the University of Pennsylvania||Philadelphia, Pennsylvania 19104-4283|