Mesothelioma Related Clinical Trials:
A Phase II Study of Sunitinib (SU11248; NSC 736511; IND 74019) in Patients With Advanced Malignant Pleural Mesothelioma

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed malignant pleural mesothelioma
  • Advanced or metastatic disease incurable by standard therapies
• Measurable disease, defined as at least 1 unidimensionally measurable lesion ≥ 20 mm by conventional teachniques or ≥ 10 mm by spiral CT scan
  • No sole site of disease in a previously irradiated area unless there has been subsequent evidence of progression
  • Low-dose, palliative radiotherapy allowed
• Meets 1 of the following criteria for prior cytotoxic chemotherapy treatment:
  • Previously treated with 1 platinum-based chemotherapy regimen
  • Previously untreated (i.e., no prior cytotoxic chemotherapy)
• No known brain metastases

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• Life expectancy ≥ 12 weeks
• Platelet count ≥ 100,000/mm^3
• Absolute granulocyte count ≥ 1,500/mm^3
• Bilirubin normal
• AST and ALT ≤ 2.5 times upper limit of normal
• Calcium ≤ 3 mmol/L
• Creatinine normal OR creatinine clearance ≥ 60 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Patients must reside within a 1.5 hour drive from participating center
• Able to take oral medication
• No other malignancy within the past 5 years except adequately treated nonmelanoma skin cancer, curatively treated in-situ carcinoma of the cervix, or any other curatively treated solid tumor
• No known history of allergic reactions attributed to compounds of similar chemical or biologic composition to sunitinib malate
• No QTc prolongation (i.e., QTc interval ≥ 500 msec) or other significant ECG abnormalities
• No New York Heart Association (NYHA) class III or IV heart failure
• Patients with the following histories allowed provided they are asymptomatic with respect to cardiac function and LVEF is normal by MUGA at baseline:
  • Anthracycline exposure
  • Central thoracic radiation that included the heart
  • NYHA class II cardiac function
• No uncontrolled hypertension (i.e., systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure ≥ 90 mm Hg)
• No cardiac disease within the past 12 months, including any of the following:
  • Myocardial infarction
  • Cardiac arrhythmia
  • Stable/unstable angina
  • Symptomatic congestive heart failure
• No pulmonary embolism within the past 12 months
• No cerebrovascular accident or transient ischemic attack within the past 12 months
• No bowel obstruction or any condition that would impair the ability to swallow and retain sunitinib malate, including any of the following:
  • Gastrointestinal tract disease resulting in an inability to take oral medication
  • Requirement for IV alimentation
  • Active peptic ulcer disease
• No serious illness or medical condition that would preclude study treatment including, but not limited to, any of the following:
  • History of significant neurologic or psychiatric disorder that would impair the ability to obtain consent or limit compliance with study requirements
  • Active uncontrolled infection
  • Any other medical condition that might be aggravated by treatment
  • Serious or nonhealing wound, ulcer, or bone fracture
  • Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
• No pre-existing hypothyroidism unless euthyroid on medication

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered
• At least 7 days since prior and no concurrent CYP3A4 inhibitors, including any of the following:
  • Azole antifungals (e.g., ketoconazole, itraconazole, miconazole)
  • Verapamil
  • Clarithromycin
  • HIV protease inhibitors (e.g., indinavir, saquinavir, ritonavir, atazanavir, or nelfinavir)
  • Erythromycin
  • Delavirdine
  • Diltiazem
• At least 12 days since prior and no concurrent CYP3A4 inducers, including any of the following:
  • Rifampin
  • Phenytoin
  • Rifabutin
  • Hypericum perforatum (St. John's wort)
  • Carbamazepine
  • Efavirenz
  • Phenobarbital
  • Tipranavir
• At least 4 weeks since prior major surgery and recovered
• At least 4 weeks since prior radiotherapy and recovered
• At least 12 months since prior coronary/peripheral artery bypass graft or stenting
• No prior surgical procedures affecting absorption
• No prior radiotherapy that involved ≥ 30% of functioning bone marrow
• No prior treatment with any other antiangiogenic agents or multitargeted tyrosine kinase inhibitors, including any of the following:
  • Bevacizumab
  • Sorafenib tosylate
  • Pazopanib
  • Thalidomide
  • AZD2171
  • Vandetanib
  • AMG706
  • Vatalanib
  • VEGF Trap
• No prior angiogenesis inhibitors except epidermal growth factor receptor inhibitors or other noncytotoxic therapy
• No other concurrent anticancer therapy or treatment with other investigational anticancer agents
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No concurrent therapeutic doses of coumadin-derivative anticoagulants (e.g., warfarin)
  • Doses ≤ 2 mg/day for prophylaxis of thrombosis or low molecular weight heparin for patients with an INR < 1.5 are allowed
• No concurrent agents with proarrhythmic potential, including any of the following:
  • Terfenadine
  • Quinidine
  • Procainamide
  • Disopyramide
  • Sotalol
  • Probucol
  • Bepridil
  • Haloperidol
  • Risperidone
  • Indapamide
  • Flecainide