Pilot Study of IT Topotecan and Maintenance Chemotherapy for HR-EBTs in Children < 6 Years, Post Consolidation

Inclusion Criteria:

1. Tumor Tissue Sample
2. Age: Patient must be aged ≥ 0 years to ≤ 6 years at the time of definitive confirmation of histologic diagnosis of eligible CNS tumor.
3. Diagnoses. Participants must have Central nervous system (CNS) HR-EBT including atypical teratoid rhabdoid tumour (ATRT), group 3 and group 4 medulloblastoma (MB), pineoblastoma, CNS neuroblastoma, embryonal tumor with multi-layered rosettes (ETMR including embryonal tumor with abundant neuropil and true rosettes (ETANTR), ependymoblastoma and ETMR not otherwise specified), medulloepithelioma, CNS embryonal tumor with rhabdoid features (INI-1 intact) and CNS embryonal tumor, not otherwise specified. Metastatic disease included. Any extent of resection included.
4. Cranial and Spine MRI. A baseline MRI brain and spine with and without contrast is required for all patients. cranial MRI (with and without gadolinium) must be done pre-operatively. Post-operatively, cranial MRI (with and without gadolinium) must be done.
5. Lumbar Puncture (LP) CSF for cytopathology (strongly recommended but not mandatory; if medically feasible). A baseline LP CSF cytology either pre-operatively or post-operatively at least 10 days after definitive surgery for all patients if medically feasible (This is not mandatory and will not make the patient ineligible).
6. Life expectancy: Patients must have a life expectancy of greater than 8 weeks from diagnosis.
7. Performance level: Patients must have a performance status corresponding of a Lansky score ≥ 50.
8. Organ Function Requirements: Participants must have normal organ and marrow function as defined below:

Adequate renal function defined as:

\- Creatinine clearance (12-24-hour urine collection) or radioisotope glomerular filtration rate (GFR) ≥ 60 ml/min/1.73m2

Adequate cardiac function defined as:

* Shortening fraction of ≥ 27% by echocardiogram, or
* Ejection fraction of ≥ 47% by radionuclide angiogram.

Adequate pulmonary function defined as:

\- No evidence of dyspnea at rest and a pulse oximetry \> 94% on room air.

Adequate Bone Marrow Function defined as:

* Peripheral absolute neutrophil count (ANC) \> 1000/μL
* Platelet Count \> 100,000/μL (without transfusion for 3 days)
* Hemoglobin greater than 8 gm/dL (may have received red blood cell (RBC) transfusions)

Adequate liver function defined as:

* Total bilirubin ≤ 1.5X upper limit of normal (ULN) within normal institutional limits for age (patients with documented Gilbert's Disease may be enrolled with Study Chair approval and total bilirubin ≤ 2.0 × ULN)
* Alanine Aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 100 U/L

Exclusion criteria:

1. Patients who are receiving any other conventional anti-cancer agents or investigational agents.
2. Patients who received previous therapy including radiotherapy or chemotherapy other than corticosteroids.
3. Presence of another malignancy, except if the other primary malignancy is neither currently clinically significant nor requiring active intervention.
4. Concomitant medications restrictions: Concurrent use of enzyme inducing anticonvulsants (e.g. phenytoin, phenobarbital, and carbamazepine), selected strong inhibitors of cytochrome P450 3A4 include azole antifungals, such as fluconazole, voriconazole, itraconazole, ketoconazole, and strong inducers include drugs such as rifampin, phenytoin, phenobarbitol, carbamazepine, and St. John's wort or CYP450 3A4 stimulators or inhibitors.
5. Other uncontrollable medical disease: Patient has a severe and uncontrollable medical disease (i.e., uncontrolled diabetes, hyperglycemia, chronic renal disease or active uncontrolled infection), has chronic liver disease (i.e., chronic active hepatitis and cirrhosis), hypercholesterolemia (serum cholesterol \>300 mg/dL), intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, active hyperparathyroidism, or psychiatric illness/social situations that would limit compliance with study requirements.
6. Patients who have a known diagnosis of human immunodeficiency virus (HIV) infection, hepatitis B or C.
7. Ineligible diagnoses for study entry by neuropathology: This includes sonic hedgehog (SHH) and wingless (WNT) MBs, all ependymomas, all choroid plexus carcinomas, all high grade glial and glio-neuronal tumors, all diffuse midline gliomas, all primary CNS germ cell tumors, all primary CNS sarcomas, all primary or metastatic CNS lymphomas and solid leukemic lesions (chloromas, granulocytic sarcomas).
8. The participant or parent(s)/guardian(s) cannot comply with the study visit schedule and other protocol requirements, in the investigator's opinion.

All patients must meet inclusion/exclusion criteria prior to starting any protocol therapy.