Sorafenib in Treating Patients With Locally Advanced or Metastatic Kidney Cancer

This study has been terminated.
(Low Accrual)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Northwestern University
ClinicalTrials.gov Identifier:
NCT00727532
First received: August 1, 2008
Last updated: July 17, 2013
Last verified: July 2013
  Purpose

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 Intervention
Hereditary Clear Cell Renal Cell Carcinoma
Kidney Cancer
Drug: sorafenib tosylate
Procedure: diffusion-weighted magnetic resonance imaging

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Northwestern University:

Primary Outcome Measures:
  • MRI apparent diffusion coefficients (ADC) at baseline and week 5 [ Time Frame: Baseline and week 5 ] [ Designated as safety issue: No ]
    Patients will undergo a DW-MRI of the pelvis at baseline and prior to week 5 to evaluate microstructure tumor changes and to allow for prediction of sorafenib tosylate benefit

  • Tumor response during the neoadjuvant period [ Time Frame: Just prior to study week 5 ] [ Designated as safety issue: No ]
  • Tumor necrotic fraction and pathology [ Time Frame: At time of surgery ] [ Designated as safety issue: No ]
  • Time to progression [ Time Frame: At time of disease progression ] [ Designated as safety issue: No ]

Enrollment: 9
Study Start Date: July 2008
Estimated Study Completion Date: June 2015
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sorafinib
Sorafinib 400mg orally twice daily on days 1-28
Drug: sorafenib tosylate
400mg by mouth twice daily for 28 consecutive days
Procedure: diffusion-weighted magnetic resonance imaging
At baseline and just prior to surgery after sorafenib treatment

Detailed Description:

OBJECTIVES:

Primary

  • 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-1
  • Hemoglobin ≥ 9.0 g/dL
  • ANC ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • ALT and AST ≤ 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 withing 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

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • More than 4 weeks since prior major surgery or open biopsy
  • No prior therapy with tyrosine kinase or VEGF 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00727532

Locations
United States, Illinois
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
Chicago, Illinois, United States, 60611-3013
Sponsors and Collaborators
Northwestern University
Investigators
Principal Investigator: Timothy M. Kuzel, MD Robert H. Lurie Cancer Center
Principal Investigator: Gary R. Mac Vicar, MD Robert H. Lurie Cancer Center
  More Information

No publications provided

Responsible Party: Northwestern University
ClinicalTrials.gov Identifier: NCT00727532     History of Changes
Other Study ID Numbers: NU 07U1, P30CA060553, NU-07U1, BAYER-NU-07U1, NU-IRB-STU00003123
Study First Received: August 1, 2008
Last Updated: July 17, 2013
Health Authority: United States: Food and Drug Administration
United States: Northwestern University IRB

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:
Carcinoma, Renal Cell
Kidney Neoplasms
Carcinoma
Adenocarcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Sorafenib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 19, 2014