Phase IB Metformin, Digoxin, Simvastatin in Solid Tumors

Inclusion Criteria

1. Subject ≥18 years with histologically confirmed solid tumor.

2. Dose expansion subjects must have at least one tumor mass amenable to core needlebiopsy.

3. Refractory or intolerant to established standard of care.

4. Have at least one tumor mass amenable to core needle biopsy. Adequate ArchivalTissue required for patients that will take part in the dose escalation cohorts.

5. ECOG performance status (PS) = 0-2, or Karnofsky PS ≥60%, or Lansky PS ≥60%.

6. Normal organ and marrow function: absolute granulocyte count ≥1,000/mm3, absolutelymphocyte count ≥400/mm3, platelets ≥100,000/mm3, total bilirubin ≤ institutionalupper normal limit, AST/ASL ≤2x institutional upper limit of normal, GFR >60mL/min/1.73 m2 and creatinine <1.5 mg/dL.

7. Subject has recovered to CTCAE Grade 1 or better from all adverse events associatedwith prior therapy or surgery. Pre-existing motor or sensory neurologic pathology orsymptoms must be recovered to CTCAE Grade 2 or better.

8. If female 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 serumtest will then be required for study entry.

9. Ability to understand and the willingness to sign a written informed protocolspecific consent.

Exclusion Criteria:

1. Anti-cancer chemotherapy, biologic therapy or immunotherapy within 3 weeks orradiation therapy within 2 weeks of first infusion.

2. Known history of other malignancy unless having undergone curative intent therapywithout evidence of that disease for ≥ 3 years except cutaneous squamous cell andbasal cell skin cancer, superficial bladder cancer, in situ cervical cancer or otherin situ cancers are allowed if definitively resected.

3. Patients with only PET non-avid disease.

4. Brain metastases unless treated with curative intent (gamma knife or surgicalresection) and without evidence of progression for ≥ 2 months.

5. Known history of rhabdomyolysis.

6. History of or current evidence of any condition (including medical, psychiatric orsubstance abuse disorder), therapy, or laboratory abnormality that might confoundthe results of the study, interfere with the subject's participation for the fullduration of the study, or is not in the best interest of the subject to participate,in the opinion of the Investigator.

7. Known HIV or chronic Hepatitis B or C infection.

8. Have signs and symptoms consistent with an active infection.

9. Live vaccination for the prevention of infectious disease administered <30 daysprior to the start of study therapy or inactivated vaccination <14 days prior to thestart of study therapy.

10. History of severe allergic, anaphylactic, or other hypersensitivity reactions toMetformin, Simvastatin, and/or Digoxin.

11. Patients diagnosed with Wolff-Parkinson-White Syndrome or electrocardiographic (ECG)pattern. Other cardiac conditions including: Previous MI with evidence of residualelectrographic pattern consisted with bradycardia/heart block. Atrio-ventricular (AV) heart block (currently ongoing). History of ventricular fibrillation. SickSinus Syndrome or Sinus bradycardia thought to be caused by sinus node disease,unless effectively treated. Heart failure associated with preserved left ventricularejection fraction, including constructive pericarditis, restrictive cardiomyopathy,and Amyloid heart muscle disease.

12. Women of childbearing potential who are found to be pregnant as evidenced bypositive serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units ofHCG) or nursing.