A Pilot Study of Intrathecal Topotecan and Maintenance Chemotherapy in the Post-consolidation Setting for the Treatment of High-risk Embryonal Central Nervous System Tumours in Children Less Than 6 Years of Age
Pilot study to determine feasibility of adding intrathecal chemotherapy and maintenance therapy after high dose chemotherapy for treatment of newly diagnosed HR-EBTs in patients less than 6 years of age.
⁃ Tumor Tissue Sample
⁃ Age: Patient must be aged ≥ 0 years to ≤ 6 years at the time of definitive confirmation of histologic diagnosis of eligible CNS tumor.
⁃ 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.
⁃ 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.
⁃ 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).
⁃ Life expectancy: Patients must have a life expectancy of greater than 8 weeks from diagnosis.
⁃ Performance level: Patients must have a performance status corresponding of a Lansky score ≥ 50.
⁃ 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