Sunitinib Before and After Surgery in Treating Patients With Stage IV Kidney Cancer
Recruitment status was Recruiting
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.
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
|Study Design:||Primary Purpose: Treatment|
|Official Title:||A Histopathologic and Imaging Study of Renal Cell Carcinoma Vasculature in the Setting of Sunitinib Therapy Prior to Cytoreductive Nephrectomy|
- Progression-free survival [ Designated as safety issue: No ]
- Tumor regression as assessed by RECIST criteria [ Designated as safety issue: No ]
|Study Start Date:||June 2008|
|Estimated Primary Completion Date:||July 2010 (Final data collection date for primary outcome measure)|
- 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 HIF.
After completion of study treatment, patients are followed periodically.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00717587
|United States, Pennsylvania|
|Abramson Cancer Center of the University of Pennsylvania||Recruiting|
|Philadelphia, Pennsylvania, United States, 19104-4283|
|Contact: Clinical Trials Office - Abramson Cancer Center of the Univers 800-474-9892|
|Principal Investigator:||Keith T. Flaherty, MD||Abramson Cancer Center of the University of Pennsylvania|