Sirolimus in Combination With Metronomic Chemotherapy in Children With Recurrent and/or Refractory Solid and CNS Tumors

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