Study of MLN4924 in Adult Patients With Nonhematologic Malignancies

Inclusion criteria

• Male or female patients 18 years or older
• Eastern Cooperative Oncology Group performance status 0-2
• Patients must have a diagnosis of a nonhematologic malignancy for which standard curative, life-prolonging, or palliative treatment does not exist or is no longer effective.
• Expected survival longer than 6 weeks from enrollment in the study
• Radiographically or clinically evaluable tumor
• Suitable venous access for the conduct of blood sampling for MLN4924
• Tumor tissue that, in the opinion of the investigator, can be safely biopsied using a core needle
• Male patients must use an appropriate method of barrier contraception
• Female patients must be postmenopausal, surgically sterilized, or willing to use reliable methods of birth control
• Voluntary written consent

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