COZMOS: This phase I trial is testing a cancer drug that works by switching on genes to stop cancer growth, to see if it is a suitable treatment for children whose brain cancer has not responded to, or has gotten worse on, prior treatmentPhase I/Ib Trial of Combined 5'Azacitidine and Carboplatin for Recurrent/Refractory Pediatric Brain and Solid Tumors

Inclusion

1. Greater than the age of 1 year and under age 18 at the time of study enrolment
2. Recurrent or refractory brain or solid tumor, including recurrent or refractory ependymoma
3. Tissue from diagnosis or resection prior to registration must be available (either flash frozen tissue or an FFPE block)
4. Previous therapy with carboplatin will be permitted
5. Failed first line treatment (surgery, radiation therapy or chemotherapy) and should not be eligible for treatment with curative potential.
6. Be at least 4 weeks from the completion of myelosuppressive chemotherapy and/or biologic agents before starting day 1 of this study treatment
7. Be at least 14 days from the completion of radiation therapy and MIBG before starting day 1 of this study treatment
8. Be at least 3 months post hematopoetic stem cell rescue following myeloablative therapy before starting day 1 of this study treatment
9. Must have visible disease on imaging. Resection of visible disease is permitted while on study after two cycles including achievement of a gross total resection. If a resection is performed while on study, fresh frozen tissue should be submitted for analysis.
10. Concurrent medications will be limited to supportive medications/agents including but not limited to anti-emetics, steroids, analgesics and non-enzyme inducing anticonvulsants. Strong inducers of the P450 system will not be permitted. Other concurrent medications require approval of the study Sponsor.
11. Ability of the parent and/or child to understand and the willingness to sign a written informed consent document
12. Karnofsky ≥ 50 for patients > 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age (See Appendix I for the Karnofsky-Lansky Scores). Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score. Patients with posterior fossa syndrome/cerebellar mutism demonstrating clear improvement post-surgically can be enrolled based on physician discretion

13. Adequate hepatic, renal, marrow and cardiac function as defined below within 28 days prior to cycle 1 day 1:

    • Serum creatinine within normal institutional limits or creatinine clearance greater than 60mL/min
    • Serum bilirubin <1.5 times upper limit of institutional normal. Higher levels are acceptable if these can be attributed to active hemolysis or ineffective erythropoiesis
    • AST, ALT and Alkaline Phosphatase <3 times upper limit of institutional normal. If liver metastases are present, then <5 times upper limit of normal is permitted.
    • Normal QTc interval at screening ECG (baseline echocardiogram is not required)

    • Adequate marrow function defined below within 14 days prior to cycle 1 day 1:

      • Leukocytes greater than or equal to 1000 x106/L
      • Absolute neutrophil count greater than or equal to 0.75 x109/L
      • Platelets greater than or equal to 75 x109/L
      • Hemoglobin greater than or equal to 10g/dL (may be transfused).