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

A Phase II Study of SU11248 (Sunitinib) in Patients With Renal Cell Carcinoma and Melanoma Metastatic to the Brain

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 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)