A Open Label Phase I/II Clinical Trial to Evaluate CPI-613 in Patients With Advanced Malignancies

Exclusion Criteria

• •Serious medical illness, such as significant cardiac disease (symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, uncontrolled cardiac arrhythmia, or New York Heart Association Class III or IV), or severe debilitating pulmonary disease, that would potentially increase patients' risk for toxicity.
• •Patients with active central nervous system (CNS) or epidural tumor.
• •Any active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g., active peptic ulcer disease).
• •Pregnant women, or women of child-bearing potential not using reliable means of contraception (because the teratogenic potential of CPI-613 is unknown).
• •Lactating females because the potential of excretion of CPI-613 into breast milk. (Note: Lactating females are excluded because the effects of CPI-613 on a nursing child are unknown.)
• •Fertile men unwilling to practice contraceptive methods during the study period.
• •Life expectancy less than 3 months.
• •Any condition or abnormality which may, in the opinion of the investigator, compromise the safety of patients.
• •Unwilling or unable to follow protocol requirements.
• •Dyspnea with minimal to moderate exertion. Patients with large and recurrent pleural, or peritoneal effusions requiring frequent drainage (e.g. weekly). Patients with any amount of clinically significant pericardial effusion.
• •Active heart disease including myocardial infarction within previous 6 months, symptomatic coronary artery disease, arrhythmias requiring medication, or symptomatic congestive heart failure.
• •Albumin \<2.5 g/dL or \<25 g/L.
• •Evidence of active infection, or serious infection within the past month.
• •Patients with known HIV infection.
• •Patients receiving any other standard or investigational treatment for their cancer, or any other investigational agent for any indication within the past 3 weeks prior to initiation of CPI-613 treatment.
• •Patients who have received immunotherapy of any type within the past 4 weeks prior to initiation of CPI-613 treatment.
• •Requirement for immediate palliative treatment of any kind including surgery.
• •Patients that have received a chemotherapy regimen with stem cell support in the previous 6 months.
• •A marked baseline prolongation of QT/QTc interval (e.g., repeated exhibition of a QTc interval \>470 ms.).
• •A history of additional risk factors for torsade de pointes (e.g., clinically significant heart failure, hypokalemia, family history of Long QT Syndrome).
• •Troponin I above institution limit of normal or Left Ventricular Ejection Fraction (LVEF) below 35%.