This study aims to determine the efficacy of daily sirolimus and celecoxib, with low dose etoposide alternating with cyclophosphamide for pediatric participants with relapsed or refractory tumors.

This study aims to learn if the combination of oral sirolimus once daily with celecoxib, and with oral etoposide alternating every 21 days with oral cyclophosphamide (metronomic chemotherapy) is effective in shrinking relapsed or refractory tumors in pediatric participants. In addition, this study seeks to learn the length of time this combination can keep the tumor from growing, learn more about the side effects of sirolimus when used in this combination, and to learn if the sirolimus is working by evaluating blood and tumor tissue.

Inclusion Criteria:

• Participants with any of the following tumors who have experienced relapse following front-line therapy, or who are refractory to front-line therapy, and participants with tumors that carry a poor prognosis and have no known standard curative therapy

  • Brain tumors of all World Health Organization (WHO) grades, except diffuse intrinsic pontine glioma (DIPG) - enrollment in the brain tumor stratum is closed
  • Extracranial solid tumors including histiocytoses

• Participants must have had a histologic verification of malignancy at original diagnosis or relapse, except in participants with optic pathway gliomas, or participants with pineal tumors and elevations of serum or cerebrospinal fluid (CSF) alpha-fetoprotein (AFP) or beta-human chorionic gonadotropin (beta-HCG)

• Tissue blocks or slides must be sent

• Participants must have radiographically measurable disease at the time of study enrollment to be eligible. Patients with neuroblastoma who do not have measurable disease but have metaiodobenzylguanidine (MIBG+) evaluable disease are eligible. Measurable disease in patients with CNS involvement is defined as tumor that is measurable (≥ 10 mm) in two perpendicular diameters on MRI and visible on more than one slice. For all patients, tumors that are located in a previously irradiated area may be considered measurable if the lesion has shown tumor growth after radiation or has been biopsied and proven to have active disease.

• Participant's current disease state must be one for which there is no known curative therapy

• Karnofsky performance level of greater than or equal to 50 percent for participants who are greater than 16 years of age at the time of screening

• Lansky performance level of greater than or equal to 50 percent for participants who are less than or equal to 16 years of age at the time of screening

• Fully recovered from acute toxic effects of all prior anti-cancer therapy

• Adequate bone marrow function as deemed by the protocol at the time of screening

• Adequate renal function as deemed by the study protocol at the time of screening

• Adequate liver function as deemed by the study protocol at the time of screening

• Serum triglyceride level ≤300 mg/dL and serum cholesterol ≤ 300 mg/dL

• Random or fasting blood glucose within the upper normal limits for age

• Adequate pulmonary function as deemed by the study protocol at the time of screening

Exclusion Criteria:

• Women who are currently pregnant or breastfeeding
• Receiving corticosteroids who have not been on a stable dose for at least 7 days
• Currently receiving enzyme inducing anticonvulsants
• Currently receiving receiving potent CYP3A4 (enzyme) inducers or inhibitors
• Currently receiving another investigational drug
• Currently receiving any other anti-cancer agents
• The use of cannabis oil is prohibited during the first 2 cycles of this protocol. Patients must be off of cannabis oil for 3 days prior to enrollment.
• Uncontrolled infection
• Participants who in the opinion of the investigator may not be able to comply with the safety monitoring requirements