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

- Extracranial solid tumors including neuroblastoma

- Bone tumors (osteosarcoma, Ewing sarcoma)

- Rhabdomyosarcoma

- Soft tissue sarcomas

- Wilms tumor

- Other rare solid tumors

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

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

- Lansky performance level of greater than or equal to 50 percent for participants 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

- 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

- Uncontrolled infection

- Participants who in the opinion of the investigator may not be able to comply with the
safety monitoring requirements