Inclusion Criteria:
1. Subject ≥18 years with histologically confirmed pancreatic cancer.
2. Refractory, intolerant to, or with disease progression after at least one standard of care regimen.
3. ECOG performance status (PS) 0-1.
4. Pretreatment biopsy and/or adequate archival tissue available for BIRC5 protein level evaluation.
5. Adequate organ and marrow function: absolute granulocyte count ≥1,000/mm3, platelets ≥100,000/mm3, total bilirubin ≤ institutional upper normal limit, AST/ALT ≤2x institutional upper limit of normal, and creatinine \<1.5 mg/dL or calculated creatinine clearance \> 60ml / min (Cockcroft-Gault Equation).
6. Subject has recovered to CTCAE Grade 1 (except for alopecia) or better from all adverse events associated with prior therapy or surgery. Pre-existing motor or sensory neurologic pathology or symptoms must be recovered to CTCAE Grade 2 or better.
7. If participant of childbearing potential, has a negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a negative serum test will be required for study entry. Serum pregnancy tests will be conducted at the time of screening, when other blood draws are obtained (See Appendix III: Time-Table of Procedures).
8. Ability to understand and the willingness to sign a written informed protocol specific consent.
9. Willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
10. No known active infections at the time of enrollment as determined by negative procalcitonin level.
Exclusion Criteria:
1. Anti-cancer chemotherapy, biologic therapy or immunotherapy within 3 weeks or radiation therapy within 2 weeks of first investigational product administration.
2. Known history of other malignancy unless having undergone curative intent therapy without evidence of that disease for ≥ 3 years except cutaneous squamous cell and basal cell skin cancer, superficial bladder cancer, in situ cervical cancer or other in situ cancers are allowed if definitively resected.
3. Brain metastases unless treated with curative intent (gamma knife or surgical resection) and without evidence of progression for ≥ 2 months.
4. Known history of rhabdomyolysis.
5. History of or current evidence of any condition (including medical, psychiatric or substance abuse disorder), therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the Investigator.
6. Known chronic Hepatitis B or C infection.
7. Have current active infection requiring systemic antibiotic treatment.
8. History of severe allergic, anaphylactic, hypersensitivity reactions or previous intolerance to Metformin, Simvastatin, and/or Digoxin.
9. Patients with significant cardiac disease or condition listed below (unless clearance obtained by cardiology):
1. Wolff-Parkinson-White Syndrome.
2. Previous MI within last 6 months of C1D1.
3. Evidence of residual electrographic pattern consistent with heart block., for example atrio-ventricular (AV) heart block (currently ongoing).
4. History of ventricular fibrillation.
5. Sick Sinus Syndrome or Sinus bradycardia thought to be caused by sinus node disease, unless effectively treated.
6. Heart failure with preserved LVEF, including constructive pericarditis, and amyloid heart disease.
10. Acute cor pulmonale, restrictive cardiomyopathy, and Amyloid heart muscle disease.
11. Participants of childbearing potential who are found to be pregnant as evidenced by positive serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) or nursing.
12. Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or trial results.
13. Cognitively impaired and diminished capacity.
