Sorafenib in Treating Patients With Metastatic Kidney Cancer That Has Not Responded to Sunitinib or Bevacizumab

A Phase II Study of Sorafenib in Patients With Metastatic Renal Cell Carcinoma (RCC) Refractory to SU11248 or Bevacizumab Therapy

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 how well sorafenib works in treating patients with metastatic kidney cancer that has not responded to sunitinib or bevacizumab.

OBJECTIVES:

Primary

• To determine the tumor burden reduction rate in patients with sunitinib malate- or bevacizumab-refractory, metastatic clear cell renal cell carcinoma treated with sorafenib tosylate.

Secondary

• To determine the safety of sorafenib tosylate in these patients.
• To record the duration of tumor reduction, time to disease progression, and overall survival of patients treated with sorafenib tosylate.

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

DISEASE CHARACTERISTICS:

• Histologically confirmed renal cell carcinoma with a component of clear cell histology

  • Metastatic disease

• Disease progression, as defined by RECIST criteria, after prior treatment with sunitinib malate or bevacizumab

  • Patients must have received ≥ 1 course (4 weeks) of sunitinib malate or ≥ 2 doses of bevacizumab AND have RECIST-defined objective progression during or within 4 months after completing treatment with sunitinib malate or bevacizumab

• Measurable disease by RECIST criteria

• CNS metastases allowed provided patient has undergone prior surgery and/or radiotherapy AND has no evidence of further CNS disease progression by CT scan or MRI ≥ 2 weeks after treatment of CNS metastases

PATIENT CHARACTERISTICS:

• ECOG performance status (PS) 0-1 or Karnofsky PS 70-100%

• WBC ≥ 3,000/μL

• Absolute neutrophil count ≥ 1,500/μL

• Platelet count ≥ 75,000/μL

• Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

• AST/ALT ≤ 2.5 times ULN

• Creatinine ≤ 2.0 times ULN

• Negative pregnancy test

• No significant cardiovascular disease, including any of the following:

  • Congestive heart failure (New York Heart Association class III-IV heart disease)
  • Active angina pectoris requiring nitrate therapy
  • Uncontrolled dysrhythmias
  • Cardiovascular event within the past 6 months (e.g., transient ischemic attack/cerebrovascular accident, myocardial infarction, or vascular surgery)

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• At least 2 weeks since prior systemic therapy, radiotherapy, or major surgery and recovered
• No prior sorafenib tosylate
• No other concurrent investigational agents
• No other concurrent anticancer therapy
• No concurrent prophylactic growth factors