Embryonal Tumor With Multilayered Rosettes

Inclusion criteria

• Participants must have either a molecularly or histologically confirmed embryonal tumor with multilayered rosettes.
• For enrollment, a confirmation of a minimum of 10-20 unstained formalin-fixed paraffin-embedded (FFPE) slides or 1 block (15-20 mg) with tumor content of 40% or greater is required. Anything less must be discussed and approved by the study chairs prior to enrollment.
• Prior Therapy:
• Cohort 1 participants must not have received any prior tumor-directed therapy other than surgical resection.
• Cohort 2 and 3 participants may receive tumor-directed therapy prior to enrollment. These participants must be discussed with study chairs prior to enrollment.
• Participants must not have received prior radiation for treatment of tumor.
• Participants of any age are eligible.
• Participants should begin induction chemotherapy within 28 days of the most recent definitive surgical procedure. Participants beginning therapy beyond 28 days from surgery, will need to discuss with study chairs.
• Cohort specific eligibility
• Cohort 1: Gross-total resection, Eligible for early radiotherapy (please see age criteria below), and no evidence of metastatic disease.
• Cohort 2: Gross-total resection, high dose chemotherapy (please see age criteria below), and no evidence of metastatic disease.
• Cohort 3A: Metastatic or residual disease, and early radiotherapy.
• Cohort 3B: Metastatic or residual disease, and high dose chemotherapy.
• Radiotherapy Age Criteria (at the time of planned radiation): \>12 months of age for participants with infratentorial tumor OR \>15 months of age for participants with supratentorial tumor. For participants being treated on radiotherapy-containing arms, the legal parent/guardian or patient and the physician must be willing to allow the use of radiotherapy for treatment.
• Performance Score: Karnofsky \>= 50 for participants \> 16 years of age and Lansky \>= 50 for participants \<=16 years of age. Participants 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.
• Organ Function Requirements:
• Peripheral absolute neutrophil count (ANC) \> 75,000/mm3
• Platelet count \> 75,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 72 hours prior to enrollment).
• Adequate Renal Function defined as: a. Serum creatinine \< 1.5 x upper limit normal (ULN) based on age and gender.
• Adequate Liver Function defined as:
• Total bilirubin \< 1.5 x upper limit of normal (ULN) for age; in presence of Gilbert's syndrome, total bilirubin \< 3 x ULN or direct bilirubin \< 1.5 x ULN,
• alanine aminotransferase (ALT) \< 3 x ULN,
• aspartate aminotransferase (AST) \< 3 x ULN,
• Adequate Neurologic Function defined as: a. Participants with seizure disorder may be enrolled if well controlled. Participants on enzyme inducing anticonvulsants may be excluded pending interaction(s) with study drugs.
• As chemotherapeutic agents used in this trial are known to be teratogenic, women and men of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and 4 months after completion of study therapy. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
• Participants must be enrolled on PNOC COMP prior to enrollment on PNOC031 if PNOC COMP is open to accrual at the enrolling institution.
• A legal parent/guardian or patient must be able to understand, and willing to sign, a written informed consent and assent document, as appropriate.

Exclusion criteria

• Cohort 1 only: Participants who have received any prior tumor-directed therapy other than surgical intervention
• Participants who are receiving any other tumor directed investigational agents.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to the agents used in study.
• Uncontrolled intercurrent illness.
• Women of childbearing potential must not be pregnant or breast-feeding.