Sirolimus With Cyclophosphamide and Topotecan for Pediatric/Adolescent Relapsed and Refractory Solid Tumors

Inclusion Criteria: * Age: Patients must be \> than 12 months and 30 years of age at the time of study enrollment. * Diagnosis: Patients must have had histologic verification of solid tumor, including lymphomas, at original diagnosis or relapse except in patients with intrinsic brain stem tumors, patients with optic pathway gliomas, and patients with pineal tumors and elevations of serum or CSF alpha-fetoprotein or beta-HCG. * Disease Status: Patients must have either measurable or evaluable disease * Therapeutic Options: Patient's current disease state must be one for which there is no known curative therapy. * Performance Level: Karnofsky 50% for patients \> 16 years of age and Lansky 50 for patients 16 years of age. Note: Neurologic deficits in patients with CNS tumors must have been relatively stable for a minimum of 1 week prior to study enrollment. 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. (Appendix I) * Prior Therapy: Patients must have fully recovered from the acute toxic effects of all prior anticancer chemotherapy. * Myelosuppressive chemotherapy: Patients must not have received myelosuppressive therapy within 2 weeks of enrollment onto this study (6 weeks if prior nitrosourea). * Hematopoietic growth factors: At least 14 days after the last dose of a long-acting growth factor (e.g. Neulasta) 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. * Biologic (anti-neoplastic agent): At least 7 days must have passed after the last treatment with a biologic agent. For agents that have known adverse events occurring beyond 7 days from 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. * Immunotherapy: At least 4 weeks since the completion of any type of immunotherapy, e.g. tumor vaccines. * Monoclonal antibodies: At least 7 days or 3 half-lives, whichever is longer, must have elapsed since prior treatment with a monoclonal antibody. Please see Appendix III for a list of half-lives for common monoclonal antibodies. * XRT: ≥ 2 weeks must have elapsed for local palliative XRT (small port) and enrollment on study. At least 24 weeks must have elapsed since prior Total Body Irradiation (TBI), radiation to ≥50% of pelvis, or craniospinal radiation; ≥ 6 weeks must have elapsed if the patient has received other substantial BM radiation; \> 6 weeks for prior MIBG therapy; For patients with only one site of measurable or evaluable disease, radiation must not have been given to that site unless that site has demonstrated clear progression after radiation or at least 2 months have elapsed since radiation and their remains evidence of viable tumor on biopsy, FDG pet scan or MIBG scan. * Stem Cell Transplant (SCT): Patients are eligible 12 weeks after myeloablative therapy with autologous stem cell transplant (timed from start of protocol therapy). Patients must meet adequate bone marrow function definition (see organ function requirements below) post-myeloablative therapy. Patients who received stem cell reinfusion following non-myeloablative therapy are eligible once they meet peripheral blood count criteria in 6.1.7.1 Patients status post-allogeneic stem cell transplant are excluded unless they are \>1 year post transplant, have been off all immunosuppressive therapy for more than 3 months and do not have active GVHD. * Prior treatment with sirolimus, cyclophosphamide or topotecan: Patients previously treated with any of these drugs as single agents will be eligible for this study. Patients previously treated with two of the three drugs will also be eligible, however patients previously treated with all three agents in combination will not be eligible. * Patients previously treated with sirolimus analogues (e.g. Temsirolimus, everolimus, or ridaforolimus) are also eligible. Organ Function Requirements * Adequate Bone Marrow Function Defined as: * For patients with solid tumors without bone marrow involvement: * Peripheral absolute neutrophil count (ANC) 750/L * Platelet count 75,000/L (transfusion independent, defined as not receiving platelet transfusions within a 7 day period prior to enrollment) * Patients with known bone marrow metastatic disease: * Peripheral absolute neutrophil count (AND) ≥ 750/L * Platelet count ≥ 25,000/L Transfusions are permitted to reach the platelet criteria. These patients will not be evaluable for hematologic toxicity and must not be known to be refractory to platelet transfusions. At least two thirds (2 of 3 or 4 of 6) of every cohort must be evaluable for hematologic toxicity. Adequate Liver Function Defined as: * Bilirubin (sum of conjugated + unconjugated) 1.5 x upper limit of normal (ULN) for age * SGPT (ALT) 110 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L. * Serum albumin 2 g/dL Adequate Pulmonary Function Defined as: * No dyspnea at rest * No known requirement for supplemental oxygen * No known active pneumonitis Central Nervous System Function Defined as: * Patients with seizure disorder may be enrolled if on non-enzyme inducing anticonvulsants and if seizures are well controlled. (See Appendix IV for a list of recommended non-enzyme inducing anticonvulsants). * Nervous system disorders(CTCAE v4) resulting from prior therapy must be ≤ Grade 2. * Serum fasting triglyceride level ≤ 300 mg/dL (≤ 3.42 mmol/L) and serum cholesterol level ≤ 300 mg/dL (≤7.75 mmol/L) Exclusion Criteria: * Pregnancy or Breast-Feeding: Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method. * Concomitant Medications: * Corticosteroids: Patients requiring corticosteroids who have not been on a stable or decreasing dose of corticosteroid for the prior 7 days. * Anti-cancer Agents: Patients who are currently receiving other anti-cancer agents are not eligible. * Enzyme-inducing anticonvulsants: Patients who are currently receiving enzyme inducing anticonvulsants are not eligible. * CYP3A4 active agents: Patients must not be receiving any of the following potent CYP3A4 inducers or inhibitors: erythromycin, clarithromycin, ketoconazole, azithromycin, itraconazole, grapefruit juice or St. John's Wort. A list of other known CYP3A4 inducers and inhibitors that should be avoided during study therapy is included in Appendix V. * Infection: Patients who have an active or uncontrolled infection are not eligible. Patients on prolonged antifungal therapy are still eligible if they are culture and biopsy negative in suspected radiographic lesions and meet other organ function criteria. Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible. * Patients with history of allergic reactions attributed to compounds of similar composition to sirolimus, cyclophosphamide, or topotecan are not eligible.