• Overall survival by Kaplan-Meier [ Designated as safety issue: No ]
• Time to progression by Kaplan-Meier [ Designated as safety issue: No ]
• Toxicity profile [ Designated as safety issue: Yes ]
• Effect of PXD101 on apoptosis and histone acetylation as measured by TUNEL assay, immunohistochemistry, and western blot [ Designated as safety issue: No ]

• Overall survival by Kaplan-Meier
• Time to progression by Kaplan-Meier
• Toxicity profile
• Effect of PXD101 on apoptosis and histone acetylation as measured by TUNEL assay, immunohistochemistry, and western blot

RATIONALE: 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.

PURPOSE: 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.

OBJECTIVES:

Primary

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

Secondary

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

OUTLINE: This is a multicenter study.

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.

PROJECTED ACCRUAL: A total of 37 patients will be accrued for this study.

• Drug: belinostat
• Genetic: reverse transcriptase-polymerase chain reaction
• Other: laboratory biomarker analysis

DISEASE CHARACTERISTICS:

• 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

PATIENT CHARACTERISTICS:

• ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
• Life expectancy > 3 months
• WBC ≥ 3,000/mm³
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• 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

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• 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