Investigator left the institute.

RATIONALE: Lenalidomide may stop the growth of tumor cells by blocking blood flow to the tumor. Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving lenalidomide together with sunitinib and low doses of cyclophosphamide once a day may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving lenalidomide together with sunitinib and cyclophosphamide works in treating patients with stage IV eye melanoma.

OBJECTIVES:

Primary

• Determine the response rate in patients with stage IV ocular melanoma treated with lenalidomide, sunitinib malate, and low-dose metronomic cyclophosphamide.

Secondary

• Determine the toxicity of this regimen in these patients.
• Determine the progression-free survival of patients treated with this regimen.
• Obtain blood, urine, and tissue samples from these patients, when easily accessible, to determine the effects of this regimen on pathways thought to have been modulated by this regimen in pre-clinical studies.

OUTLINE: This is nonrandomized, uncontrolled, open-label study.

Patients receive oral lenalidomide, oral sunitinib malate*, and oral low-dose cyclophosphamide once daily on days 1-28. Treatment repeats every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

NOTE: *Some patients will not receive sunitinib malate during course 1.

After completion of study treatment, patients are followed every 3 months for 2 years, every 4 months for 3 years and then annually thereafter.

DISEASE CHARACTERISTICS:

• Histologically confirmed ocular melanoma

  • Stage IV disease

• Measurable disease

• No active brain metastases

  • Patients with brain metastases must have had a complete excision or radiotherapy and remain asymptomatic with stable disease by magnetic resonance imaging (MRI) or computed tomography (CT) scan for ≥ 6 months

PATIENT CHARACTERISTICS:

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2

• Life expectancy > 3 months

• Granulocyte count > 1,500/mm^3

• Platelet count > 100,000/mm^3

• Creatinine ≤ 1.5 mg/dL OR creatinine clearance > 60 mL/min

• Bilirubin ≤ 2.0 mg/dL

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 10 times upper limit of normal (ULN)

• Prothrombin time (PT)/partial thromboplastin time (PTT)/International Normalized Ratio (INR) normal

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use one highly effective method of contraception (with an additional method) or barrier methods of contraception for ≥ 4 weeks before, during, and for ≥ 4 weeks after completion of study therapy

• Ejection fraction normal by echocardiogram

• No acute, critical illness, including serious untreated infection

• No history of any of the following:

  • Unstable or newly diagnosed angina pectoris
  • Myocardial infarction within the past 6 months
  • New York Heart Association class II-IV heart disease
  • Congestive heart failure
  • Chronic obstructive lung disease requiring oxygen therapy
  • Chronic uncontrollable hypertension
  • Uncontrolled seizure activity

• No known human immunodeficiency virus (HIV) positivity

• No known hypersensitivity reaction to thalidomide, lenalidomide, sunitinib malate, or cyclophosphamide

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered from all prior therapy
• At least 4 weeks since prior surgery, chemotherapy (6 weeks for mitomycin C, nitrosoureas, or carboplatin), hormonal therapy, radiotherapy, or biological therapy
• No concurrent grapefruit or grapefruit juice
• No other concurrent antitumor therapy

16 months