Sorafenib in Treating Patients With Metastatic or Unresectable Kidney Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Bayer
Information provided by (Responsible Party):
University of Nebraska
ClinicalTrials.gov Identifier:
NCT00496756
First received: July 3, 2007
Last updated: December 13, 2013
Last verified: December 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.

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 Intervention Phase
Kidney Cancer
Drug: sorafenib tosylate
Other: flow cytometry
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Sorafenib in Patients With Metastatic Renal Cell Carcinoma

Resource links provided by NLM:


Further study details as provided by University of Nebraska:

Primary Outcome Measures:
  • Toxicity of intrapatient dose escalation of sorafenib tosylate [ Time Frame: Study completion ] [ Designated as safety issue: Yes ]
    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:
  • Response Rate [ Time Frame: from the start of the treatment until disease progression/recurrence ] [ Designated as safety issue: No ]
    The proportion of subjects with an objective response of complete or partial based on the RECIST Criteria

  • Time to progression [ Time Frame: from the start of study treatment to disease progression or death ] [ Designated as safety issue: No ]
    Time to progression survival will be defined as the number of days from the day the subject was consented to the day the subject experiences an event of disease progression, or to the date of death if disease progression is not reached.

  • Overall survival [ Time Frame: From start of study treatment until death ] [ Designated as safety issue: No ]
    Time to death for a given subject will be defined as the number of days from the day the subject was consented to the date of the subject's death.


Enrollment: 14
Study Start Date: March 2007
Estimated Study Completion Date: January 2015
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Sorafenib Drug: sorafenib tosylate
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
Other: flow cytometry
15 ml of blood drawn for flow cytometry of T4/T8, NK, CD25+, and Fox p3 testing obtained at baseline and on days 28, 56, 84, and 112
Other: laboratory biomarker analysis
15 ml of plasma and urine for storage and future determination of VEGF concentration will be obtained at baseline.10 ml of plasma and urine for storage and future determination of VEGF concentration will be obtained on days 28, 56, 84 and 112

Detailed Description:

OBJECTIVES:

Primary

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

Secondary

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

Tertiary

  • 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.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

  • 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

PRIOR CONCURRENT THERAPY:

  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00496756

Locations
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
Bayer
Investigators
Principal Investigator: Ralph Hauke, MD University of Nebraska
  More Information

Additional Information:
No publications provided

Responsible Party: University of Nebraska
ClinicalTrials.gov Identifier: NCT00496756     History of Changes
Other Study ID Numbers: 081-06, P30CA036727, UNMC-08106
Study First Received: July 3, 2007
Last Updated: December 13, 2013
Health Authority: United States: Food and Drug Administration

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:
Carcinoma, Renal Cell
Kidney Neoplasms
Adenocarcinoma
Carcinoma
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 April 14, 2014