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Sorafenib in Treating Patients With Metastatic or Unresectable 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: NCT00496756
Recruitment Status : Terminated (Low accrual rate.)
First Posted : July 4, 2007
Results First Posted : February 15, 2019
Last Update Posted : March 12, 2019
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Nebraska

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.

PURPOSE: This phase II trial is studying the side effects and how well sorafenib works in treating patients with metastatic or unresectable kidney cancer.

Condition or disease Intervention/treatment Phase
Kidney Cancer Drug: Sorafenib Phase 2

Detailed Description:



  • Evaluate the safety and toxicity of dose escalating sorafenib tosylate in patients with metastatic or unresectable renal cell carcinoma.


  • Determine tumor response in these patients.
  • Determine time to progression in these patients.
  • Determine overall survival of these patients.


  • Collect data on angiogenesis inhibition induced by sorafenib tosylate.
  • Collect data on immunomodulatory effects of sorafenib tosylate.

OUTLINE: This is an open-label study.

Patients receive oral sorafenib tosylate twice daily on days 1-28. Treatment repeats every 4 weeks for at least 2 courses in the absence of disease progression or unacceptable toxicity.

Patients receive escalating doses of sorafenib tosylate (in the absence of grade 3 or 4 dose-limiting toxicity) until a pre-determined dose is reached.

Blood and urine samples are collected at baseline and periodically during study for VEGF level determination. Blood samples are analyzed for T4/T8, NK, CD25+, and Fox p3 by flow cytometry. Tumor tissue blocks or unstained slides are obtained for chemistry staining of VEGF.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 14 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Sorafenib in Patients With Metastatic Renal Cell Carcinoma
Study Start Date : March 2007
Actual Primary Completion Date : October 2009
Actual Study Completion Date : April 2014

Arm Intervention/treatment

The initial dose of Sorafenib will be administered orally with a dose of 400 mg twice a day, daily. Intrapatient dose escalation will occur as defined in the table below, providing no dose limiting toxicity (Grade 3 or 4) is observed. If grade 3 or 4 toxicity is observed, delay and dose modification will occur as defined in protocol. Once dose level 3 is reached, the patient will remain at that dose as defined in following section.

Dose Level 1 Day 1-28 400 mg b.i.d. Dose Level 2 Day 29-56 600 mg b.i.d. Dose Level 3 Day 57- 800 mg b.i.d.

A treatment cycle will be 4 weeks.

Two 4-week cycles will be administered. At the completion of two cycles (week 8), restaging will occur. Patients will continue on therapy per study protocol.

Drug: Sorafenib
initial dose of Sorafenib will be administered orally with a dose of 400 mg twice a day, daily.Intrapatient dose escalation will occur providing no dose limiting toxicity (Grade 3 or 4) is observed. Dose level 2 600mg. Dose level 2 800mg

Primary Outcome Measures :
  1. Toxicity of Intrapatient Dose Escalation of Sorafenib Tosylate [ Time Frame: Study completion ]
    To evaluate the toxicity of dose escalating sorafenib, an estimation of the percentage of patients who are unable to tolerate those escalated doses will be made. Patients will be dose escalated every 4 weeks until a maximum dose of 800 mg BID is reached.

Secondary Outcome Measures :
  1. Response Rate [ Time Frame: from the start of the treatment until disease progression/recurrence ]
    The proportion of subjects with an objective response of complete or partial based on the RECIST 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 or cytologically confirmed renal cell carcinoma (RCC)

    • Must have a component of conventional clear cell RCC

      • Predominant clear cell component ≥ 75%
    • Patients with true papillary, sarcomatoid features without any clear cell component, chromophobe, oncocytoma, collecting duct tumors, or transitional cell carcinoma are not eligible
  • Metastatic or unresectable disease
  • Measurable or nonmeasurable disease

    • Measurable disease is defined as any lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan or MRI
    • Nonmeasurable disease includes any of the following:

      • Small lesions with longest diameter < 20 mm by conventional techniques or < 10 mm by spiral CT scan
      • Bone lesions
      • Leptomeningeal disease
      • Ascites
      • Pleural/pericardial effusion
      • Lymphangitis cutis/pulmonitis
      • Abdominal masses that are not confirmed and followed by imaging techniques
      • Cystic lesions
      • Irradiated lesions, unless progression is documented after radiotherapy
  • Paraffin RCC tissue blocks or unstained slides must be obtained for future chemistry staining of VEGF
  • No evidence of CNS metastases

    • No imaging (MRI or CT scan of the brain) abnormality indicative of CNS metastases within the past 42 days


  • Karnofsky performance status 70-100%
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception (hormonal and/or barrier method) during and for 3 months after completion of study treatment
  • Granulocyte count ≥ 1,500/µL
  • Platelet count ≥ 100,000/µL
  • AST/ALT ≤ 2.5 times upper limit of normal (ULN)
  • Alkaline phosphatase ≤ 2.5 times ULN
  • Serum bilirubin ≤ 1.5 times ULN
  • Protein ≤ 1+ by urinalysis
  • Creatinine ≤ 1.5 times ULN
  • No ongoing hemoptysis
  • No cerebrovascular accident within the past 12 months
  • No peripheral vascular disease with claudication while walking less than 1 block
  • No history of clinically significant bleeding
  • No deep venous thrombosis or pulmonary embolus within the past year
  • No significant cardiovascular disease, defined as NYHA class II-IV congestive heart failure, angina pectoris requiring nitrate therapy, or myocardial infarction within the past 6 months
  • No uncontrolled hypertension, defined as systolic BP > 160 mm Hg and/or diastolic BP > 90 mm Hg while on medication
  • No preexisting thyroid abnormality whose thyroid function cannot be maintained in the normal range by medication
  • No uncontrolled psychiatric disorder
  • No delayed healing of wounds, ulcers, and/or bone fractures
  • No currently active second malignancy except nonmelanoma skin cancer

    • Patients are not considered to have a 'currently active' malignancy if they have completed anticancer therapy and are considered by their physician to be at less than 30% risk of relapse


  • At least 4 weeks since prior major surgery and/or radiotherapy and recovered
  • No more than one prior systemic therapy for RCC
  • No prior vascular endothelial growth factor receptor agents
  • Prior palliative radiotherapy for metastatic lesion(s) allowed provided there is at least one measurable and/or evaluable lesion(s) that has not been irradiated
  • More than 4 weeks since prior and no other concurrent anticancer therapy
  • Concurrent continuation of bisphosphonates allowed for bone metastases prophylaxis
  • No concurrent systemic corticosteroid therapy (except replacement therapy for adrenal insufficiency)

    • Topical and/or inhaled steroids allowed
  • No concurrent full-dose oral or parenteral anticoagulation

    • Low-dose warfarin (1 mg) for maintenance of catheter patency or daily prophylactic aspirin allowed
  • No concurrent Hypericum perforatum (St. John's wort)
  • No concurrent ketoconazole, itraconazole, ritonavir, rifampin, or products containing grapefruit juice
  • No concurrent hormonal therapy or chemotherapy

    • Concurrent hormones administered for non-disease related conditions (e.g., insulin for diabetes) allowed

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): NCT00496756

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United States, Nebraska
UNMC Eppley Cancer Center at the University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198-6805
Sponsors and Collaborators
University of Nebraska
National Cancer Institute (NCI)
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Principal Investigator: Ralph Hauke, MD University of Nebraska

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Responsible Party: University of Nebraska Identifier: NCT00496756     History of Changes
Other Study ID Numbers: 081-06
P30CA036727 ( U.S. NIH Grant/Contract )
First Posted: July 4, 2007    Key Record Dates
Results First Posted: February 15, 2019
Last Update Posted: March 12, 2019
Last Verified: February 2019
Keywords provided by University of Nebraska:
clear cell renal cell carcinoma
stage III renal cell cancer
stage IV renal cell cancer
recurrent renal cell cancer
Additional relevant MeSH terms:
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Protein Kinase Inhibitors
Kidney Neoplasms
Carcinoma, Renal Cell
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action