Temsirolimus in Combination With Metformin in Patients With Advanced Cancers

Inclusion Criteria:

1. Patients with advanced or metastatic cancer that is refractory to standard therapies, who have relapsed after standard therapy, or whose cancers have no standard therapy that induces a complete response (CR) rate of at least 10% or improves survival by at least three months.
2. Patients must have evaluable or measurable disease by RECIST criteria.
3. Patients must be >/= 4 weeks beyond treatment of any chemotherapy, other investigational therapy, hormonal, biological, targeted agents or radiotherapy, and must have recovered to </= grade 1 or previous baseline for each toxicity. Exception: Patients may have received palliative low dose radiotherapy to the limbs 1-4 weeks before this therapy provided pelvis, sternum, scapulae, vertebrae, or skull were not included in the radiotherapy field. Patients who have received non-chemotherapeutic biological agents will need to wait at least 5 half-lives or 4 wks, whichever is shorter, from the last day of treatment.
4. Patients must be >/= 4 weeks beyond treatment with metformin and currently not taking metformin
5. Patients may be on antidiabetic treatment other than Metformin
6. ECOG performance status </= 2
7. Abnormal organ function is permitted. However, patients must have absolute neutrophil count >/= 1000/mL; platelets >/= 75,000/mL; creatinine < 1.5 mg/dl in males and < 1.4 in females;T. Bilirubin </= 3 X upper limit of normal (ULN); AST(SGOT) and/or ALT(SGPT) </= 5 X ULN
8. Women of child-bearing potential MUST have a negative serum or urine HCG test unless prior hysterectomy or menopause (defined as 12 consecutive months without menstrual activity). Patients should not become pregnant or breastfeed while on this study. Sexually active patients must agree to use contraception prior to study entry, for the duration of study participation, and for 30 days after the last dose
9. Ability to understand and willingness to sign a written informed consent document.
10. Patients must be >/= 14 years of age.
11. Patients in the expansion cohort must have any diagnosed molecular aberrations that activate the PI3K/mTOR or MEK pathways, including but not limited to alterations in one or more of the following genes: PTEN, BRAF, KRAS, NRAS, PI3KCA, ErbB1, ErbB2, MET, RET, c-KIT GNAQ, GNA11 and ALK.

Exclusion Criteria:

1. Patients who are pregnant or breastfeeding.
2. Uncontrolled intercurrent illness including, but not limited to, active infection requiring hospitalization.
3. History of hypersensitivity to temsirolimus or metformin.
4. History of CVA, myocardial infarction or unstable angina within the previous six months before starting therapy
5. New York Heart Association Class III or greater congestive heart failure.
6. Patients with major surgery within 30 days prior to entering the study.
7. Patients unable to swallow oral medications or with pre-existing gastrointestinal disorders that might interfere with proper absorption of oral drugs.