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