A Pilot Neoadjuvant Clinical Trial With Evaluation of Molecular Effects With Sorafenib Tosylate for Patients With Stage II or Greater Renal Cell Carcinoma
- Determine the safety and feasibility of systemic sorafenib tosylate therapy when given
prior to definitive nephrectomy in patients with stage II-IV renal cell carcinoma
- Determine all levels of response in primary renal tumors of patients treated with this
- Assess effects of this drug on gene expression, protein expression, and metabolic
profile using tumor tissue samples from these patients.
- Identify biomarkers or biomarker patterns associated with RCC or this drug in these
OUTLINE: This is a pilot, open-label, nonrandomized study.
Patients receive oral sorafenib tosylate twice daily for 4-8 weeks in the absence of disease
progression or unacceptable toxicity. After completion of neoadjuvant therapy, patients
undergo surgical resection of their kidney tumor.
Patients undergo blood and urine sample collection at baseline and after completion of
treatment (i.e., at 4 and 8* weeks) for VEGF analysis. Samples are examined by enzyme-linked
immunosorbent assay for measurement of serum and urinary VEGF levels.
NOTE: *Blood sampling at 8 weeks is only for those patients undergoing 8 weeks of study
Patients also undergo tissue sample collection at the time of nephrectomy. Tissue samples
are examined by microarray analysis and IHC staining for expression of CD31/PECAM, HIF1α,
and HIF2α. Immunohistochemical staining to identify biomarkers of microvessel density is
also performed. Tissue samples are also examined for gene expression and metabolic profile
by small molecule mass spectroscopy, as well as VHL gene mutation by VHL mutation analysis.
Patients are followed at 4-8 weeks after nephrectomy.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Number of subjects experiencing adverse events while taking sorafenib prior to nephrectomy
Adverse events will be assessed (graded) using CTCAE criteria
W. Kimryn Rathmell, MD, PhD
UNC Lineberger Comprehensive Cancer Center
United States: Institutional Review Board
|Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill||Chapel Hill, North Carolina 27599-7570|