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Trial record 1 of 58 for:    "Clear Cell Renal Cell Carcinoma" | "Protein Kinase Inhibitors"
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Sorafenib in Treating Patients With Locally Advanced or Metastatic Kidney Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00727532
Recruitment Status : Terminated (Low Accrual)
First Posted : August 4, 2008
Results First Posted : May 3, 2019
Last Update Posted : May 3, 2019
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Northwestern University

Brief Summary:

RATIONALE: Sorafenib 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 sorafenib before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This clinical trial is studying how well sorafenib works in treating patients with locally advanced or metastatic kidney cancer.

Condition or disease Intervention/treatment Phase
Hereditary Clear Cell Renal Cell Carcinoma Kidney Cancer Drug: Sorafenib Not Applicable

Detailed Description:



  • To demonstrate the feasibility and safety of sorafenib tosylate when given prior to nephrectomy or metastasectomy.
  • To evaluate the ability of diffusion-weighted magnetic resonance imaging (DW-MRI) to detect early and ongoing microstructural changes in primary and metastatic renal cell carcinoma lesions during neoadjuvant therapy with sorafenib tosylate.
  • To correlate early and ongoing microstructural changes in primary and metastatic renal cell carcinoma lesions with pathologic and clinical findings at the time of nephrectomy or metastasectomy.
  • To evaluate the ability of changes in DW-MRI to predict subsequent favorable response to treatment (complete or partial response or stable disease) after 4 weeks of therapy.

OUTLINE: Patients receive oral sorafenib tosylate twice daily on days 1-28. Patients then undergo a nephrectomy or metastasectomy in week 5. Patients with residual metastatic disease may continue sorafenib tosylate twice daily and undergo a diffusion-weighted MRI (DW-MRI) every 8 weeks in the absence of disease progression or unacceptable toxicity.

Patients undergo a DW-MRI of the abdomen and pelvis at baseline and prior to week 5 to evaluate microstructure tumor changes and to allow for prediction of sorafenib tosylate benefit. DW-MRI results are correlated with surgical and pathologic findings obtained at week 5.

Resected tumor tissue are analyzed for vascular density and to distinguish apoptotic cell death from necrotic cell death via immunohistochemistry and to measure apoptotic cell death via TUNEL assay.

After completion of study treatment, patients are followed every 3 months for 2 years.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 9 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Correlation of Pathologic Findings After Neo-adjuvant Sorafenib With Results of Diffusion-Weighted Magnetic Resonance Imaging in Patients With Locally Advanced or Metastatic Clear Cell Renal Cell Carcinoma
Study Start Date : July 2008
Actual Primary Completion Date : October 2011
Actual Study Completion Date : September 2013

Arm Intervention/treatment
Experimental: Sorafenib
Eligible patients undergo pre-treatment DW-MRI of the abdomen and pelvis. Patient then receive Sorafenib 400mg orally twice daily on days 1-28. Following completion of 28 days of sorafenib, patients obtain a second DW-MRI.
Drug: Sorafenib
400mg by mouth twice daily for 28 consecutive days
Other Name: Nexavar

Primary Outcome Measures :
  1. Percentage Change in Difference in Apparent Diffusion Coefficient Between Baseline and Week 5 [ Time Frame: Baseline and week 5 ]
    Mean Difference in Apparent Diffusion Coefficient [Time Frame: Baseline and Week 5] To assess whether changes in the apparent diffusion coefficient (ADC) during neoadjuvant sorafenib treatment are detectable in locally advanced or metastatic kidney cancer. The ADC value will be calculated at baseline (within 28 days of initiating sorafenib) and Week 5, and the mean difference will be calculated. The percent change between this mean difference is reported. Week 5 ADC value minus baseline ADC value/divided by baseline ADC value was calculated for each participant. Apparent diffusion coefficient (ADC), obtained by measuring diffusion values at magnetic resonance imaging (MRI), is a measure of water mobility. Lower values correspond to tumor and higher values are consistent with cysts. With sorafenib therapy, the amount of free water may increase in a lesion due to necrosis, and as a result the ADC may increase in value.

  2. Change in Tumor Size From Baseline to Approximately 29-34 Days After Completion of Neoadjuvant Sorafenib Treatment [ Time Frame: Just prior to study week 5 ]
    Tumors were measured at baseline and approximately 29-34 days after completion of neoadjuvant treatment with sorafenib (just prior to surgery). Tumors were assessed by RECIST response criteria.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically confirmed newly diagnosed clear cell renal cell carcinoma, meeting 1 of the following criteria:

    • Localized disease, as evidenced by intact, bulky, and primary renal lesions (T1 > 3 cm, any T2, T3, or T4) appropriate for nephrectomy
    • Limited metastatic disease, as evidenced by any renal primary (T1 > 3 cm, any T2, T3, or T4) appropriate for cytoreductive nephrectomy
    • Isolated abdominal/pelvic recurrence with limited metastatic burden (minimum size > 2 cm) appropriate for metastasectomy
  • No known brain metastasis

    • Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis


  • Eastern Cooperative Oncology Group performance status 0-1
  • Hemoglobin ≥ 9.0 g/dL
  • Absolute neutrophil count ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • Alanine aminotransferase and Aspartate aminotransferase ≤ 2.5 times ULN (≤ 5 times ULN with liver involvement)
  • Creatinine ≤ 1.5 times ULN
  • Estimated glomerular filtration rate > 30 mL/min (for patients receiving Gd-enhanced MRI)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception prior to, during (men and women), and for at least 3 months after (men) completion of study therapy
  • Adequate cardiac and pulmonary status for operative therapy
  • No active clinically serious infection > CTCAE grade 2
  • No known HIV, hepatitis B, or hepatitis C infections
  • No serious non-healing wound, ulcer, or bone fracture
  • No significant traumatic injury within the past 4 weeks
  • No pulmonary hemorrhage/bleeding event ≥ CTCAE grade 2 within the past 4 weeks
  • No other hemorrhage/bleeding event ≥ CTCAE grade 3 within the past 4 weeks
  • No history of an uncontrolled bleeding disorder including, but not limited to, any of the following:

    • Bleeding diathesis
    • Coagulopathy
  • No cardiac disease or condition including, but not limited to, any of the following:

    • New York Heart Association class II-IV congestive heart failure
    • Unstable angina (anginal symptoms at rest)
    • New onset angina beginning within the last 3 months
    • Myocardial infarction within the past 6 months
    • Cardiac ventricular arrhythmias requiring antiarrhythmic therapy
  • No uncontrolled hypertension (i.e., systolic blood pressure [BP] > 150 mm Hg or diastolic BP > 100 mm Hg) despite optimal medical management
  • No thrombolic or embolic events within the past 6 months (e.g., cerebrovascular accident including transient ischemic attacks)
  • No condition that impairs the ability to swallow whole pills
  • No malabsorption problem
  • No contraindication to MRI, including, but not limited to, any of the following:

    • Ferromagnetic implants
    • Dental work
    • Pacemakers
    • Metallic implants
    • Severe claustrophobia which precludes closed MRI testing
  • No known or suspected allergy to sorafenib tosylate
  • No contraindication or allergy to gadolinium (e.g., end stage renal disease requiring hemodialysis)
  • No intercurrent illness or situation which, in the judgment of the investigator, would affect assessments of clinical status and study endpoints significantly


  • See Disease Characteristics
  • More than 4 weeks since prior major surgery or open biopsy
  • No prior therapy with tyrosine kinase or vascular endothelial growth factor inhibitors (e.g., sunitinib malate, sorafenib, or bevacizumab)
  • No concurrent Hypericum perforatum (St. John's wort) or rifampin
  • No concurrent use of illicit drugs or other substances that may, in the opinion of the investigator, have a reasonable chance of contributing to toxicity or interfering with study results

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00727532

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United States, Illinois
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
Chicago, Illinois, United States, 60611-3013
Sponsors and Collaborators
Northwestern University
National Cancer Institute (NCI)
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Principal Investigator: Timothy M. Kuzel, MD Robert H. Lurie Cancer Center

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Responsible Party: Northwestern University Identifier: NCT00727532     History of Changes
Other Study ID Numbers: NU 07U1
P30CA060553 ( U.S. NIH Grant/Contract )
NU-IRB-STU00003123 ( Other Identifier: Northwestern University IRB )
First Posted: August 4, 2008    Key Record Dates
Results First Posted: May 3, 2019
Last Update Posted: May 3, 2019
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by Northwestern University:
clear cell renal cell carcinoma
hereditary clear cell renal cell carcinoma
recurrent renal cell cancer
stage I renal cell cancer
stage II renal cell cancer
stage III renal cell cancer
stage IV renal cell cancer
Additional relevant MeSH terms:
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Protein Kinase Inhibitors
Carcinoma, Renal Cell
Kidney Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action