Study: NCT02114229

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: alisertib
Description: Alisertib will be administered orally at 80 mg/m\^2 per day for enteric coated tablet formulation and 60 mg/m\^2 per day for oral solution formulation.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: alisertib
Description: Alisertib will be administered orally at 80 mg/m\^2 per day for enteric coated tablet formulation and 60 mg/m\^2 per day for oral solution formulation.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: alisertib
Description: Alisertib will be administered orally at 80 mg/m\^2 per day for enteric coated tablet formulation and 60 mg/m\^2 per day for oral solution formulation.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: methotrexate
Description: Methotrexate will be given at a dose of 5 g/m\^2/dose as an intravenous infusion over 24 hours on day 1 of each induction cycle except in patients ≤ 31 days of age at enrollment. These young infants will receive methotrexate at a reduced dose of 2.5g/m\^2/dose.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: cisplatin
Description: Cisplatin will be given intravenously (IV): 75 mg/m\^2 IV infusion.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: cisplatin
Description: Cisplatin will be given intravenously (IV): 75 mg/m\^2 IV infusion.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: carboplatin
Description: Carboplatin may be substituted for cisplatin during induction for patients having Grade 4 ototoxicity or bi-lateral hearing loss after having prior cisplatin dose reduction. Route of administration is IV.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: cyclophosphamide
Description: Cyclophosphamide will be given 1.5 g/m\^2 IV infusion during induction and consolidation.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: cyclophosphamide
Description: Cyclophosphamide will be given 1.5 g/m\^2 IV infusion during induction and consolidation.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: etoposide
Description: Etoposide will be given 100 mg/m\^2 IV infusion.~In case of etoposide reactions, etoposide phosphate will be given 40 mg/kg/day.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: topotecan
Description: Topotecan will be administered by intravenous infusion over 4 hours on days 1-5 of each consolidation cycle for Stratum B2 and B3 patients not receiving craniospinal irradiation. The initial dose of Topotecan will be based on patient's age with subsequent doses adjusted, if necessary, to achieve a topotecan lactone area under the curve (AUC) of 140 ± 20 ng/mL\*hr.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: vincristine
Description: Vincristine will be given 1 mg/m\^2 IV via 25 mL normal saline (NS) mini-bag (maximum 2 mg for all patients) or administration per local institutional standards for participating sites.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: vincristine
Description: Vincristine will be given 1 mg/m\^2 IV via 25 mL normal saline (NS) mini-bag (maximum 2 mg for all patients) or administration per local institutional standards for participating sites.

Intervention type: PROCEDURE
Group type: EXPERIMENTAL
Intervention: Surgical resection
Description: For patients with localized AT/RT, gross total resection results in a significant survival benefit. Maximal resection that can be achieved without undue risk to the patient should be attempted prior to trial enrollment. Decisions about initial resectability will be at the discretion of the local neurosurgeon. In rare instances, the feasibility of completely resecting residual tumor may change as a result of induction chemotherapy; in these cases a second-look operation is encouraged if and may be performed prior to consolidation therapy.

Intervention type: PROCEDURE
Group type: EXPERIMENTAL
Intervention: Surgical resection
Description: For patients with localized AT/RT, gross total resection results in a significant survival benefit. Maximal resection that can be achieved without undue risk to the patient should be attempted prior to trial enrollment. Decisions about initial resectability will be at the discretion of the local neurosurgeon. In rare instances, the feasibility of completely resecting residual tumor may change as a result of induction chemotherapy; in these cases a second-look operation is encouraged if and may be performed prior to consolidation therapy.

Intervention type: PROCEDURE
Group type: EXPERIMENTAL
Intervention: Surgical resection
Description: For patients with localized AT/RT, gross total resection results in a significant survival benefit. Maximal resection that can be achieved without undue risk to the patient should be attempted prior to trial enrollment. Decisions about initial resectability will be at the discretion of the local neurosurgeon. In rare instances, the feasibility of completely resecting residual tumor may change as a result of induction chemotherapy; in these cases a second-look operation is encouraged if and may be performed prior to consolidation therapy.

Intervention type: RADIATION
Group type: EXPERIMENTAL
Intervention: Radiation therapy
Description: The guidelines for this protocol were developed to maximize the curative potential of radiation therapy and minimize the risk of treatment complications for children with newly diagnosed CNS AT/RT. Focal irradiation is indicated for children \< 36 months with no evidence of metastatic disease. Craniospinal irradiation is indicated for children age \> 36 months.