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 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 10 years old, and Lansky ≥
50 for patients ≤ 10 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 patients' 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.