Phase I Study to Assess the Safety, Tolerability and Pharmacokinetics of CUDC-427 When Given to Patients With Advanced and Refractory Solid Tumors or Lymphoma

Exclusion Criteria

• •Systemic anticancer therapy within 3 weeks of study entry, except for nitrosoureas or mitomycin C (6 weeks). Subjects with prostate cancer receiving luteinizing hormone-releasing hormone (LHRH) hormonal therapy may be enrolled and continue on this therapy.
• •Other investigational agents within 21 days prior to the first dose of study drug.
• •Prior treatment with an antagonist of inhibitors of apoptosis proteins.
• •History of chronic liver disease, hepatic cirrhosis, current cholestatic disease, active hepatic infection, non-alcoholic steatohepatitis (NASH), current alcohol or substance abuse (liver metastases due to disease under study are permitted).
• •Pregnant or lactating/breast-feeding women.
• •Ongoing treatment with chronic immunosuppressants.
• •Known gastrointestinal condition that would interfere with swallowing or the oral absorption or tolerance of CUDC-427.
• •Ongoing diarrhea defined as more than 1 watery stool/day.
• •Infection requiring intravenous antibiotic therapy within 14 days prior to the first dose of study drug.
• •Clinically significant cardiac history, such as:
• •* Uncontrolled or severe cardiovascular disease, including myocardial infarct or unstable angina within 6 months prior to study treatment, New York Heart Association (NYHA) Class II or greater congestive heart failure, serious arrhythmias requiring medication for treatment, clinically significant pericardial disease, or cardiac amyloidosis.
• •* Previous history of QTc prolongation as a result of other medication that required discontinuation of that medication.
• •* Congenital long QT syndrome or first degree relative with unexplained sudden death under 40 years of age.
• •* QTc with Fridericia's (QTcF) correction that is unmeasurable or ≥ 480 msec on screening ECG. If a subject has a QTcF ≥ 480 sec on the screening ECG, the ECG may be repeated twice (at least 24 hour apart) and the mean QTcF from the three screening ECGs must be \< 480 msec in order for the subject to be eligible for the study.
• •* Ejection fraction (EF) by ECHO \< 55% (abnormal values may be repeated x2 and the mean of the 3 tests used for determination)
• •* Use of any concomitant medication (within 7 days of starting treatment) that may cause QTc prolongation, inducing Torsades de Pointes
• •Unstable or clinically significant concurrent medical condition that would, in the opinion of the investigator, jeopardize the safety of a subject and/or their compliance with the protocol.
• •Known human immunodeficiency virus (HIV) positive.
• •Prior malignancy within 2 years except non-melanoma skin cancer and other in situ carcinomas that have been surgically treated with curative intent.