1. Signed written informed consent
2. Patients must have histologic evidence of adenocarcinoma of the pancreas, such as a core tissue biopsy or a surgical resection specimen.
a. Cytological evidence only is not sufficient for enrollment on this study and patients can undergo a core tissue biopsy to meet this study enrollment criterion.
3. Patients must have metastatic disease. Baseline imaging of chest, abdomen and pelvis (CT or MRI) within 21 days prior to initiation of protocol therapy is required.
1. Patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
2. Patients with locally advanced unresectable pancreatic ductal adenocarcinoma are excluded.
4. Patients are allowed to have up to one prior line of systemic therapy in the adjuvant setting ONLY. No prior systemic therapy in the metastatic or locally advanced/unresectable setting is allowed. Toxicities related to prior therapy must have completely resolved (except for alopecia and anemia), or be deemed irreversible.
1. Patients who received Gemcitabine-based therapy in an adjuvant setting will be allowed to be enrolled on the trial as long as their last Gemcitabine administration was at least 6 months prior to the first dose of BBI608.
2. Prior treatment with radiotherapy is allowed.
5. = 18 years of age.
6. Patients must have an Eastern Cooperative Oncology Group (ECOG) Performance Status < 1.
7. Male or female patients of child-producing potential agree to use contraception or avoidance of pregnancy measures during the study and for 30 days after the last BBI608 dose.
8. Females of childbearing potential have a negative serum pregnancy test (preceding 72 hours of first day of BBI608 treatment).
9. Patients with biliary or gastro-duodenal obstruction must have drainage or surgical bypass prior to starting chemotherapy.
10. Significant or symptomatic amount of ascites should be drained prior to first dose of BBI608.
11. Patients on Coumadin anticoagulation may be enrolled for as long as they undergo weekly international normalized ratio (INR) checks for the first 2 months of therapy.
a. Patients who switch to low molecular weight heparin may be enrolled and weekly INR labs are not mandated for these patients.
12. Aspartate transaminase (AST) level < 2.5 x upper limit of normal (ULN) and alanine transaminase (ALT) < 2.5 × upper limit of normal (ULN). For patients with liver metastases, AST < 5 ULN, and AST < 5 ULN may be enrolled if agreed upon by the investigator and medical monitor for the sponsor.
13. Patients must have a total bilirubin level < 1.5 x ULN (= 2 x ULN if it is non-rising for a period of 10 days prior to initiation of therapy)
14. Creatinine level < 1.0 x ULN or creatinine clearance > 60 mL/min/1.73 m^2 for patients with creatinine levels above or below the institutional normal (as determined by Cockcroft-Gault equation). For patients with a Body Mass Index (BMI) > 30 kg/m^2, lean body weight should be used to calculate the glomerular filtration rate (GFR).
15. Hemoglobin (Hgb) = 9 g/dl
16. Absolute neutrophil count = 1.5 x 10^9/L
17. Platelets = 100 x 10^9/L
18. Acceptable coagulation studies as demonstrated by prothrombin time (PT) and partial thromboplastin time (PTT) within normal limits (+/-15%).
19. Patient has no clinically significant abnormalities on urinalysis results.
20. Life expectancy estimated at = 3 months.
1. Anti-cancer chemotherapy, radiotherapy, immunotherapy, or investigational agents within 14 days of the first dose of BBI608. Patients may begin BBI608 on a date determined by the investigator and medical monitor for the sponsor after a minimum of 14 days since last receiving anti-cancer treatment, provided that all treatment-related adverse events have resolved or have been deemed irreversible.
2. Patients with islet cell neoplasms will be excluded.
3. Major surgery, other than diagnostic surgery (e.g., surgery done to obtain a biopsy for diagnosis without removal of an organ), within 4 weeks prior to first dose.
4. Any brain metastases including leptomeningeal metastases, are excluded, even if treated and stable.
5. History of posterior reversible encephalopathy syndrome.
6. Neurosensory neuropathy = grade 2 at baseline.
7. Pregnant or breastfeeding.
8. Significant gastrointestinal disorder(s) that would, in the opinion of the Principal Investigator, prevent absorption of an orally available agent (e.g., Crohn's disease, ulcerative colitis, extensive gastric resection and small intestinal resection).
9. Unable or unwilling to swallow BBI608 capsules daily.
10. Uncontrolled chronic diarrhea = grade 2 at baseline.
11. Uncontrolled intercurrent illness including, but not limited to uncontrolled active infection (including bacterial, viral or fungal requiring systemic therapy), clinically significant non-healing or healing wounds, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, significant pulmonary disease (shortness of breath at rest or mild exertion), uncontrolled infection or psychiatric illness/social situations that would limit compliance with study requirements.
12. Known infection with Human Immunodeficiency Virus (HIV), and/or active infection with hepatitis B, or hepatitis C.
13. Significant cardiac disease, including the following: unstable angina, New York Heart Association class III-IV congestive heart failure, myocardial infarction within six months prior to study enrollment.
14. History of active Peripheral Artery Disease (treated peripheral artery disease that is stable for at least 6 months is allowed).
15. Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung.
16. History of hemolytic-uremic syndrome.
17. History of other active malignancies.
18. Known hypersensitivity to Gemcitabine or taxanes.
a. Patients with history of Gemcitabine toxicity in the adjuvant setting requiring more than 1 dose level reduction (as per Dose Modification schema described in Section 8.2.2) are excluded.
19. Prior treatment with BBI608.
20. Enrollment on any additional investigational agent study. Enrollment on concurrent observational study is allowed following consultation with the Sponsor.
21. Patients planning to take a vacation for 7 or more consecutive days during the course of the study.