Belinostat (PXD101) to Treat Tumors of the Thymus at an Advanced Stage

• INCLUSION CRITERIA:

Histologically confirmed invasive recurrent or metastatic thymoma or thymic carcinoma by the pathology department / Center for Cancer Research (CCR) / National Cancer Institute (NCI).

Patients must have had at least one prior platin-containing chemotherapy regimen. There is no limit to the number of prior chemotherapy regimens received. Progressive disease should have been documented before entry into the study.

Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as greater than 20 mm with conventional techniques or as greater than 10 mm with spiral computed tomography (CT) scan.

Patients must have recovered from toxicity related to prior therapy to at least to grade 1 (defined by the Common Terminology Criteria for Adverse Events (CTCAE) 3.0 until December 31, 2010, and by CTCAE 4.0 beginning January 1, 2011) and must not have had prior chemotherapy within 4 weeks. Patients must be at least 28 days since any prior radiation or major surgery.

• Target lesions cannot be selected within previously irradiated areas, if not newly arising or clearly progressing after irradiation as proven by repeat scanning.
• Concurrent corticosteroids for myasthenia gravis, or other paraneoplastic syndromes, or other chronic conditions are allowed.

Age greater than 18 years.

Life expectancy of greater than 3 months.

Performance status (Eastern Cooperative Oncology Group (ECOG)) less than or equal to 2.

Patients must have adequate organ and marrow function (as defined below). Patients must have returned to base line or grade one from any acute toxicity related to prior therapy.

Laboratory Test/Required Value:

Absolute neutrophil count greater than 1,500/microl.

Platelets greater than 100,000/microl.

International normalized ratio (INR) less than or equal to 1.5 times upper limit of normal (ULN) or

Partial thromboplastin time (PTT) abnormality can be explained by the presences of lupus anticoagulant or in the therapeutic range if on anticoagulation.

Total bilirubin less than or equal to 1.5 times institutional upper limits of normal.

Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase(SGOT) and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase(SGPT) less than or equal to 3 times institutional upper limit of normal.

Creatinine less than or equal to 1.5 times institutional upper limits of normal or Calculated Creatinine greater than 45 mL/min/1.73 m^2 for patients with creatinine.

Clearance levels above institutional normal.

The effects of belinostat on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because histone deacetylase (HDAC) inhibitors are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and continue for at least 2 months after completion. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with belinostat, breastfeeding should be discontinued if the mother is treated with belinostat.

Ability to comply with intravenous administration schedule, and the ability to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA

Patients with symptomatic brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. However, patients who have had treatment for their brain metastases and whose brain metastatic disease st