Temsirolimus and Metformin Hydrochloride in Treating Patients with Advanced or Metastatic Cancer

Inclusion Criteria

• 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
• Patients must have evaluable or measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria
• 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 weeks (wks), whichever is shorter, from the last day of treatment; continuation of hormone replacement therapy is permitted; stable regimens of hormonal therapy i.e. for prostate cancer (e.g. leuprolide, a gonadotropin-releasing hormone [GnRH] agonist), ovarian, or breast cancer are not exclusionary
• Eastern Cooperative Oncology Group (ECOG) performance status =< 1
• Absolute neutrophil count >= 1000/mL
• Platelets >= 75,000/mL
• Creatinine < 1.5 mg/dl in males and < 1.4 in females
• Total (T.) bilirubin =< 3 X upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and/or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2 X ULN (=< 5 X ULN for patients with liver and/or bone metastases)
• Women of child-bearing potential MUST have a negative serum or urine pregnancy 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
• Ability to understand and willingness to sign a written informed consent document
• Patients in the tumor-specific endometrial carcinoma expansion cohort that have known mutation must be willing to provide consent for biopsies

Exclusion Criteria

• Patients who are pregnant or breastfeeding
• Uncontrolled intercurrent illness including, but not limited to, active infection requiring hospitalization
• History of hypersensitivity to temsirolimus or metformin
• History of cerebral vascular accident (CVA), myocardial infarction or unstable angina within the previous six months before starting therapy
• New York Heart Association class III or greater congestive heart failure
• Patients with major surgery within 30 days prior to entering the study
• Patients unable to swallow oral medications or with pre-existing gastrointestinal disorders that might interfere with proper absorption of oral drugs
• Patients on drugs that are strong cytochrome P450, family 3, subfamily A, polypeptide 4 (P450 CYP3A4) modifiers; these drugs should be stopped 5 half-lives prior to starting investigational agents with temsirolimus; the strong inducing or inhibiting agents should not restart until 1 week after the end of the study treatment; NOTE: we will allow replacement of steroids (with either prednisone or hydrocortisone) in patients with adrenalectomy
• Patients with a history of any grade of persistent or chronic nausea or vomiting within the last 4 weeks related to prior therapy or disease process