Sunitinib in Treating Patients With Brain Metastases Caused by Kidney Cancer or Melanoma

OBJECTIVES:

Primary

• Determine the efficacy of sunitinib malate, in terms of objective radiographic response of brain lesions, in patients with brain metastases secondary to renal cell carcinoma or melanoma.

Secondary

• Determine overall and progression-free survival.

OUTLINE: Patients receive oral sunitinib malate once daily on days 1-28. Courses repeat every 6 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed periodically.

DISEASE CHARACTERISTICS:

• Histologically confirmed melanoma or renal cell carcinoma

• Metastatic brain disease
• Must have assessable target intracranial lesion(s), defined as measurable disease ≥ 10 mm in longest diameter that is not appropriate for stereotactic radiosurgery or surgical resection

• Lesions previously treated with radiosurgery AND not eligible for resection can only be used as target lesions if there has been true tumor progression on baseline scan (i.e., ≥ 20% increase in longest diameter of lesion) rather than radionecrosis

• True progression must be confirmed by PET scan or other corroborating imaging used to distinguish radionecrosis
• No leptomeningeal metastases or primary dural metastases

PATIENT CHARACTERISTICS:

• ECOG performance status (PS) 0-1 OR Karnofsky PS 60-100%
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Total leukocyte count ≥ 3,000/mm³
• ANC ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Creatinine ≤ 2.0 times upper limit of normal (ULN)
• Bilirubin ≤ 1.5 times ULN
• Hemoglobin ≥ 9.0 g/dL
• Calcium ≤ 12.0 mg/dL
• AST and ALT ≤ 1.5 times ULN
• PT ≤ 1.5 times ULN
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No uncontrolled medical illness including, but not limited to, any of the following:

• Hypertension (i.e., blood pressure > 150/100 mm Hg)
• Thyroid disease
• Severe valvular disease
• Severe pulmonary disease
• HIV/AIDS
• Severe psychiatric illness
• No cardiac dysrhythmia ≥ grade 2
• No prolonged QTc interval on baseline EKG
• No systemic hemorrhage ≥ grade 2 within the past 4 weeks

• No CNS hemorrhage ≥ grade 2

• Grade 1 (asymptomatic) CNS hemorrhage allowed at investigator's discretion
• None of the following within the past 6 months:

• Myocardial infarction
• Unstable angina
• Symptomatic congestive heart failure
• Stroke/transient ischemic attack
• Pulmonary embolism
• Ejection fraction ≥ 50% by baseline echocardiogram OR < 20% decrease in ejection fraction from a prior study

PRIOR CONCURRENT THERAPY:

• No prior multi-targeted tyrosine kinase inhibitor therapy (e.g., sunitinib malate or sorafenib)
• No coronary/peripheral arterial bypass surgery within the past 6 months
• More than 4 weeks since prior surgery and recovered
• More than 4 weeks since prior and no other concurrent experimental therapy or cytotoxic chemotherapy
• More than 4 weeks since prior immunotherapy
• More than 2 weeks since prior stereotactic radiosurgery and recovered
• More than 7 days since prior and no concurrent drugs that interact with CYP3A4 family, including enzyme-inducing antiepileptic drugs, warfarin, or Hypericum perforatum extract (St. John's wort)