Inclusion Criteria:

- Histologically confirmed unresectable malignant melanoma

- Radiographic or clinical evidence of metastatic disease

- Measurable disease with ≥ 1 lesion whose longest diameter can be measured as ≥ 2.0 cm
by CT or MRI scans or ≥ 1.0 cm by spiral CT scan

- Disease that is measurable by physical examination only is not allowed

- No known intraluminal metastatic lesion(s) with suspected bleeding

- No brain metastases by MRI or CT scan

- ECOG performance status 0-2

- Life expectancy > 12 weeks

- WBC ≥ 3,000/μL

- Hemoglobin ≥ 9 g/dL

- Absolute neutrophil count ≥ 1,500/μL

- Platelets ≥ 100,000/μL

- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

- AST and ALT ≤ 2.5 times ULN

- Creatinine ≤ 1.5 times ULN

- Serum troponin normal

- Urine protein ≤ 1+ (≤ 30 mg/dL) on 2 consecutive dipstick or other urine assessments
taken ≥ 1 week apart

- QTc interval < 480 msec

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No significant ECG abnormalities (e.g., frequent ventricular ectopy, evidence of
ongoing myocardial ischemia)

- No serious nonhealing wound, ulcer, or bone fracture

- No history of abdominal fistula, gastrointestinal perforation, active diverticulitis,
intra-abdominal abscess, or gastrointestinal tract bleeding within the past 28 days

- No history of myocardial infarction, cardiac arrhythmia within the past 6 months

- No NYHA class III-IV heart failure

- Patients with a history of class II heart failure and who are asymptomatic on
treatment may be eligible

- No history of bleeding disorder, including hemophilia, disseminated intravascular
coagulation, or any other abnormality of coagulation potentially predisposing
patients to bleeding

- No uncontrolled infection

- No evidence of active bleeding or bleeding diathesis

- No hemoptysis within 6 weeks of first dose of study drug

- No active peptic ulcer disease

- No inflammatory bowel disease

- No ulcerative colitis or other gastrointestinal conditions with increased risk of
perforation

- No history of cerebrovascular accident, including transient ischemic attack,
pulmonary embolism, or untreated deep venous thrombosis within the past 6 months

- Patients with recent deep vein thrombosis who have been treated with therapeutic
anticoagulating agents within the past 6 weeks are eligible

- No known endobronchial lesions or involvement of large pulmonary vessels by tumor

- No current active hepatic or biliary disease, except Gilbert syndrome, asymptomatic
gallstones, liver metastases, or stable chronic liver disease

- No uncontrolled hypertension (i.e., systolic blood pressure [BP] > 140 mm Hg and
diastolic BP > 90 mm Hg)

- No condition that impairs ability to swallow and retain pazopanib hydrochloride
(e.g., gastrointestinal tract disease resulting in an inability to take oral
medication or a requirement for IV alimentation, prior surgical procedures affecting
absorption, or active peptic ulcer disease)

- No history of allergic reactions attributed to compounds of similar chemical or
biological composition to pazopanib hydrochloride or other agents used in the study

- No uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection or psychiatric illness/social situations that would or might reasonably be
expected to limit compliance with study requirements

- No admission for unstable angina, cardiac angioplasty, or stenting within the past 6
months

- More than 6 weeks since prior major surgery

- More than 4 weeks since prior and no concurrent radiotherapy

- At least 14 days or 5 half-lives and no concurrent CYP interactive medications

- No prior radiotherapy to ≥ 25% of bone marrow

- No prior therapy with a VEGFR tyrosine-kinase inhibitor

- No concurrent antiretroviral therapy for HIV-positive patients

- No concurrent medications or substances known to affect or with the potential to
affect the activity or pharmacokinetics of pazopanib hydrochloride

- No concurrent chemotherapy

- No other concurrent investigational agents

- No other concurrent anticancer agents or therapies

- No concurrent medications that are associated with a risk of QTc prolongation and/or
Torsades de Pointes