NCT00717587

Sunitinib Before and After Surgery in Treating Patients With Stage IV Kidney Cancer

A Histopathologic and Imaging Study of Renal Cell Carcinoma Vasculature in the Setting of Sunitinib Therapy Prior to Cytoreductive Nephrectomy

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: Abramson Cancer Center at Penn Medicine · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

RATIONALE: Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving sunitinib before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving it after surgery may kill any tumor cells that remain after surgery. PURPOSE: This phase II trial is studying how well sunitinib works when given before and after surgery in treating patients with stage IV kidney cancer.

Detailed description

OBJECTIVES: * 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. OUTLINE: * 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 HIF. After completion of study treatment, patients are followed periodically.

Conditions

• Kidney Cancer

Interventions

Type	Name	Description
DRUG	motexafin gadolinium
DRUG	sunitinib malate
GENETIC	comparative genomic hybridization
GENETIC	gene expression analysis
GENETIC	mutation analysis
GENETIC	polymorphism analysis
OTHER	immunohistochemistry staining method
OTHER	iodine I-124 girentuximab
OTHER	laboratory biomarker analysis
OTHER	pharmacological study
PROCEDURE	adjuvant therapy
PROCEDURE	neoadjuvant therapy
PROCEDURE	therapeutic conventional surgery

Timeline

• Start date: 2008-06-01
• Primary completion: 2010-07-01
• First posted: 2008-07-17
• Last updated: 2014-01-10

Locations

1 site across 1 country: United States