Phase I study of CDK8 inhibitor RVU120 in combination with everolimus in children with recurrent or progressive Group 3 or 4 medulloblastoma; MEDWAY

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Instytut Pomnik Centrum Zdrowia Dziecka

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Diseases [C] - Nervous System Diseases [C10]

Decision date (initial)

2026-04-23

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

100 % Agencja Badań Medycznych

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Pharmacokinetic, Safety, Efficacy

1. To evaluate the safety and toxicity of RVU120 as a single agent and combined with everolimus when administered to children with recurrent or progressive G3 or G4 medulloblastoma
2. To determine the MTD and/or RP2D of RVU120 as a single agent and in combination with everolimus in children with recurrent or progressive G3 or G4 medulloblastoma.

Secondary objectives 1

1. 1. To determine the plasma pharmacokinetics (PK) of RVU120 as a single agent and in combination with everolimus in children with recurrent or progressive G3 or G4 medulloblastoma 2. To measure everolimus trough levels when given in combination with RVU120 at all tested dose levels 3. To make a preliminary assessment of the efficacy of combination therapy in children with recurrent or progressive G3 or G4 medulloblastoma with overall response rate (ORR), duration of response, progression-free survival (PFS), and overall survival (OS) stratified by molecular subgroup (G3 vs. G4) and MYC or MYCN expression

Conditions and MedDRA coding

Medulloblastoma (recurrent or progressive)

Study design 5 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. Inclusion criteria 1.) Diagnosis: G3 or G4 medulloblastoma that is recurrent or progressive following up-front standard of care therapy. Subgroup must be determined either at diagnosis or recurrence via CLIA-certified methylation testing. 2.) Age (at time of study enrollment): 3 years to ≤18 years 3.) Patients must be able to swallow capsules and/or tablets 4.) BSA: 0.4-2.5 m2 5.) Disease status: Patients with metastatic disease are eligible for both cohorts of the study. a. Dose-finding cohorts b. Efficacy expansion cohort 6.) Prior therapy - Patients must have recovered from the acute treatment related toxicities (defined as ≤ CTCAE v5.0 grade 1 unless otherwise defined in inclusion criteria #7) of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study 7.) Organ function - Patients must have adequate organ and marrow function 8.) Neurologic status 9.) Performance level - Karnofsky Performance Scale (for > 16 years of age) or Lansky Performance Score (for ≤ 16 years of age) 10.) Pregnancy prevention - Patients of childbearing or child fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study. 11.) Informed consent - The patient or parent/guardian is able to understand the consent and is willing to sign a written informed consent document according to institutional guidelines

Exclusion criteria 1

1. Exclusion criteria 1.) Pregnancy and lactation status: Pregnant or lactating patients are excluded from this study. Patients of childbearing potential must have a negative serum pregnancy test prior to study enrollment. 2.) Concurrent illness: Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic, or other organ dysfunction), that in the opinion of the investigator would compromise the patient’s ability to tolerate protocol therapy, put them at additional risk for toxicity or would interfere with the study procedures or results. 3.) Concurrent therapy 4.) Recent major surgery: patients that have undergone major surgery including tumor biopsy within 14 days of enrollment. 5.) Malabsorption that requires supplementation or significant bowel or stomach resection that would preclude adequate absorption of RVU120. 6.) Previous therapy with a CDK8 inhibitor or an mTOR inhibitor (such as everolimus, sirolimus, or temsirolimus). 7.) Inability to participate: Patients who in the opinion of the investigator are unwilling or unable to return for required follow-up visits or obtain follow-up studies required to assess toxicity to therapy or to adhere to drug administration plan, other study procedures, and study restrictions.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1. Frequency and nature of AEs, SAEs and DLTs according to CTCAE v5.0 in RVU120 monotherapy and combination therapy with everolimus 2. MTD and/or RP2D of RVU120 as a single agent and in combination with everolimus

Secondary endpoints 1

1. 1. PK parameters of RVU120 as a single agent and in combination with everolimus, including Cmax, AUCτ, tmax, AUC0 - ∞, t1/2 2. Ctrough of everolimus in combination with RVU120 3. Overall response rate (ORR), duration of response, progression-free survival (PFS), and overall survival (OS) in accordance with RAPNO guidelines, where applicable, stratified by molecular subgroup (G3 vs. G4) and MYC or MYCN expression in combination therapy of RVU120 and everolimus

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Instytut Pomnik Centrum Zdrowia Dziecka

Sponsor organisation

Instytut Pomnik Centrum Zdrowia Dziecka

Address

Aleja Dzieci Polskich 20

City

Warsaw

Postcode

04-730

Country

Poland

Scientific contact point

Organisation

Instytut Pomnik Centrum Zdrowia Dziecka

Contact name

prof. dr hab. n. med. Bożenna Dembowska-Bagińska

Public contact point

Organisation

Instytut Pomnik Centrum Zdrowia Dziecka

Contact name

Mariola Modzelewska

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 16 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications