PXD101 as Second-Line Therapy in Treating Patients With Malignant Mesothelioma of the Chest That Cannot Be Removed By Surgery

Inclusion Criteria

• Histologically or cytologically confirmed malignant pleural mesothelioma (MPM) of any of the following subtypes:
• Epithelial
• Sarcomatoid
• Mixed
• Have received only 1 prior systemic chemotherapy regimen for advanced mesothelioma
• Prior intrapleural cytotoxic agents (including bleomycin) not considered systemic chemotherapy
• Patients who are not candidates for combination chemotherapy are eligible even if they have not received prior chemotherapy
• Unresectable disease
• Measurable disease, defined as >= 1 unidimensionally measurable lesion >= 20 mm by conventional techniques OR >= 10 mm by spiral CT scan
• The sole site of measurable disease must not be located within the radiotherapy port
• No known brain metastases
• ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
• Life expectancy > 3 months
• WBC >= 3,000/mm^3
• Absolute neutrophil count >= 1,500/mm^3
• Platelet count >= 100,000/mm^3
• Bilirubin normal
• AST/ALT = = 50 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective double-barrier contraception for 1 week before, during, and for >= 2 weeks after completion of study treatment
• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to PXD101
• No symptomatic congestive heart failure
• No congestive heart failure related to primary cardiac disease
• No unstable angina pectoris
• No cardiac arrhythmia
• No condition requiring anti-arrhythmic therapy
• No uncontrolled hypertension
• No myocardial infarction within the past 6 months
• No ischemic or severe valvular heart disease
• No ongoing or active infection
• No marked baseline prolongation of QT/QTc interval
• No repeated QTc interval > 500 msec
• No long QT syndrome
• No other significant cardiovascular disease
• No other uncontrolled intercurrent illness
• No psychiatric illness or social situation that would preclude study compliance
• Recovered from prior therapy
• No prior valproic acid or other known histone deacetylase (HDAC) inhibitor
• More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
• More than 3 weeks since prior radiation therapy
• No concurrent medication that may cause torsade de pointes
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent investigational agents
• No other concurrent anticancer agents or therapies