Embryonal Tumor With Multilayered Rosettes

The eligibility criteria listed below are interpreted literally and cannot be waived.

Inclusion Criteria:

1. Participants must have either a molecularly or histologically confirmed embryonal tumor with multilayered rosettes.

2. 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.

3. Prior Therapy:

4. Cohort 1 participants must not have received any prior tumor-directed therapy other than surgical resection.

5. Cohort 2 and 3 participants may receive tumor-directed therapy prior to enrollment. These participants must be discussed with study chairs prior to enrollment.

6. Participants must not have received prior radiation for treatment of tumor.

7. Participants of any age are eligible.

8. 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.

9. Cohort specific eligibility

10. Cohort 1: Gross-total resection, Eligible for early radiotherapy (please see age criteria below), and no evidence of metastatic disease.

11. Cohort 2: Gross-total resection, high dose chemotherapy (please see age criteria below), and no evidence of metastatic disease.

12. Cohort 3A: Metastatic or residual disease, and early radiotherapy.

13. Cohort 3B: Metastatic or residual disease, and high dose chemotherapy.

14. 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.

15. 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.

16. Organ Function Requirements:

17. Peripheral absolute neutrophil count (ANC) > 75,000/mm3

18. Platelet count > 75,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 72 hours prior to enrollment).

19. Adequate Renal Function defined as:

a. Serum creatinine < 1.5 x upper limit normal (ULN) based on age and gender.

11. Adequate Liver Function defined as:

12. 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,

13. alanine aminotransferase (ALT) < 3 x ULN,

14. aspartate aminotransferase (AST) < 3 x ULN,

15. 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.

13. 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.

14. Participants must be enrolled on PNOC COMP prior to enrollment on PNOC031 if PNOC COMP is open to accrual at the enrolling institution.

15. 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

1. Cohort 1 only: Participants who have received any prior tumor-directed therapy other than surgical intervention

2. Participants who are receiving any other tumor directed investigational agents.

3. History of allergic reactions attributed to compounds of similar chemical or biologic composition to the agents used in study.

4. Uncontrolled intercurrent illness.

5. Women of childbearing potential must not be pregnant or breast-feeding.