This phase II trial is studying how well PXD101 works as second-line therapy in treating patients with malignant mesothelioma of the chest that cannot be removed by surgery. PXD101 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.

PRIMARY OBJECTIVES:

I. Determine the objective response rate in patients with unresectable malignant pleural mesothelioma (MPM) treated with PXD101.

SECONDARY OBJECTIVES:

I. Determine the overall survival and time to progression in these patients. II. Assess the toxicities associated with this drug in these patients. III. Perform molecular correlative studies on tumor tissue (optional) and peripheral blood (required) and identify potential predictive markers for response.

OUTLINE:

Patients receive PXD101 IV over 30 minutes on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo blood collection during course 1 of treatment for biomarker correlative studies. Fetal hemoglobin (hemoglobin F) levels are measured via reverse transcriptase-polymerase chain reaction as a potential predictive marker for response.

After completion of study treatment, patients are followed periodically.

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 =< 2.5 times upper limit of normal

• Creatinine normal OR creatinine clearance >= 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