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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Kidney Cancer, Melanoma (Skin), Metastatic Cancer

Intervention / Treatment
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* Drug: sunitinib malate


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sunitinib<br>Patients will be treated with 50 mg daily for four out of every six weeks. | Drug: sunitinib malate<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Central Nervous System (CNS) Response Rate by RECIST Criteria | Response and progression will be evaluated in this study using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used in RECIST. Measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques (CT, MRI, X-ray) or as >10 mm with spiral CT scan. This study will use a minimum diameter of 10 mm for measurable lesions in the brain, regardless of imaging modality. All tumor measurements must be recorded in millimeters (or decimal fractions of centimeters). All other lesions are considered non-measurable disease. Bone lesions, leptomeningeal disease, ascites, pleural/pericardial effusions, inflammatory breast disease, and cystic lesions are all nonmeasurable. | up to a year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IV melanoma, tumors metastatic to brain, stage IV renal cell cancer, recurrent melanoma, recurrent renal cell cancer