• Maximum tolerated dose and dose-limiting toxicity (DLT) of pazopanib hydrochloride [ Designated as safety issue: Yes ]
  
• Pharmacokinetic (PK) and pharmacodynamic (PD) profiles [ Designated as safety issue: No ]
  
• Non-DLTs [ Designated as safety issue: Yes ]
  
• Correlation of the Child-Pugh classification of hepatic dysfunction with the observed toxicities, plasma PK, and PD of pazopanib hydrochloride [ Designated as safety issue: Yes ]
  
• Antitumor activity [ Designated as safety issue: No ]
  

OBJECTIVES:

• Establish the maximum tolerated dose and dose-limiting toxicity (DLT) of pazopanib hydrochloride in patients with metastatic or unresectable solid tumors or lymphoma and varying degrees of hepatic dysfunction (mild, moderate, or severe) in order to provide appropriate dosing recommendations for pazopanib hydrochloride in these patients.
• Characterize the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of pazopanib hydrochloride and metabolites (GSK1071306, GSK1268992, GSK1268997, and GW700201) in these patients.
• Document the non-DLTs associated with the administration of pazopanib hydrochloride in these patients.
• Correlate the Child-Pugh classification of hepatic dysfunction with the observed toxicities, plasma PK, and PD of pazopanib hydrochloride.
• Document any antitumor activity associated with the administration of pazopanib hydrochloride in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to hepatic function (normal vs mild dysfunction vs moderate dysfunction vs severe dysfunction).

Patients receive oral pazopanib hydrochloride once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Blood samples are collected at baseline and periodically during study for pharmacokinetic and pharmacodynamic studies.

After completion of study therapy, patients are followed for 1 month.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed (at either original diagnosis or a subsequent recurrence) solid tumor or lymphoma

  • Metastatic or unresectable disease
  • Pathologic confirmation of diagnosis is not required in patients with a liver mass, elevated α-fetoprotein level (≥ 500 ng/mL), and positive serology for hepatitis consistent with a diagnosis of hepatocellular carcinoma
• Standard curative or palliative measures do not exist or are no longer effective

• Meets 1 of the following criteria for hepatic function:

  • Normal hepatic function

    • Total bilirubin (> 35% direct) normal AND ALT normal

  • Mild hepatic dysfunction

    • Total bilirubin (> 35% direct) ≤ 1.5 times upper limit of normal (ULN) AND any ALT

  • Moderate hepatic dysfunction

    • Total bilirubin (> 35% direct) ≤ 3 times ULN AND any ALT

  • Severe hepatic dysfunction

    • Total bilirubin (> 35% direct) > 3 times ULN AND any ALT

• No unstable or untreated (non-irradiated) brain metastases

  • Patients with known brain metastases should have undergone brain irradiation (whole brain or gamma knife) > 4 weeks prior to study enrollment

  • Patients who require corticosteroids or anticonvulsants for brain metastases or gliomas must be on a stable dose of corticosteroids and seizure free for ≥ 1 month prior to study enrollment

    • Patients should have had their steroids tapered to low dose (i.e. < 1.5 mg of dexamethasone/day)

PATIENT CHARACTERISTICS:

• Karnofsky performance status 60-100%
• Life expectancy > 3 months
• ANC ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm ^3
• Creatinine normal OR creatinine clearance ≥ 60 mL/min
• Urine protein ≤ 1+ by dipstick urinalysis OR urine protein < 3 g by 24-hour urine collection
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective non-hormonal double barrier contraception prior to, during, and for 3 months after completion of study treatment
• Systolic blood pressure (BP) < 140 mm Hg and diastolic BP < 90 mm Hg (medication allowed)
• History of venous thromboembolism requiring anticoagulation is allowed provided the patient is asymptomatic and stabilized on low molecular weight heparin therapy
• Biliary obstruction for which a shunt has been placed is allowed provided the shunt has been in place for ≥ 10 days prior to the first dose of pazopanib hydrochloride and liver function has stabilized
• No active hemolysis
• No evidence of biliary sepsis

• No concurrent uncontrolled illness including, but not limited to, any of the following:

  • Ongoing or active infection
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric illness or social situation that would preclude study requirements

• No serious or non-healing wound, ulcer, or bone fracture OR class III or IV heart failure as defined by the NYHA functional classification system

  • A history of class II heart failure that is asymptomatic on treatment is allowed

• None of the following illnesses within the past 28 days:

  • Abdominal fistula
  • Gastrointestinal perforation
  • Intra-abdominal abscess

• None of the following illnesses within the past 6 months:

  • Cerebrovascular accident
  • Myocardial infraction
  • Unstable angina
  • Cardiac angioplasty or stenting
• No history of allergic reactions attributed to microcrystalline cellulose, povidone, sodium starch glycolate, magnesium stearate, titanium dioxide (E171), hypromellose (E464), polyethylene glycol 400 (also known as macrogol 400), or polysorbate 80 (E433)
• No inability to swallow whole pills

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered from all prior therapy
• More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
• More than 3 weeks since prior targeted therapy or biological therapy
• More than 4 weeks since prior radiotherapy
• More than 4 weeks since prior major surgery
• More than 1 week and no concurrent CYP450 substrates that may potentially cause serious and/or life-threatening adverse events
• More than 1 week and no concurrent potent CYP3A4 inducers or inhibitors
• No prior pazopanib hydrochloride
• No concurrent combination antiretroviral therapy for HIV-positive patients

• No concurrent full-dose warfarin anticoagulation therapy

  • Prophylactic low-dose warfarin allowed provided PT/PTT and INR ≤ 1.2 times ULN
  • Low molecular weight heparin allowed
• No concurrent hormonal contraceptives
• No other concurrent investigational agents