Trial Information

The Role of VEGF-A Signaling in Maintenance of the Glomerular Filtration Barrier and Blood Pressure

OBJECTIVES:

I. To study the renal and blood pressure changes in patients treated with bevacizumab,
aflibercept, sunitinib malate, or cediranib for their cancer.

II. To determine the physiological mechanisms behind proteinuria and hypertension induced by
antiangiogenic therapies (i.e., rarefaction; imbalance in eNOS, prostacyclin [PGI_2],
prostaglandin E2 [PGE_2], and thromboxane A2 [TXA2]; renin/aldosterone; or renovascular
hypertension).

III. To determine whether soluble factors (like tyrosine kinase 1 [sFlt1], bFGF, and VEGF)
and steady state drug concentration are predictive of the development of
proteinuria/hypertension.

OUTLINE: This is a multicenter study.

Patients undergo blood and urine sample collection periodically. Urine samples are assessed
for PGI2 and TXA2 levels using validated ELISA methods. Urine is also assessed for protein
and creatinine levels, microalbumin, osmolality, and electrolytes. Blood samples are
assessed for pharmacokinetics and sFlt1, VEGF, and bFGF levels by validated ELISA methods.
Blood samples are also assessed for steady state drug concentration, renin, and aldosterone
levels.