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

Phase 2
18 Years
Open (Enrolling)
Kidney Cancer

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Trial Information

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


- 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

After completion of study treatment, patients are followed periodically.

Inclusion Criteria


- Diagnosis of renal cell carcinoma

- AJCC stage IV disease

- Radiographic evidence of disease for which cytoreductive nephrectomy is deemed to be
clinically indicated AND for which preoperative embolization is not deemed necessary
by the surgeon

- No history or clinical evidence of brain metastases


- ECOG performance status 0-1

- WBC ≥ 3,000/mm³

- Absolute granulocyte count ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Serum creatinine ≤ 2.0 times upper limit of normal (ULN) OR serum creatinine
clearance ≥ 40 mL/min

- Total bilirubin ≤ 1.5 times ULN (< 3.0 times ULN in the presence of Gilbert's

- AST/ALT ≤ 2.5 times ULN (≤ 5.0 times ULN in the presence of liver metastases)

- INR ≤ 1.5*

- PTT normal*

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No pre-existing thyroid abnormality with thyroid-stimulating hormone that cannot be
maintained in the normal range with medication

- No hypertension that cannot be controlled by medications (i.e., diastolic BP ≥ 100 mm
Hg despite optimal medical therapy)

- No ongoing cardiac dysrhythmias ≥ grade 2 (according to NCI CTCAE v3.0)

- No other concurrent malignancies

- No concurrent serious illness including, but not limited to, any of the following:

- Ongoing or active infection requiring parenteral antibiotics

- Clinically significant cardiovascular disease (e.g., uncontrolled hypertension,
myocardial infarction, or unstable angina)

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

- Serious cardiac arrhythmia requiring medication

- Peripheral vascular disease ≥ grade 2 within the past year

- Psychiatric illness/social situation that would limit compliance with study
requirements NOTE: *Patients who are taking warfarin must have documentation of
an INR ≤ 1.5 and PTT normal prior to the initiation of anticoagulation to rule
out a baseline coagulopathy


- At least 2 weeks since prior radiotherapy and recovered

- Prior radiotherapy to a symptomatic site of metastatic disease is allowed

- No prior systemic therapy

- No concurrent cytochrome P450 enzyme-inducing antiepileptic drugs (e.g., phenytoin,
carbamazepine, or phenobarbital), rifampin, or Hypericum perforatum (St. John's wort)

- No other concurrent investigational agents

Type of Study:


Study Design:

Primary Purpose: Treatment

Outcome Measure:

Progression-free survival

Safety Issue:


Principal Investigator

Keith T. Flaherty, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Abramson Cancer Center of the University of Pennsylvania



Study ID:




Start Date:

June 2008

Completion Date:

Related Keywords:

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



Abramson Cancer Center of the University of Pennsylvania Philadelphia, Pennsylvania  19104-4283