A Phase I Study of the Safety, Pharmacokinetics, and Anti-Tumor Activity of CUDC-101 in Patients With Advanced Solid Tumors

Inclusion criteria

• Subjects with advanced, refractory solid tumors and a histopathologically confirmed diagnosis
• Subjects must have no further standard of care options or have refused standard therapy
• Measurable or evaluable disease
• Age ≥ 18 years
• ECOG performance < 2
• Life expectancy ≥ 3 months
• If female, neither pregnant or lactating
• If of child bearing potential, must use adequate birth control
• Absolute neutrophil count ≥ 1,500/µL; platelets ≥ 100,000/µL;
• Creatinine ≤ 1.5x upper limit of normal (ULN) or calculated creatinine clearance ≥ 60mL/min/1.73m2
• Total bilirubin ≤ 1.5x ULN; AST/ALT ≤ 2.5x ULN. In subjects with documented liver metastases, the AST/ALT may be ≤ 5x ULN
• Prothrombin time ≤1.5x ULN, unless receiving therapeutic anticoagulation
• Serum magnesium and potassium within normal limits (may be supplement to achieve normal values)
• Subjects with brain metastases are eligible if controlled on a stable dose ≤ 10mg prednisone/day or its equivalent dose of steroids
• Able to render informed consent and to follow protocol requirements.

Exclusion criteria

• Anticancer therapy within 4 weeks of study entry. Prostate cancer subjects on LHRH hormonal therapy may be enrolled and continue on this therapy.
• Use of investigational agent(s) within 30 days of study entry
• History of cardiac disease with a New York Heart Association (NYHA) Class II or greater congestive heart failure (CHF), myocardial infarction (MI) or unstable angina in the past 6 months prior to Day 1 of treatment, serious arrhythmias requiring medication for treatment.
• Known infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C.
• The following are permitted but should be used with caution and other suitable agents used if possible:

• Subjects receiving concomitant medications metabolized by CYP 3A4 and CYP 2D6
• CYP3A4 inducers
• CYP3A4 inhibitors
• Warfarin