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A Pilot Neoadjuvant Clinical Trial With Evaluation of Molecular Effects With Sorafenib Tosylate for Patients With Stage II or Greater Renal Cell Carcinoma

18 Years
Open (Enrolling)
Kidney Cancer

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Trial Information

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.

Inclusion Criteria


- Diagnosis of renal cell carcinoma (RCC) as confirmed by either of the following:

- Radiographic documentation by MRI or CT scan

- Histological evidence of primary RCC

- Stage II-IV disease, as defined by any of the following:

- T > 7 cm

- Renal vein involvement

- Local invasion

- Evidence of lymph node involvement

- Distant metastatic disease

- Deemed suitable for nephrectomy by a urologist

- No requirement for surgery earlier than 4 weeks from study entry

- No known brain metastasis

- Patients with neurological symptoms must undergo a CT scan or brain MRI to
exclude brain metastasis


- ECOG performance status 0-1

- Hemoglobin ≥ 9.0 g/dL

- ANC ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Bilirubin ≤ 1.5 times upper limit of normal (ULN)

- ALT and AST ≤ 2.5 times ULN (≤ 5 times ULN for patients with liver involvement)

- Creatinine ≤ 2.5 times ULN or glomerular filtration rate ≥ 50 mL/min

- INR ≤ 1.5 AND PTT normal

- Stable INR required at baseline for patients on warfarin

- Not pregnant or nursing

- Negative pregnancy test

- Fertile women must use effective contraception

- Fertile men must use effective contraception during and for ≥ 2 months after the last
dose of sorafenib tosylate

- No other active primary malignancy except skin cancer

- No active coronary artery disease

- No active bleeding diathesis

- Closely monitored therapeutic anticoagulation allowed

- No cardiac disease, including any of the following:

- New York Heart Association class III-IV congestive heart failure

- Unstable angina (i.e., anginal symptoms at rest) or new onset angina (i.e.,
beginning within the past 3 months)

- Myocardial infarction within the past 6 months

- No cardiac ventricular arrhythmias requiring anti-arrhythmic therapy

- No uncontrolled hypertension, defined as systolic blood pressure (BP) > 150 mm Hg or
diastolic BP > 90 mm Hg, despite optimal medical management

- No known HIV infection or chronic hepatitis B or C

- No active, clinically serious infection > grade 2

- No thrombolic or embolic events, such as a cerebrovascular accident or transient
ischemic attacks, within the past 6 months

- No pulmonary hemorrhage or bleeding event ≥ grade 2 within the past 4 weeks (≥ grade
3 for any nonpulmonary hemorrhage or bleeding event)

- No serious nonhealing wound, ulcer, or bone fracture

- No significant traumatic injury within the past 4 weeks

- No known or suspected allergy to sorafenib tosylate or any agent given in the course
of this study

- No condition that impairs the patient's ability to swallow whole pills

- No malabsorption problem


- No major surgery or open biopsy within the past 4 weeks

- Concurrent anticoagulation therapy (e.g., warfarin or heparin) allowed

- No other concurrent investigational or commercial agents or therapies for RCC

- No concurrent Hypericum perforatum (St. John's wort) or rifampin

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of subjects experiencing adverse events while taking sorafenib prior to nephrectomy

Outcome Description:

Adverse events will be assessed (graded) using CTCAE criteria

Outcome Time Frame:

8 weeks

Safety Issue:


Principal Investigator

W. Kimryn Rathmell, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UNC Lineberger Comprehensive Cancer Center


United States: Institutional Review Board

Study ID:

LCCC 0603



Start Date:

November 2006

Completion Date:

November 2013

Related Keywords:

  • Kidney Cancer
  • stage II renal cell cancer
  • stage III renal cell cancer
  • stage IV renal cell cancer
  • Carcinoma, Renal Cell
  • Kidney Neoplasms



Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill Chapel Hill, North Carolina  27599-7570