Sorafenib in Treating Patients With Kidney Cancer That Has Spread to the Brain

A Phase 2 Study of Sorafenib (BAY 43-9006) in Metastatic Renal Cell Cancer to the Brain

This phase II trial is studying how well sorafenib works in treating patients with kidney cancer that has spread to the brain. 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.

Study Overview

• Status: Completed
• Conditions: Kidney Cancer; Metastatic Cancer
• Intervention / Treatment: Drug: sorafenib tosylate

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the partial and minor response rate in patients with renal cell carcinoma (RCC) metastatic to the brain treated with sorafenib.

SECONDARY OBJECTIVES:

I. Determine the toxicity of sorafenib in patients with RCC metastatic to the brain.

II. Determine whether the effect of sorafenib on RCC metastatic to the brain is similar to its effect on non-brain metastatic sites.

OUTLINE: This is a multicenter study.

Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically.

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637-1470
      • University of Chicago Cancer Research Center
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital Cancer Care Institute
    • Evanston, Illinois, United States, 60201-1781
      • Evanston Northwestern Health Care - Evanston Hospital
    • Harvey, Illinois, United States, 60426
      • Ingalls Cancer Care Center at Ingalls Memorial Hospital
    • Maywood, Illinois, United States, 60153
      • Cardinal Bernardin Cancer Center at Loyola University Medical Center
    • Peoria, Illinois, United States, 61615-7828
      • Oncology Hematology Associates of Central Illinois, PC - Peoria
    • Springfield, Illinois, United States, 62701
      • Central Illinois Hematology Oncology Center
  • Indiana
    • Fort Wayne, Indiana, United States, 46885-5099
      • Fort Wayne Medical Oncology and Hematology
    • South Bend, Indiana, United States, 46601
      • CCOP - Northern Indiana CR Consortium
  • Michigan
    • Saint Joseph, Michigan, United States, 49085
      • Oncology Care Associates, PLLC
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • David C. Pratt Cancer Center at St. John's Mercy
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed renal cell carcinoma metastatic to the brain
• Measurable disease in the brain

• Meets 1 of the following criteria:

  • No prior brain-specific therapy AND no CNS symptoms referable to the brain lesion(s) (with or without concurrent steroid therapy)
  • CNS symptoms referable to the brain lesion(s) AND received primary therapy for the brain lesion(s)

PATIENT CHARACTERISTICS:

• Blood pressure < 140/90 mm Hg on 2 separate occasions, taken at least 24 hours apart, within the past 6 weeks (patients on stable anti-hypertensive regimens allowed)
• ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
• Bilirubin < 1.5 times upper limit of normal (ULN)
• ALT/AST < 2.5 times ULN
• Estimated glomerular filtration rate > 30 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Able to swallow pills or comply with an oral treatment regimen
• No history of a bleeding diathesis or requirement for full-dose anticoagulation
• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to sorafenib
• No clinical or radiologic evidence of bowel obstruction or perforation

• No other uncontrolled intercurrent illness including, but not limited to, any of the following:

  • Ongoing or active infection
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric illness or social situation that would limit compliance with study requirements

PRIOR CONCURRENT THERAPY:

• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered
• More than 4 weeks since prior radiotherapy to sites outside of the brain and recovered
• More than 8 weeks since prior standard external-beam radiotherapy to the brain unless there is evidence of in-brain progression
• No prior complete surgical resection or radiosurgery of all known brain metastases unless there is evidence of in-brain progression
• No prior sorafenib, sunitinib malate, bevacizumab, or any other agent targeting the platelet-derived growth factor receptor (PDGFR) or vascular endothelial growth factor receptor (VEGFR) kinase cascade
• No other concurrent investigational agents

• No concurrent enzyme-inducing anti-seizure medications, including phenytoin, phenobarbital, carbamazepine, or primidone

  • Concurrent non-enzyme-inducing anti-seizure medications allowed
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No concurrent hematopoietic growth factors except erythropoietin
• No concurrent ketoconazole, itraconazole, or ritonavir
• No concurrent grapefruit juice
• No concurrent Hypericum perforatum (St. John's wort)
• No concurrent chemotherapy
• No concurrent hormonal therapy except steroids for adrenal failure and/or control of CNS edema or hormones for non-disease related conditions (e.g., insulin for diabetes)
• No concurrent palliative radiotherapy
• No other concurrent anticancer therapy
• Concurrent bisphosphonates allowed

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I; Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Drug: sorafenib tosylate

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Response rate by RECIST radiologic measurements every 8 weeks

Secondary Outcome Measures

Outcome Measure
Safety by Common Toxicity Criteria version 3.0 every 4 weeks

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Walter M. Stadler, MD, FACP, University of Chicago

Study record dates

Study Major Dates

• Study Start: November 1, 2005
• Primary Completion (Actual): June 1, 2007

Study Registration Dates

• First Submitted: March 9, 2006
• First Submitted That Met QC Criteria: March 9, 2006
• First Posted (Estimate): March 13, 2006

Study Record Updates

• Last Update Posted (Estimate): February 11, 2013
• Last Update Submitted That Met QC Criteria: February 8, 2013
• Last Verified: April 1, 2006

More Information

Terms related to this study

• Keywords: stage IV renal cell cancer; recurrent renal cell cancer; tumors metastatic to brain
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Sorafenib
• Other Study ID Numbers: NCI-2012-02689; UCCRC-14227; NCI-7296; CDR0000462558 (Registry Identifier: PDQ (Physician Data Query))