Pazopanib Hydrochloride in Treating Patients With Metastatic Melanoma That Cannot be Removed by Surgery
Condition: Recurrent Melanoma; Stage IV Cutaneous Melanoma AJCC v6 and v7
MeSH terms: Melanoma
Intervention: Laboratory Biomarker Analysis; Pazopanib Hydrochloride; Pharmacological Study
Intervention description: Correlative studies; Given orally; Correlative studies
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 13.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying the side effects of pazopanib hydrochloride and to see how
      well it works in treating patients with metastatic melanoma that cannot be removed by
      surgery. Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the
      enzymes needed for cell growth and by blocking blood flow to the tumor.
    

Eligibility criteria:

        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