Study of MLN4924 in Adult Patients With Nonhematologic Malignancies

Exclusion Criteria

• •Pregnant or lactating
• •Major surgery within 14 days prior to the first dose of study treatment
• •Serious infection within 14 days prior to the first dose of study treatment
• •Receiving antibiotic therapy within 14 days prior to the first dose of study treatment
• •Life-threatening illness unrelated to cancer
• •Diarrhea that is greater than Grade 1 in severity
• •Systemic antineoplastic therapy within 21 days preceding first dose of study treatment
• •Radiotherapy within 21 days preceding first dose of study treatment
• •Prior treatment with radiation therapy involving ≥25% of the hematopoietically active bone marrow
• •CYP3A inducers within 14 days before the first dose of MLN4924. Moderate and strong CYP3A inhibitors and CYP3A inducers are not permitted during the study.
• •Clinically significant central nervous system metastases
• •Absolute neutrophil count \<1,500/mm3; platelet count \<100,000/mm3
• •Patients with a prothrombin time or aPTT \> 1.5 x the upper limit of the normal range, or with a history of a coagulopathy or bleeding disorder
• •Ongoing anti-coagulant therapy that can not be held to permit tumor biopsy
• •Calculated creatinine clearance \<50 mL/minute
• •Bilirubin \>1.5 times the upper limit of normal; aspartate aminotransferase, alanine aminotransferase, or alkaline phosphatase \>2.5 times the upper limit of normal.
• •Uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure, angina, or myocardial infarction within the past 6 months
• •Abnormalities on 12-lead electrocardiogram including, but not limited to, changes in rhythm and intervals that in the opinion of the investigator are considered to be clinically significant
• •Known human immunodeficiency virus positive or hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection
• •Treatment with any investigational products within 28 days preceding the first dose of study treatment