Medulloblastoma RecurrentPhase 1MEDWAYNCT07865130
Study of CDK8 Inhibitor RVU120 in Combination With Everolimus in Children With Recurrent or Progressive Group 3 or 4 Medulloblastoma
A Phase 1 study testing RVU120 and Everolimus (Afinitor) tablets in people with Medulloblastoma Recurrent and Medulloblastoma, run by Bożenna Dembowska Bagińska at 1 site in Poland.
Trial summary
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 more about this study
- Who is it for?
- Ages 3 to 18 years
- Conditions the study is for
- Medulloblastoma Recurrent, Medulloblastoma
- What is being tested?
- RVU120 and Everolimus (Afinitor) tablets
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 sitePoland
- Study dates
- Sep 2026to Jun 2033
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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)
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- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Poland1 site
Instytut "Pomnik - Centrum Zdrowia Dziecka", Centrum Wsparcia Pediatrycznych Badań Klinicznych
Warsaw, Masovian Voivodeship, 04-730
Magdalena Kozłowska, m.kozlowska@ipczd.pl
Bożenna Dembowska-Bagińska
About this study
Official title: 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.
- Conditions
- Medulloblastoma Recurrent, Medulloblastoma
- Being tested
- RVU120, Everolimus (Afinitor) tablets
- Keywords
- recurrent or progressive G3 or G4 medulloblastoma
- Medical subject headings
- Medulloblastoma, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RVU120Drug
Experimantal - RVU120
Everolimus (Afinitor) tabletsDrug
RVU120 + everolimus
| Study group | Role | What they receive |
|---|---|---|
| Monotherapy - RVU120 | Experimental | Monotherapy dose finding arm - patient will be treated with single agent RVU120 with interpatient dose escalation to determine MTD and/or RP2D Receives: Drug: RVU120 |
| Combination therapy: RVU120+everolimus | Experimental | Combination therapy dose finding arm - patient will be treated with RVU120 in combination therapy with everolimus Receives: Drug: RVU120; Drug: Everolimus (Afinitor) tablets |
| Combination therapy: RVU120+everolimus (expansion) | Experimental | Expansion cohort - patient will be treated with RVU120 in combination therapy with everolimus - efficacy cohort Receives: Drug: RVU120; Drug: Everolimus (Afinitor) tablets |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency and nature of AEs, SAEs and DLTs according to CTCAE v5.0 in RVU120 monotherapy and combination therapy with everolimus
Assessment of adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs) occurring during treatment with RVU120 monotherapy and RVU120 combined with everolimus. All events will be collected and graded according to CTCAE v5.0.
Measured: From Day1 to 30 days after last dose
MTD and/or RP2D of RVU120 as a single agent and in combination with everolimus
Determination of the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of RVU120 administered as a single agent and in combination with everolimus in children with recurrent or progressive Group 3 or Group 4 medulloblastoma. MTD will be defined based on the occurrence of dose-limiting toxicities (DLTs) according to CTCAE v5.0 during the predefined DLT evaluation period. RP2D will be established based on MTD, overall safety profile, and clinical tolerability.
Measured: During Cycle 1 (DLT evaluation period; each cycle is 28 days)
Secondary outcomes (9)
Peak Plasma Concentration (Cmax) of RVU120
Cmax determined from serial blood sampling following administration of RVU120 as monotherapy and in combination with everolimus in children with recurrent or progressive Group 3 or Group 4 medulloblastoma, using non-compartmental analysis
Measured: Day 1 and Day 14 of Cycle 1 (each cycle is 28 days); Day 1 of subsequent cycles
Time to Peak Plasma Concentration (Tmax) of RVU120
Tmax determined from serial blood sampling following administration of RVU120 as monotherapy and in combination with everolimus, based on the time to maximum observed plasma concentration using non-compartmental analysis
Measured: Day 1 and Day 14 of Cycle 1; Cycle 4 Day 1; Cycle 7 Day 1; and every 4 cycles thereafter through study completion (up to 2 years).
Area Under the Plasma Concentration-Time Curve (AUC) of RVU120
AUC determined from serial plasma RVU120 concentrations following administration as monotherapy and in combination with everolimus, using non-compartmental analysis
Measured: Day 1 and Day 14 of Cycle 1; Cycle 4 Day 1; Cycle 7 Day 1; and every 4 cycles thereafter through study completion (up to 2 years).
Terminal Elimination Half-Life (t½) of RVU120
t½ estimated from the terminal phase of the plasma concentration-time profile of RVU120 following administration as monotherapy and in combination with everolimus, using non-compartmental analysis
Measured: Day 1 and Day 14 of Cycle 1; Cycle 4 Day 1; Cycle 7 Day 1; and every 4 cycles thereafter through study completion (up to 2 years).
Everolimus Trough Concentration (Ctrough) During Combination Therapy
Everolimus trough concentrations (Ctrough) measured in patients receiving RVU120 in combination with everolimus. Blood samples are collected immediately prior to dosing (pre-dose) at protocol-specified treatment days to assess steady-state trough levels during combination therapy.
Measured: Pre-dose on Cycle 1 Day 1 and Cycle 1 Day 7, and before each subsequent treatment cycle through study completion (up to 2 years).
Overall Response Rate (ORR)
ORR assessed for RVU120 in combination with everolimus in children with recurrent or progressive Group 3 or Group 4 medulloblastoma, following RAPNO guidelines and stratified by molecular subgroup (G3 vs. G4) and MYC/MYCN expression.
Measured: From start of treatment until disease progression or death, assessed up to 24 months (per protocol follow-up schedule)
Duration of Response
Duration of Response for patients achieving an objective response to RVU120 + everolimus, evaluated according to RAPNO guidelines and stratified by molecular subgroup (G3 vs. G4) and MYC/MYCN expression
Measured: From date of first documented response until disease progression or death, assessed up to 24 months.
Progression-Free Survival (PFS)
PFS assessed for RVU120 + everolimus in children with recurrent or progressive Group 3 or Group 4 medulloblastoma, following RAPNO criteria and stratified by molecular subgroup (G3 vs. G4) and MYC/MYCN expression.
Measured: From start of treatment until disease progression or death, whichever occurs first, assessed up to 24 months
Overall Survival (OS)
OS assessed for RVU120 + everolimus in children with recurrent or progressive Group 3 or Group 4 medulloblastoma, stratified by molecular subgroup (G3 vs. G4) and MYC/MYCN expression
Measured: From start of treatment until death from any cause, assessed up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2026
- Study startSep 2026 (estimated)
- Primary completionJun 2033 (estimated)
- Study completionJun 2033 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Medulloblastoma RecurrentStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Bożenna Dembowska Bagińska
- Sponsor type
- University, hospital or other
- Collaborators
- Ryvu Therapeutics SA
- Responsible party
- Sponsor-investigator, Bożenna Dembowska Bagińska, Children's Memorial Health Institute, Poland
- Investigators
- Bożenna Dembowska-Bagińska, Principal investigator, The Children's Memorial Health InstituteAleksander Wiśniewski, Study director, The Children's Memorial Health InstituteMagdalena Kozłowska, Study chair, The Children's Memorial Health Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07865130
- Sponsor's protocol ID
- MEDWAY
- Acronym
- MEDWAY
- Status last verified
- Oct 2026
- First submitted
- 5 Aug 2026
- Last updated
- 8 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided