Metformin in Children With Relapsed or Refractory Solid Tumors

Inclusion Criteria: * Age: Patients must be \> 1 year of age and ≤ 18 years of age at time of initiation of protocol therapy. * Diagnosis: Patients have a histologically or radiographically confirmed relapsed or refractory solid tumor or primary central nervous system (CNS) malignancy. * Disease Status: Patients must have radiographically measurable disease. * Therapeutic Options: Patients must have relapsed or refractory cancers for which there is no known curative option or other available therapy proven to prolong survival with an acceptable quality of life. * Performance Level: Karnofsky ≥ 50% for patients older than 16 years old, and Lansky ≥ 50 for patients 1-16 years old. * Prior Therapy: Patients may have received prior therapy including vincristine, irinotecan, or temozolomide. Patients may not have previously been treated with combination therapy of irinotecan and temozolomide. * Patients must be fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study. * Myelosuppressive chemotherapy: Patients must not have received myelosuppressive chemotherapy within 3 weeks of starting protocol therapy, or a minimum of six weeks must have elapsed since prior nitrosurea chemotherapy. * Hematopoietic growth factor: At least 7 days must have elapsed since the last administration of filgrastim, or 14 days since administration of pegfilgrastim. * Biologic (anti-neoplastic agent): At least 7 must have elapsed since the last administration of any biologic agent. * Radiation therapy (XRT): At least 14 days since the last dose of local palliative radiation therapy. Greater than 6 months must have elapsed since the last day of treatment if given total body irradiation, craniospinal irradiation. * Autologous or Allogenic Stem Cell Transplant: Complete resolution of graft versus host disease and no current need for immunosuppressive medication. Greater than 3 months must have elapsed since engraftment and no longer requiring transfusion of platelets or injection of colony stimulating factors. * Organ Function Requirements * Bone Marrow Function: Peripheral absolute neutrophil count (ANC) ≥ 1000/μL; Platelet count ≥ 100,000/μL (no platelet transfusion within 7 days prior to obtaining laboratory result); Hemoglobin ≥ 8.0 gm/dL * Adequate Renal Function: Creatinine clearance or glomerular filtration rate ≥ 70ml/min/1.73m\^2 * Adequate Liver Function: Total bilirubin ≤ 1.5x upper limit of normal (ULN) for age; alanine transaminase (ALT) ≤ 5x ULN; Serum albumin ≥ 2gm/dL * Informed Consent: All patients ≥ 18 years of age must sign a written informed consent. For patients \< 18 years old, the patient's parents or legal guardians must sign a written informed consent, unless the patient is an emancipated minor. Childhood Assent, when age appropriate as per institutional guidelines, should be signed by the participating patient. Exclusion Criteria: * Significant organ dysfunction, not meeting inclusion criteria. * Pregnancy or Breast-Feeding woman will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies. * Concomitant Medications: * Growth factor: Growth factors that support platelet or white cell number of function must not have been administered within the past 7 days. * Steroids: Patients with CNS tumors who have not been on a stable or decreasing dose of dexamethasone for the past 7 days. * Investigational Drugs: Patients who are currently receiving another investigational drug. * Anti-cancer Agents: Patients who are currently receiving other anti-cancer agents. * Medication Allergy: Allergy or intolerance to agents on this protocol: vincristine, irinotecan, temozolomide, or metformin; Allergy to cephalosporins. * Infection: Patients who have uncontrolled infection, positive blood cultures within the past 48 hours, or receiving treatment for Clostridium difficile infection.