Pazopanib Hydrochloride in Treating Patients With Metastatic Melanoma That Cannot be Removed by Surgery

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