A Study of a New Way to Treat Children and Young Adults With a Brain Tumor Called NGGCT

Inclusion Criteria:

   - Patients must be >= 3 years and < 30 years at the time of study enrollment

   - Patients must be newly diagnosed with localized primary CNS NGGCT of the suprasellar
   and/or pineal region by pathology and/or serum or cerebrospinal fluid (CSF) elevation
   of AFP above institutional normal or > 10 ng/mL or human chorionic gonadotropin (hCG)
   beta > 100 mIU/mL as confirmed by Rapid Central Marker Screening Review on
   APEC14B1-CNS. Suprasellar, pineal and bifocal tumors are included. (CSF tumor markers
   and cytology must be within 31 days prior to enrollment and start of protocol therapy
   [repeat if necessary]. Serum tumor markers, AFP and hCGbeta must be within 7 days
   prior to enrollment and start of protocol therapy [repeat if necessary]). Basal
   ganglia or other primary sites are excluded

   - Patients with any of the following pathological elements are eligible: endodermal
   sinus (yolk sac), embryonal carcinoma, choriocarcinoma, malignant/immature teratoma
   and mixed germ cell tumor (GCT) (i.e., may include some pure germinoma) if malignant
   elements listed above are present. Patients with only mature teratoma are excluded.
   Patients with pure germinoma admixed with mature teratoma are excluded (would be
   eligible for pure germinoma protocols)

   - Patients must have a cranial MRI with and without gadolinium at diagnosis/prior to
   enrollment. If surgical resection is performed, patients must have pre-operative and
   post operative brain MRI with and without gadolinium. The post operative brain MRI
   should be obtained within 72 hours of surgery. If patient has a biopsy only,
   post-operative brain MRI is recommended but not required (within 31 days prior to
   study enrollment and start of protocol therapy )

   - Patients must have a spine MRI with gadolinium obtained at diagnosis/prior to
   enrollment. Spine MRI with and without gadolinium is recommended (within 31 days prior
   to study enrollment and start of protocol therapy)

   - Lumbar CSF must be obtained prior to study enrollment unless medically
   contraindicated. If a patient undergoes surgery and lumbar CSF cytology cannot be
   obtained at the time of surgery, then it should be performed at least 10 days
   following surgery and prior to study enrollment. False positive cytology can occur
   within 10 days of surgery

   - Patients must have RAPID CENTRAL TUMOR MARKER REVIEW CSF tumor markers obtained prior
   to enrollment unless medically contraindicated. Ventricular CSF obtained at the time
   of CSF diversion procedure (if performed) is acceptable for tumor markers but lumbar
   CSF is preferred. In case CSF diversion and biopsy/surgery are combined, CSF tumor
   markers should be collected first

   - Peripheral absolute neutrophil count (ANC) >= 1000/uL (within 7 days prior to
   enrollment)

   - Platelet count >= 100,000/uL (transfusion independent) (within 7 days prior to
   enrollment)

   - Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions) (within 7 days
   prior to enrollment)

   - Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
   mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows (within 7 days
   prior to enrollment):

      - Age: Maximum serum creatinine (mg/dL)

         - 3 to < 6 years: 0.8 (male), 0.8 (female)

         - 6 to < 10 years: 1 (male), 1 (female)

         - 10 to < 13 years: 1.2 (male), 1.2 (female)

         - 13 to < 16 years: 1.5 (male), 1.4 (female)

         - >= 16 years: male (1.7), 1.4 (female)

   - Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to
   enrollment)

   - Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135
   U/L (within 7 days prior to enrollment)

      - Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the
      value of 45 U/L

   - Central nervous system function defined as:

      - Patients with seizure disorder may be enrolled if on anticonvulsants and well
      controlled

      - Patients must not be in status epilepticus, coma or assisted ventilation prior to
      study enrollment

   - Protocol therapy must begin within 31 calendar days of definitive surgery or clinical
   diagnosis, whichever is later. If a biopsy only was performed, the biopsy date will be
   considered the date of definitive surgery. For patients who have a biopsy or
   incomplete resection at diagnosis followed by additional surgery, the date of the last
   resection will be considered the date of definitive surgery.

   - All patients and/or their parents or legal guardians must sign a written informed
   consent

   - All institutional, Food and Drug Administration (FDA), and National Cancer Institute
   (NCI) requirements for human studies must be met

   - NEUROCOGNITIVE FUNCTION AND QUALITY OF LIFE ASSESSMENT:

   - English-, Spanish-, or French- speaking

      - Note: Patients who speak a language other than English, Spanish, or French will
      be allowed to participate in ACNS2021 but will not complete the neurocognitive
      and quality of life assessments

   - No known history of neurodevelopmental disorder prior to diagnosis of NGGCT (e.g.,
   Down syndrome, fragile X, William syndrome, intellectual disability). Patients with
   NF1 will be allowed to participate

   - Additional eligibility criteria for the COG Standardized Neuropsychological Battery
   only: must be at a site that has a psychologist to administer the battery

      - Note: If not eligible for the COG Standardized Battery, patients should still
      complete the Behavior Rating Inventory of Executive Function, Second Edition
      (BRIEF-2), Pediatric Quality of Life Inventory (PedsQL), Adaptive Behavior
      Assessment System Third Edition (ABAS-3), and Behavior Assessment System for
      Children, Third Edition (BASC-3) questionnaires

Exclusion Criteria:

   - Patients with tumors located outside the ventricles (i.e., basal ganglia, thalamus)

   - Patients with only mature teratoma and non-elevated markers upon tumor sampling at
   diagnosis

   - Patients who have received any prior tumor-directed therapy for their diagnosis of
   NGGCT other than surgical intervention and corticosteroids

   - Patients with metastatic disease (i.e., MRI evaluation, lumbar CSF cytology or
   intraoperative evidence of dissemination)

   - Female patients who are pregnant, since fetal toxicities and teratogenic effects have
   been noted for several of the study drugs

      - Note: Serum and urine pregnancy tests may be falsely positive due to
      HCGbeta-secreting germ cell tumors. Ensure the patient is not pregnant by
      institutional standards

   - Lactating females who plan to breastfeed their infants

   - Sexually active patients of reproductive potential who have not agreed to use an
   effective contraceptive method for the duration of their study participation