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

Phase II Study, Multicenter, Open-label, Evaluating Efficacy of Treatment With Sutent® (Sunitinib) in Patients With Previously Untreated or Recurrent Brain Metastases Originating From Renal Cancer

RATIONALE: Sunitinib 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 sunitinib works in treating patients with kidney cancer that has spread to the brain.

OBJECTIVES:

Primary

• Determine the objective response rate in the brain after 2 courses of sunitnib malate in patients with previously untreated or recurrent brain metastases secondary to renal cancer following radiotherapy or surgery.

Secondary

• Evaluate duration of response.
• Evaluate objective response of non-CNS targets.
• Evaluate time to disease progression.
• Evaluate overall and progression-free survival.
• Evaluate neurological symptoms associated with the tumor.
• Evaluate feasibility and overall tolerance of this drug.

OUTLINE: This is a multicenter study.

Patients receive oral sunitinib malate once daily for 4 weeks. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 6 months.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed adenocarcinoma of the kidney

  • Metastatic disease

• Measurable disease by RECIST criteria

• Presence of previously untreated or recurrent brain metastases following radiotherapy or surgery

  • No brain metastasis revealed by hemorrhage
  • No single brain metastasis < 2 cm that is accessible by surgery or radiosurgery

PATIENT CHARACTERISTICS:

• WHO performance status 0-2 (unless paresis due to brain metastases)

• ANC > 1,500/mm^3

• Platelet count > 100,000/mm^3

• Hemoglobin > 8 g/dL

• PT or INR < 1.5 times upper limit of normal (ULN)

• AST/ALT < 2.5 times ULN (< 5 times ULN in the case of liver metastases)

• Total bilirubin < 1.5 times ULN

• Serum creatinine < 200 μmol/L

• Not pregnant or nursing

• Fertile patients must use effective contraception during and for up to 30 days following completion of study treatment

• No other cancer except for in situ cervical cancer, curatively treated basal cell carcinoma of the skin, or other curatively treated cancer without evidence of recurrence within the past 5 years

• No uncontrolled hypertension (systolic BP ≥ 160 mm Hg and/or diastolic BP ≥ 90 mm Hg)

• None of the following cardiac conditions within the past 6 months:

  • Significant cardiovascular disease
  • NYHA class III-IV congestive heart failure
  • Myocardial infarction
  • Unstable angina
  • Severe arrhythmia
  • Cerebrovascular accident
  • Severe thromboembolism

• No serious neuropsychiatric disease

• No psychological, familial, social, or geographic situations that preclude clinical follow-up

• No patient deprived of liberty by a court or administrative order

• Able to understand French

PRIOR CONCURRENT THERAPY:

• At least 6 months since prior antineoplastic treatment with sunitinib malate
• At least 4 weeks since other prior treatment
• At least 3 weeks since prior hematopoietic growth factors (i.e., filgrastim [G-CSF] or sargramostim [GM-CSF])
• No concurrent antivitamin K at curative or anticoagulation doses