Clinical trial NCT00459862 (phase 2, status: completed)
Conditions: advanced malignant mesothelioma, localized malignant mesothelioma, recurrent malignant mesothelioma
ICD codes: C45.9, C45.0, C45.1, C45.2, C45.7
Drugs: pazopanib hydrochloride
SMILES: CN(C1=CC2=NN(C)C(C)=C2C=C1)C1=CC=NC(NC2=CC=C(C)C(=C2)S(N)(=O)=O)=N1
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