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

This is an interventional treatment trial for Recurrent Melanoma Read More

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