A Study of MLN0264 in Patients With Pancreatic Cancer

Inclusion Criteria: 1. Male or female participants 18 years of age or older when written informed consent is obtained. 2. Histologically confirmed metastatic or advanced inoperable adenocarcinoma of the pancreas with immunohistochemistry (IHC) evidence of guanylyl cyclase C (GCC) expression indicated by an H-score of 10 or greater. 3. Treatment with 1 or more prior chemotherapies for advanced or metastatic adenocarcinoma of the pancreas. 4. Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 guidelines. All scans and x-rays used to document measurable disease must be done within 28 days before enrollment (ascites and bone lesions are not considered measureable disease). 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 14 days before enrollment. 6. Female participants who: * Are postmenopausal for at least 1 year before the screening visit, OR * Are surgically sterile, OR * If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 30 days after the last dose of study drug, or * Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence \[eg, calendar, ovulation, symptothermal, postovulation methods\] and withdrawal are not acceptable methods of contraception.) Male participants, even if surgically sterilized (ie, status postvasectomy), who: * Agree to practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug, or * Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence \[eg, calendar, ovulation, symptothermal, postovulation methods for the female partner\] and withdrawal are not acceptable methods of contraception.) 7. Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care. 8. Adequate organ and hematological function as evidenced by the following laboratory values within 14 days before enrollment: * Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L * Platelet count ≥ 100 x 10\^9/L * Hemoglobin ≥ 9 g/dL * Activated partial thromboplastin time (aPTT) ≤ 1.5 x the upper limit of the normal range (ULN) per institutional laboratory normal range * International normalized ratio (INR) ≤ 1.5 x ULN * Serum creatinine ≤ 1.5 x ULN * Total bilirubin ≤ 1.5 x ULN * Albumin ≥ 3g/dL * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN * Serum lipase ≤ 3 x ULN and serum amylase within the normal range 9. Resolution of all toxic effects of prior treatments except alopecia to Grade 0 or 1 by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. 10. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures. Exclusion Criteria: 1. Radiotherapy within 4 weeks before enrollment. 2. Concurrent treatment or treatment within 4 weeks of study entry with any other investigational agent or chemotherapy. 3. Female participants who are lactating and breastfeeding or have a positive pregnancy test during the Screening period. 4. Uncontrolled, clinically significant, symptomatic cardiovascular disease within 6 months before enrollment, including myocardial infarction, unstable angina, Grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or arrhythmias not controlled by outpatient medication. 5. Treatment with any medication that has a clinically relevant potential risk of prolonging the QT interval or inducing torsades de pointes that cannot be discontinued or switched to a different medication before starting study drug. 6. Participants with electrocardiogram (ECG) abnormalities considered by the investigator to be clinically significant, or repeated baseline prolongation of the rate-corrected QT interval (QTc). 7. Ongoing or clinically significant active infection as judged by the investigator. 8. Signs of peripheral neuropathy (PN) ≥ NCI CTCAE Grade 2. 9. Concomitant chemotherapy, hormonal therapy, immunotherapy, or any other form of cancer treatment. 10. Use of strong cytochrome P450 (CYP) 3A4 inhibitors within 2 weeks before the first dose of study drug. 11. Any preexisting medical condition of sufficient severity to prevent full compliance with the study. 12. History of or current neoplasm other than gastric adenocarcinoma, except for curatively treated nonmelanoma skin cancer or in situ carcinoma of the cervix uteri. 13. Known diagnosis of human immunodeficiency virus (HIV) infection (testing is not mandatory). 14. Symptomatic brain metastases. 15. Ongoing anticoagulant therapy (eg, aspirin, coumadin, heparin).