Intervention: Pazopanib Hydrochloride
Trial phase: Phase 2
SMILES: Cc1ccc(Nc2nccc(N(C)c3ccc4c(C)n(C)nc4c3)n2)cc1S(N)(=O)=O.Cl
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 34
Group description: Patients receive oral pazopanib hydrochloride once daily on days 1-21. Treatment repeats every 21 days for 2 years in the absence of disease progression or unacceptable toxicity.
Eligibility criteria:
Inclusion Criteria:

Histologically or cytologically confirmed malignant pleural mesothelioma:

Measurable disease
No progressive disease inside or outside of any prior radiation field

No symptomatic, untreated, or uncontrolled CNS metastases

Patients with CNS metastases treated with whole brain radiation (WBRT) may be enrolled after completion of WBRT

Patients may begin study therapy as early as the next day after completion of WBRT
ECOG performance status 0-2
Life expectancy >= 12 weeks
ANC >=1,500/mm^3
Platelet count >= 100,000/mm^3
WBC >= 3,000/mm^3
Bilirubin =< 1.5 times upper limit of normal (ULN)
AST and ALT =< 2.5 times ULN
Alkaline phosphatase =< 2.5 times ULN
Creatinine =< 1.5 times ULN or creatinine clearance >= 50 mL/min
Proteinuria =< 1+ on 2 consecutive dipsticks taken >= 1 week apart

No condition that impairs ability to swallow and retain study drug tablets including, but not limited to, any of the following:

Gastrointestinal tract disease resulting in an inability to take oral medication
Requirement for IV alimentation
Prior surgical procedures affecting absorption
Active peptic ulcer disease
No other primary malignancy except for carcinoma in situ of the cervix or nonmelanomatous skin cancer, unless that prior malignancy was diagnosed and definitively treated ≥ 5 years ago with no subsequent evidence of recurrence
Patients with a history of low-grade (Gleason score =< 6) localized prostate cancer are eligible even if diagnosed within the past 5 years
No history of allergic reactions attributed to compounds of similar chemical or biological composition to pazopanib hydrochloride or other agents used in the study

None of the following concurrent severe and/or uncontrolled medical conditions:

Serious or nonhealing wound, ulcer, or bone fracture
Abdominal fistula, diverticulosis, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
Poorly controlled diabetes
Interstitial pneumonia
Extensive and symptomatic interstitial fibrosis of the lung

No cardiovascular illness or complication, including any of the following:

Any history of cerebrovascular accident within the past 6 months
History of myocardial infarction (prior electrocardiographic evidence of myocardial injury)
History of cardiac arrhythmia (prior electrocardiographic evidence of abnormal heart rhythm)
Admission for unstable angina
Cardiac angioplasty or stenting within the past 12 months

NYHA class III-IV heart failure

Asymptomatic NYHA class II heart failure allowed
QTc prolongation (defined as a QTc interval ≥ 500 msecs) or other significant electrocardiogram abnormalities
Venous thrombosis within the past 12 weeks
No ancillary therapy considered investigational within the past 4 weeks
No symptomatic, untreated, or uncontrolled seizure disorder
No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit study compliance
No significant traumatic injury within the past 4 weeks
No more than 1 prior systemic therapy for malignant pleural mesothelioma

No major surgery (i.e., laparotomy) or open biopsy within the past 4 weeks

Insertion of a vascular access device is not considered major or minor surgery

No minor surgery within the past 2 weeks

Insertion of a vascular access device is not considered major or minor surgery

Prior palliative radiotherapy allowed

No prior palliative radiotherapy to the chest except for a maximum of 3 fractions of radiotherapy for superior vena cava syndrome

No concurrent therapeutic warfarin

Low molecular-weight heparin or prophylactic low-dose warfarin allowed
No other concurrent chemotherapy, immunotherapy, hormonal therapy, or radiotherapy
No concurrent medications that act through the CYP450 system
No concurrent combination antiretroviral therapy for HIV-positive patients
PT/INR/PTT =< 1.2 times ULN
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective nonhormonal contraception
No uncontrolled infection
No uncontrolled blood pressure (BP) (defined as systolic BP > 140 mm Hg and/or diastolic BP > 90 mm Hg in spite of adequate anti-hypertensive therapy)
No other severe underlying disease that, in the judgment of the investigator, would limit study compliance