['breast neoplasms', 'lung neoplasms', 'cancer of liver', 'lymphoma', 'cancer of kidney']
['metformin xr', 'delayed metformin', 'sirolimus']

        Inclusion Criteria

          1. Histologically or cytologically confirmed solid tumor that is metastatic or
             unresectable and for which standard curative or palliative measures do not exist or
             are no longer effective.

          2. ECOG performance status 0 or 1 (See Appendix B).

          3. Age ≥ 18 years.

          4. Non-pregnant, non-lactating women using adequate contraception.

          5. Ability to understand and willingness to sign informed consent.

          6. Adequate hematologic, renal and hepatic function, as defined by each of the following:

               -  Absolute neutrophil count (ANC) > l500/μl

               -  Platelets > 100,000/μl

               -  Total bilirubin < 1.5 x upper limit of normal

               -  SGOT and SGPT < 2.5x upper limit of normal for patients without liver metastases
                  or SGOT and

               -  SGPT < 5 x upper limit of normal for patients with liver metastases.

               -  Creatinine < 1.4 mg/dl for females or < 1.5 mg/dl for males.

          7. Prior treatment with mTOR inhibitors will be allowed as long as the patient did not
             have ≥ Grade 3 toxicity attributed to the mTOR inhibitor with prior therapy.

          8. Measurable or non-measurable disease will be allowed.

          9. Patients taking substrates, inhibitors, or inducers of CYP3A4 (See Appendix C) should
             be encouraged to switch to alternative drugs whenever possible, given the potential
             for drug-drug interactions with sirolimus.

        Exclusion Criteria

          1. Prior treatment with an mTOR inhibitor (including sirolimus) is allowed; however,
             patients with ≥ grade 3 toxicities with an mTOR inhibitor are excluded.

          2. Fasting glucose > 200 mg/dL or fasting triglycerides > 300 mg/dL.

          3. Patients who have had chemotherapy or immunotherapy within 4 weeks of starting study
             drug, or radiotherapy within 14 days of starting study drug, or those who have not
             recovered from adverse events due to agents administered more than 4 weeks earlier.

          4. Patients may not be receiving any other investigational agents or any concomitant
             antineoplastic therapy, with the exceptions of octreotide LAR (for neuroendocrine
             tumors) and endocrine therapy (for prostate, breast, or gynecologic malignancies).

          5. Serious underlying medical (including acute decompensated congestive heart failure) or
             psychiatric illnesses that would, in the opinion of the treating physician,
             substantially increase the risk for complications related to treatment. Similarly, any
             unstable medical condition that, in the opinion of the treating physician or study
             investigators, would interfere with the study objectives.

          6. Pregnancy or breastfeeding.

          7. Major surgery within 4 weeks.

          8. Concurrent use of any proton pump inhibitors, as these limit the absorption of
             metformin30,41.

          9. History of lactic acidosis as per prior medical records or provided by the patient.

         10. Metabolic acidosis, acute or chronic. Acidosis will be defined a blood pH < 7.35.
             Acidosis will be suspected if serum bicarbonate is < 22 mEq/L. In such cases, venous
             blood pH would be checked to confirm or exclude acidosis.

         11. Participants with known uncontrolled diabetes, defined as a hemoglobin A1C of > 8%.

         12. Participants who are already on treatment with metformin, except when metformin can be
             held for 4 weeks prior to the start of the study.

         13. History of ongoing alcohol abuse or binge drinking. Alcohol abuse will be defined as a
             pattern of drinking that results in harm to one's health, interpersonal relationships,
             and ability to work. Binge drinking will be defined as at least one episode of
             consuming more than five units in men and four units in women during the previous
             month. One unit of alcohol can generally said to be a half pint of beer, a single
             measure (shot glass) of a spirit or a small glass of table wine.
      