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