Inclusion Criteria:
* Diagnosis: Recurrent/progressive Group 3 or Group 4 medulloblastoma confirmed by CLIA-certified methylation testing. Patients ≥4 years at initial diagnosis must have received CSI + systemic chemotherapy; patients \<4 years must have received systemic chemotherapy (CSI not required).
* Age: 3 to ≤18 years.
* Ability to swallow capsules/tablets required.
* BSA: 0.4-2.5 m².
* Disease status: Metastatic disease allowed. Phase 1 cohorts: measurable disease not required; patients post-GTR ± reirradiation, isolated LM disease, or positive CSF cytology eligible. Patients post-reirradiation may enroll after required washout. Expansion cohort: measurable disease per RAPNO required.
* Prior therapy: Recovery from acute toxicities to ≤CTCAE v5.0 Grade 1. Required washouts: - Myelosuppressive chemo ≥21 days (≥42 days for nitrosoureas) - Biologic agents ≥7 days (long-lasting AEs: extended) - Monoclonal antibodies ≥28 days - Radiation: CSI/TBI/≥50% pelvis ≥42 days; focal RT ≥14 days - Autologous transplant ≥6 months - Growth factors ≥7 days (PEG ≥14 days)
* Organ function: Adequate marrow, liver, and renal function per protocol thresholds. Neurologic status: Stable deficits ≥1 week; seizures controlled; no enzyme-inducing anticonvulsants.
* Performance: KPS/LPS ≥60. Wheelchair-mobile patients considered ambulatory.
* Pregnancy prevention: Effective contraception required.
* Consent: Ability to understand and sign informed consent/assent.
Exclusion Criteria:
* Pregnancy/lactation - Pregnant or lactating patients. Negative serum pregnancy test required for patients of childbearing potential.
* Clinically significant illness - Serious uncontrolled infections or significant cardiac, pulmonary, hepatic, or other organ dysfunction that may increase risk or interfere with study procedures. Includes prior/concurrent malignancies that may affect safety or efficacy assessment.
* Concurrent therapy: any anticancer or investigational therapy; corticosteroids allowed only if stable or decreasing ≥7 days; strong CYP1A2/CYP3A4/3A5 inducers/inhibitors or P-gp inhibitors; prohibited fruits (grapefruit, Seville oranges, starfruit). Must be discontinued ≥7 days or ≥5 half-lives; hypersensitivity to RVU120, everolimus, or rapamycin derivatives; live virus vaccine \<21 days before enrollment (everolimus); hereditary galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption.
* Recent major surgery - Major surgery including tumor biopsy \<14 days before enrollment. Minor neurosurgical procedures (VP shunt, cyst fenestration, central line placement) allowed.
* Malabsorption - Conditions requiring supplementation or significant bowel/stomach resection preventing adequate RVU120 absorption.
* Prior CDK8 or mTOR inhibitors - Prior therapy with CDK8 inhibitors or mTOR inhibitors (everolimus, sirolimus, temsirolimus).
* Inability to comply - Patients unable or unwilling to adhere to study visits, assessments, drug administration, or required restrictions.
