Pazopanib in Treating Patients With Malignant Pleural Mesothelioma
Condition: Advanced Malignant Mesothelioma; Localized Malignant Mesothelioma; Recurrent Malignant Mesothelioma
MeSH terms: Mesothelioma; Mesothelioma, Malignant; Lung Neoplasms
Intervention: laboratory biomarker analysis; pazopanib hydrochloride
Intervention description: Correlative study; Given orally
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 34.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying the side effects and how well pazopanib works in treating
      patients with malignant pleural mesothelioma. Pazopanib 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 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