A Phase 1/2 Study of PXD101 (Belinostat) in Combination With Cisplatin, Doxorubicin and Cyclophosphamide in the First Line Treatment of Advanced or Recurrent Thymic, Malignancies

Inclusion Criteria

• •1. Both the phase I and phase II portions of the protocol will be only open to patients with histologically confirmed advanced stage (Masaoka stage III or IV) thymic malignancies.
• •2. Patients must be chemotherapy na(SqrRoot) ve for the treatment of advanced thymic malignancies.
• •3. Age \> 18 years.
• •4. Eastern Cooperative Oncology Group (ECOG) performance status \< 2 (Karnofsky \> 60%).
• •5. Life expectancy of greater than 3 months.
• •6. Patients must have normal organ and marrow function as defined below:
• •* leukocytes \> 3,000/mcL
• •* absolute neutrophil count \> 1,500/mcL
• •* platelets \> 100,000/mcL
• •* total bilirubin within normal institutional limits
• •* Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT)/alanine aminotransferase (ALT) serum glutamic pyruvic transaminase(SGPT) less than or equal to 5 times the institutional upper limit of normal with evidence of metastatic disease to the liver or less than or equal to 3 times the institutional upper limit of normal without evidence of metastatic disease to the liver
• •* creatinine less than or equal to 1.5 times institutional upper limits of normal
• •OR
• •\- creatinine clearance \> 45 mL/min/1.73 m(2) for patients with creatinine levels above institutional normal.
• •7. 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 \> 20 mm with conventional techniques or as \> 10 mm with spiral computed tomography (CT) scan.
• •8. Patients must have recovered from toxicity related to prior therapy (surgery or radiation) to grade less than or equal to 1 and 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.
• •9. Concurrent corticosteroids for myasthenia gravis, or other paraneoplastic syndromes, or other chronic conditions are allowed.
• •Eligibility of patients receiving any medications or substances known to affect or with the potential to affect the activity or pharmacokinetics of belinostat or cisplatin, doxorubicin or cyclophosphamide will be determined following review of their case by the Principal Investigator. Efforts should be made to switch patients with brain metastases who are taking enzyme-inducing anticonvulsant agents to other medications.
• •10. The effects of belinostat on the developing human fetus are unknown. For this reason and because histone deacetylase inhibitors (HDAC) inhibitors as well as other therapeutic agents used in this trial 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. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• •11. Ability to understand and the willingness to sign a written informed consent document.
• •Inclusion of Women and Minorities
• •Both men and women of all races and ethnic groups are eligible for this trial