RVU120 With Everolimus for Children With Returned or Worsening Medulloblastoma

Trial details

Who runs it

Bożenna Dembowska Bagińska

Trial code

NCT07865130

Record updated

8 October 2026

Original description

This study will determine the safety and tolerability of RVU120 as a single agent and in combination with the mTOR inhibitor everolimus in children with recurrent or progressive G3 or G4 medulloblastoma and provide preliminary data regarding the efficacy of this treatment approach.Read full original descriptionShow less

Phase I Study of CDK8 Inhibitor RVU120 in Combination With Everolimus in Children With Recurrent or Progressive Group 3 or 4 Medulloblastoma

This study will determine the safety and tolerability of RVU120 as a single agent and in combination with the mTOR inhibitor everolimus in children with recurrent or progressive G3 or G4 medulloblastoma and provide preliminary data regarding the efficacy of this treatment approach.

Inclusion: 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: 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; Recent major surgery - Major surgery including tumor biopsy <14 days before enrollment. Minor neurosurgical procedures (VP shunt, cyst fenestration, central line placement) allowed; 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; Malabsorption - Conditions requiring supplementation or significant bowel/stomach resection preventing adequate RVU120 absorption; Pregnancy/lactation - Pregnant or lactating patients. Negative serum pregnancy test required for patients of childbearing potential; 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.

ClinicalTrials.gov NCT07865130