Ribociclib and Everolimus in Treating Children With Recurrent or Refractory Malignant Brain Tumors

Inclusion Criteria

• ELIGIBILITY FOR SCREENING
• Patients with a histologically confirmed diagnosis of high-grade glioma (HGG), medulloblastoma, CNS embryonal tumor (not otherwise specified [NOS]), ependymoma, or atypical teratoid rhabdoid tumor (ATRT) that is recurrent, progressive or refractory
• Patients with recurrent diffuse intrinsic pontine glioma (DIPG) with typical radiographic appearance who have undergone biopsy are eligible provided there is histologic confirmation of malignant glioma World Health Organization (WHO) II-IV; Rb1 screening for these patients is required only if adequate tissue is available
• Patients with recurrent brainstem tumors with an atypical presentation who have undergone biopsy are eligible provided there is histologic confirmation of malignant glioma WHO II-IV; these patients must undergo Rb1 screening; these patients must have radiographic evidence of progression
• Patients with secondary malignant gliomas will be eligible for this study but should conform to all other eligibility requirements; patients with low-grade gliomas are excluded
• Formalin fixed paraffin embedded tumor tissue (preferably from the most recent recurrence) must be available to assess Rb1 protein status prior to enrollment on phase I or surgical study; if the subject has results from prior Rb1 IHC testing in a Clinical Laboratory Improvement Act (CLIA)-certified laboratory the requirement for screening to assess Rb1 protein status is waived
• Patients with recurrent diffuse intrinsic brain stem glioma (DIPG) that has an atypical presentation must also submit the tumor tissue for Rb1 protein status confirmation or provide previous testing results from a CLIA certified laboratory; patients who have been biopsied for atypical DIPG but do not have sufficient tissue for Rb1 screening are not eligible
• Body surface area (BSA)
• Patients enrolled on dose level -1 must have BSA >= 0.55m^2
• Patients enrolled on dose level -0.5 must have BSA >= 0.75m^2
• Patients enrolled on dose level 0 must have BSA >= 0.55m^2
• Patients enrolled on dose level 1 must have BSA >= 0.75m^2
• Patients enrolled on dose level 2 and 3 must have BSA >= 0.45m^2
• Patients who are candidates for enrollment for the phase I or surgical studies must sign a screening consent and provide pre-trial tumor material for Rb1 testing unless testing is not needed due to diagnosis or the availability of prior Rb1 IHC results; the screening consent is to be obtained according to institutional guidelines
• Patients screened for this trial should be expected to meet the criteria for treatment
• PRIOR TO STUDY ENROLLMENT
• PHASE I (STRATUM 1): Patient has intact Rb1 protein confirmed either from previous results or screened tissue; all testing must be performed in a CLIA certified laboratory; DIPG patients with radiographically typical appearance will be waived from this requirement
• PHASE I (STRATUM 1): Patients with a histologically confirmed diagnosis of a primary CNS tumor that is recurrent, progressive, or refractory; all tumors must have histologic verification of HGG, medulloblastoma, CNS embryonal tumor (NOS), ependymoma, or ATRT; patients with low-grade gliomas are excluded
• PHASE I (STRATUM 1): Patients with progressive DIPG, as defined by progressive neurologic abnormalities or worsening neurologic status not explained by causes unrelated to tumor progression (e.g., anticonvulsant or corticosteroid toxicity wean, electrolyte disturbances, sepsis, hyperglycemia, etc.), OR an increase in the bi-dimensional measurement, taking as a reference the smallest disease measurement recorded since last treatment, OR the appearance of a new tumor lesion since diagnosis
• Please note:
• Patients with a radiographically typical DIPG, defined as a tumor with a pontine epicenter and diffuse involvement of more than 2/3 of the pons, are eligible without histologic confirmation
• Patients with pontine lesions that do not meet these radiographic criteria will be eligib