Simvastatin With Topotecan and Cyclophosphamide in Relapsed and/or Refractory Pediatric Solid and CNS Tumors

Inclusion Criteria: * Subjects must have had histologic verification of malignancy at original diagnosis or relapse. All subjects with relapsed or refractory solid tumors are eligible including primary or metastatic CNS tumors. In the case of diffuse intrinsic pontine glioma (DIPG), or optic pathway glioma, imaging findings consistent with these tumors will suffice without the need for biopsy for histologic verification. * Subjects must have either measurable (the presence of at least one lesion that can be accurately measured in at least one dimension with the longest diameter at least 20 mm. With spiral CT scan, lesions must be at least 10 mm.) or evaluable disease (the presence of at least one lesion that cannot be accurately measured in at least one dimension. Such lesions may be evaluable by nuclear medicine techniques, immunocytochemistry techniques, tumor markers or other reliable measures.) * Subject's current disease state must be one for which there is no known curative therapy. * Karnofsky ≥ 60% for subjects \> 16 years of age and Lansky ≥ 50 for subjects ≤ 16 years of age * Subjects must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy 1. Myelosuppressive chemotherapy: At least 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea). 2. Hematopoietic growth factors: At least 14 days after the last dose of a long-acting growth factor (e.g. Pegfilgrastim) or 7 days for short acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair. 3. Biologic (anti-neoplastic agent): At least 7 days after the last dose of a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair. 4. Immunotherapy: At least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines. 5. Monoclonal antibodies: At least 3 half-lives of the antibody after the last dose of a monoclonal antibody. 6. external beam radiation therapy (XRT): At least 14 days after local palliative XRT (small port); 6 weeks must have elapsed since treatment with therapeutic doses of I131-meta-iodobenzylguanidine (MIBG); At least 150 days must have elapsed if prior total body irradiation (TBI), craniospinal XRT, or if ≥ 50% radiation of pelvis; At least 42 days must have elapsed if other substantial bone marrow (BM) radiation. 7. Stem Cell Infusion without TBI: No evidence of active graft vs. host disease and at least 84 days must have elapsed after transplant and 42 days for autologous stem cell infusion after I131-MIBG therapy. 8. Subjects must not have received any prior therapy with simvastatin. * Adequate Bone Marrow Function Defined as: 1. For subjects with solid tumors without known bone marrow involvement: Peripheral absolute neutrophil count (ANC) ≥ 750/mm3, Platelet count ≥ 75,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) 2. Subjects with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts in a. (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These subjects will not be evaluable for hematologic toxicity. If dose-limiting hematologic toxicity is observed, all subsequent subjects enrolled must be evaluable for hematologic toxicity. * Adequate Renal Function Defined as: 1. Creatinine clearance or radioisotope glomerular filtration rate (GFR) 70ml/min/1.73 m\^2 or 2. A serum creatinine based on age/gender as follows: * Age: 1 to \< 2 years; Male and female serum creatinine: 0.6 mg/dL * 2 to \< 6 years; Male and female serum creatinine: 0.8 mg/dL * 6 to \< 10 years; Male and female serum creatinine: 1.0 mg/dL * 10 to \< 13 years; Male and female serum creatinine: 1.2 mg/dL * 13 to \< 16 years; Male serum creatinine: 1.5 mg/dL and female serum creatinine: 1.4 mg/dL * ≥ 16 years; Male serum creatinine: 1.7 mg/dL and female serum creatinine: 1.4 mg/dL * Adequate Liver Function Defined as: 1. Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age 2. serum glutamate pyruvate transaminase (SGPT) or ALT ≤ 135 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L. * Adequate Cardiac Function Defined as: corrected QT interval (QTc) ≤ 480 msec * Normal Creatinine Phosphokinase (CPK) Defined As Not Exceeding Maximum Value: * Age: 0 to \< 4 years; Male and female maximum CPK : 305 units/L * 4 to \< 7 years; Male and female maximum CPK : 230 units/L * 7 to \< 10 years; Male and female maximum CPK : 365 units/L * 10 to \< 12 years; Male maximum CPK: 215 units/L and female maximum CPK: 230 units/L * 12 to \< 14 years; Male maximum CPK: 330 units/L and female maximum CPK: 295 units/L * 14 to \< 16 years; Male maximum CPK: 335 units/L and female maximum CPK: 240 units/L * 16 to \< 19 years; Male maximum CPK: 370 units/L and female maximum CPK: 230 units/L * ≥ 19 years; Male maximum CPK: 170 units/L and female maximum CPK: 145 units/L * Willing to sign consent or assent/primary caregiver willing to give consent Exclusion Criteria: * Pregnancy or breast-feeding * Concomitant medication dependency including corticosteroids, investigational drugs, anti-cancer agents, anti-graft-versus-host disease (GVHD) agents post-transplant * subjects who are unable to swallow a tablet or liquid must have a nasogastric (NG) or gastric (G) tube through which the medicine can be administered * subjects receiving known cytochrome P450 3A4 (CYP3A4) Inhibitors or Inducers * subjects with uncontrolled infection * subjects who received prior solid organ transplantation * subjects with current or previous treatment with 3-hydroxy-3-methylglutaryl-coenzyme A (HMG CoA) reductase inhibitor (any statin)