[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100659571":3},{"organization":4,"outcomesModule":7,"designInfo":111,"detailedDescription":114,"studyPopulation":114,"armGroups":118,"interventions":134,"overallOfficials":144,"centralContacts":155,"locations":165,"responsibleParty":182,"collaborators":186,"id":190,"slug":191,"hasResults":192,"nctId":193,"briefTitle":194,"officialTitle":195,"acronym":196,"eligibilityCriteria":197,"healthyVolunteers":192,"sex":198,"minAge":199,"maxAge":200,"enrollmentInfo":201,"targetDuration":114,"studyType":204,"phases":205,"briefSummary":207,"conditions":208,"keywords":211,"overallStatus":213,"whyStopped":114,"lastUpdateSubmitDate":214,"lastUpdatePostDateStruct":215,"startDateStruct":218,"completionDateStruct":220,"leadSponsor":222,"locationsCount":223},{"fullName":5,"class":6},"Children's Memorial Health Institute, Poland","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":17,"otherOutcomes":52},[9,13],{"measure":10,"description":11,"timeFrame":12},"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.","From Day1 to 30 days after last dose",{"measure":14,"description":15,"timeFrame":16},"MTD and\u002For RP2D of RVU120 as a single agent and in combination with everolimus","Determination of the maximum tolerated dose (MTD) and\u002For 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.","During Cycle 1 (DLT evaluation period; each cycle is 28 days)",[18,22,26,29,32,36,40,44,48],{"measure":19,"description":20,"timeFrame":21},"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","Day 1 and Day 14 of Cycle 1 (each cycle is 28 days); Day 1 of subsequent cycles",{"measure":23,"description":24,"timeFrame":25},"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","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).",{"measure":27,"description":28,"timeFrame":25},"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",{"measure":30,"description":31,"timeFrame":25},"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",{"measure":33,"description":34,"timeFrame":35},"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.","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).",{"measure":37,"description":38,"timeFrame":39},"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\u002FMYCN expression.","From start of treatment until disease progression or death, assessed up to 24 months (per protocol follow-up schedule)",{"measure":41,"description":42,"timeFrame":43},"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\u002FMYCN expression","From date of first documented response until disease progression or death, assessed up to 24 months.",{"measure":45,"description":46,"timeFrame":47},"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\u002FMYCN expression.","From start of treatment until disease progression or death, whichever occurs first, assessed up to 24 months",{"measure":49,"description":50,"timeFrame":51},"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\u002FMYCN expression","From start of treatment until death from any cause, assessed up to 24 months",[53,57,61,64,68,72,75,78,82,85,88,92,96,100,104,108],{"measure":54,"description":55,"timeFrame":56},"Change in Tumor Pharmacodynamic (PD) Markers (IHC)","Change in CDK8- and mTOR-dependent phosphorylation events (e.g., pSTAT5, p4EBP-1) measured by immunohistochemistry (IHC) in post-treatment versus pre-study tumor samples in patients treated with RVU120 monotherapy or RVU120 + everolimus.\n\nUnit of Measure: H-score or % positive tumor cells","Baseline (Screening) and Cycle 4 Day 1 (each cycle is 28 days)",{"measure":58,"description":59,"timeFrame":60},"Transcriptomic Changes in Tumor Tissue (RNAseq)","Transcriptomic changes between pre-treatment and post-treatment tumor samples assessed by RNA sequencing (RNAseq) in patients receiving RVU120 monotherapy or RVU120 + everolimus.\n\nUnit of Measure: Fold-change in gene expression (log2FC)","Baseline tumor sample (Screening) and post-treatment tumor biopsy at protocol-specified on-treatment time point (e.g., Cycle 4 Day 1).",{"measure":62,"description":63,"timeFrame":60},"CDK8- and mTOR-Dependent Phosphorylation Events (IHC)","Levels of CDK8- and mTOR-dependent phosphorylation events (e.g., pSTAT5, p4EBP-1) measured by IHC in tumor samples from patients treated with RVU120 ± everolimus.\n\nUnit of Measure: H-score or % positive tumor cells",{"measure":65,"description":66,"timeFrame":67},"Correlation Between PD Marker Changes and Clinical Response","Correlation between changes in PD markers (IHC and RNAseq) and clinical response to RVU120 ± everolimus using correlation coefficients (e.g., Spearman's rho).Unit of Measure: Correlation coefficient (Spearman's rho)","Cycle 4 Day 1 (each cycle is 28 days) and clinical response assessed up to 24 months",{"measure":69,"description":70,"timeFrame":71},"CDK8 Expression in Tumor Tissue (IHC)","CDK8 expression assessed by immunohistochemistry (IHC) in pre-treatment tumor samples.\n\nUnit of Measure: H-score or % positive tumor cells","Pre-treatment tumor assessments (Screening).",{"measure":73,"description":74,"timeFrame":71},"MYC and MYCN Copy Number Variations (FISH\u002FMLPA)","MYC and MYCN copy number variations assessed by FISH or MLPA in pre-treatment tumor samples.\n\nUnit of Measure: Copy number category (e.g., amplified \u002F non-amplified)\n\n* MYC and MYCN copy number variations by FISH\n* Transcriptomic profiles by RNAseq\n* Additional diagnostic or molecular biomarkers Associations will be evaluated relative to treatment response.",{"measure":76,"description":77,"timeFrame":71},"Baseline Tumor Transcriptomic Profiles (RNAseq)","Transcriptomic profiles assessed by RNA sequencing (RNAseq) in pre-treatment tumor samples.\n\nUnit of Measure: Gene expression profile (normalized counts)\n\n* MYC and MYCN copy number variations by FISH\n* Transcriptomic profiles by RNAseq\n* Additional diagnostic or molecular biomarkers Associations will be evaluated relative to treatment response.",{"measure":79,"description":80,"timeFrame":81},"Correlation Between Baseline Biomarkers and Treatment Response","Correlation between baseline tumor biomarkers (CDK8 expression, MYC\u002FMYCN copy number, transcriptomic profiles) and treatment response to RVU120 ± everolimus using correlation coefficients (e.g., Spearman's rho).\n\nUnit of Measure: Correlation coefficient (Spearman's rho)\n\n* MYC and MYCN copy number variations by FISH\n* Transcriptomic profiles by RNAseq\n* Additional diagnostic or molecular biomarkers Associations will be evaluated relative to treatment response.","Baseline (Screening) and clinical response assessed up to 24 months",{"measure":83,"description":84,"timeFrame":56},"Change in Cell-Free Medulloblastoma DNA Levels (NGS)","Change in cell-free medulloblastoma DNA (cfDNA) levels in cerebrospinal fluid (CSF) and plasma between pre-treatment and post-treatment samples, assessed using next-generation sequencing (NGS), in patients receiving RVU120 monotherapy or RVU120 in combination with everolimus.\n\nUnit of Measure: cfDNA concentration (copies\u002FmL or NGS-derived equivalent)",{"measure":86,"description":87,"timeFrame":56},"Correlation Between Changes in Cell-Free Medulloblastoma DNA and Clinical Response, PK, and PD","Correlation between changes in cell-free medulloblastoma DNA (NGS) and clinical response, pharmacokinetics (PK), and pharmacodynamic (PD) markers in patients treated with RVU120 ± everolimus, assessed using correlation coefficients (e.g., Spearman's rho).\n\nUnit of Measure: Correlation coefficient (Spearman's rho)",{"measure":89,"description":90,"timeFrame":91},"Correlation Between RVU120 Exposure and Clinical Response","Correlation between RVU120 plasma exposure (AUC, Cmax) and clinical response outcomes (e.g., ORR, DoR, PFS, OS) in patients treated with RVU120 monotherapy or RVU120 + everolimus, assessed using correlation coefficients (e.g., Spearman's rho).\n\nUnit of Measure: Correlation coefficient (Spearman's rho)","Cycle 1 PK sampling (Day 1 and Day 14; each cycle is 28 days) and clinical response assessed up to 24 months",{"measure":93,"description":94,"timeFrame":95},"Correlation Between RVU120 Exposure and PD Markers","Correlation between RVU120 plasma exposure (AUC, Cmax) and pharmacodynamic markers (e.g., CDK8- and mTOR-dependent phosphorylation events by IHC; transcriptomic changes by RNAseq).\n\nUnit of Measure: Correlation coefficient (Spearman's rho)","PK and PD data collected throughout study treatment and assessed through study completion (up to 2 years).",{"measure":97,"description":98,"timeFrame":99},"Correlation Between Target Engagement and Clinical Activity","Correlation between target engagement markers (e.g., phosphorylation of pSTAT5, p4EBP-1 by IHC) and clinical activity (e.g., ORR, DoR, PFS, OS) in patients treated with RVU120 ± everolimus.\n\nUnit of Measure: Correlation coefficient (Spearman's rho)","Clinical activity and pharmacodynamic data collected throughout study treatment and assessed through study completion (up to 2 years).",{"measure":101,"description":102,"timeFrame":103},"Correlation Between PK Parameters and PD Markers","Correlation between PK parameters (AUC, Cmax, Tmax) and PD markers (IHC and RNAseq) in patients receiving RVU120 ± everolimus.","PK, PD, and clinical activity data collected throughout study treatment and assessed through study completion (up to 2 years).",{"measure":105,"description":106,"timeFrame":107},"Number of Tumor Tissue Samples Collected (FFPE or Fresh-Frozen)","Number of tumor tissue samples (formalin-fixed paraffin-embedded \\[FFPE\\] or fresh-frozen) collected from participants for future exploratory research.\n\nUnit of Measure: Number of samples","At Screening and Cycle 4 Day 1 (each cycle is 28 days)",{"measure":109,"description":110,"timeFrame":107},"Number of Plasma Samples Collected","Number of plasma samples collected and stored for future exploratory research related to medulloblastoma biology and potential therapeutic approaches.\n\nUnit of Measure: Number of samples",{"allocation":112,"interventionModel":113,"interventionModelDescription":114,"primaryPurpose":115,"observationalModel":114,"timePerspective":114,"maskingInfo":116},"NON_RANDOMIZED","PARALLEL",null,"TREATMENT",{"masking":117,"maskingDescription":114,"whoMasked":114},"NONE",[119,125,130],{"label":120,"type":121,"description":122,"interventionNames":123},"Monotherapy - RVU120","EXPERIMENTAL","Monotherapy dose finding arm - patient will be treated with single agent RVU120 with interpatient dose escalation to determine MTD and\u002For RP2D",[124],"Drug: RVU120",{"label":126,"type":121,"description":127,"interventionNames":128},"Combination therapy: RVU120+everolimus","Combination therapy dose finding arm - patient will be treated with RVU120 in combination therapy with everolimus",[124,129],"Drug: Everolimus (Afinitor) tablets",{"label":131,"type":121,"description":132,"interventionNames":133},"Combination therapy: RVU120+everolimus (expansion)","Expansion cohort - patient will be treated with RVU120 in combination therapy with everolimus - efficacy cohort",[124,129],[135,140],{"type":136,"name":137,"description":138,"armGroupLabels":139,"otherNames":114},"DRUG","RVU120","Experimantal - RVU120",[126,131,120],{"type":136,"name":141,"description":142,"armGroupLabels":143,"otherNames":114},"Everolimus (Afinitor) tablets","RVU120 + everolimus",[126,131],[145,149,152],{"name":146,"affiliation":147,"role":148},"Bożenna Dembowska-Bagińska","The Children's Memorial Health Institute","PRINCIPAL_INVESTIGATOR",{"name":150,"affiliation":147,"role":151},"Aleksander Wiśniewski","STUDY_DIRECTOR",{"name":153,"affiliation":147,"role":154},"Magdalena Kozłowska","STUDY_CHAIR",[156,161],{"name":157,"role":158,"phone":159,"phoneExt":114,"email":160},"Magdalena Kozlowska","CONTACT","+48 503 103 529","m.kozlowska@ipczd.pl",{"name":162,"role":158,"phone":163,"phoneExt":114,"email":164},"Sylwia Cichosz","+48 601 388 266","s.cichosz@ipczd.pl",[166],{"facility":167,"status":114,"city":168,"state":169,"zip":170,"country":171,"countryCode":172,"cosmosGeoPoint":173,"geoPoint":178,"contacts":179},"Instytut \"Pomnik - Centrum Zdrowia Dziecka\", Centrum Wsparcia Pediatrycznych Badań Klinicznych","Warsaw","Masovian Voivodeship","04-730","Poland","PL",{"type":174,"coordinates":175},"Point",[176,177],21.01178,52.22977,{"lat":177,"lon":176},[180,181],{"name":153,"role":158,"phone":114,"phoneExt":114,"email":160},{"name":146,"role":148,"phone":114,"phoneExt":114,"email":114},{"type":183,"investigatorFullName":184,"investigatorTitle":185,"investigatorAffiliation":5,"oldNameTitle":114,"oldOrganization":114},"SPONSOR_INVESTIGATOR","Bożenna Dembowska Bagińska","Professor",[187],{"name":188,"class":189},"Ryvu Therapeutics SA","INDUSTRY","100659571","phase-1-study-of-cdk8-inhibitor-rvu120-in-combination-with-everolimus-in-children-with-recurrent-or-progressive-group-3-or-4-medulloblastoma-100659571",false,"NCT07865130","Study of CDK8 Inhibitor RVU120 in Combination With Everolimus in Children With Recurrent or Progressive Group 3 or 4 Medulloblastoma","Phase I Study of CDK8 Inhibitor RVU120 in Combination With Everolimus in Children With Recurrent or Progressive Group 3 or 4 Medulloblastoma","MEDWAY","Inclusion Criteria:\n\n* Diagnosis: Recurrent\u002Fprogressive 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 \\\u003C4 years must have received systemic chemotherapy (CSI not required).\n* Age: 3 to ≤18 years.\n* Ability to swallow capsules\u002Ftablets required.\n* BSA: 0.4-2.5 m².\n* 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.\n* 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\u002FTBI\u002F≥50% pelvis ≥42 days; focal RT ≥14 days - Autologous transplant ≥6 months - Growth factors ≥7 days (PEG ≥14 days)\n* Organ function: Adequate marrow, liver, and renal function per protocol thresholds. Neurologic status: Stable deficits ≥1 week; seizures controlled; no enzyme-inducing anticonvulsants.\n* Performance: KPS\u002FLPS ≥60. Wheelchair-mobile patients considered ambulatory.\n* Pregnancy prevention: Effective contraception required.\n* Consent: Ability to understand and sign informed consent\u002Fassent.\n\nExclusion Criteria:\n\n* Pregnancy\u002Flactation - Pregnant or lactating patients. Negative serum pregnancy test required for patients of childbearing potential.\n* 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\u002Fconcurrent malignancies that may affect safety or efficacy assessment.\n* Concurrent therapy: any anticancer or investigational therapy; corticosteroids allowed only if stable or decreasing ≥7 days; strong CYP1A2\u002FCYP3A4\u002F3A5 inducers\u002Finhibitors 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 \\\u003C21 days before enrollment (everolimus); hereditary galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption.\n* Recent major surgery - Major surgery including tumor biopsy \\\u003C14 days before enrollment. Minor neurosurgical procedures (VP shunt, cyst fenestration, central line placement) allowed.\n* Malabsorption - Conditions requiring supplementation or significant bowel\u002Fstomach resection preventing adequate RVU120 absorption.\n* Prior CDK8 or mTOR inhibitors - Prior therapy with CDK8 inhibitors or mTOR inhibitors (everolimus, sirolimus, temsirolimus).\n* Inability to comply - Patients unable or unwilling to adhere to study visits, assessments, drug administration, or required restrictions.","ALL","3 Years","18 Years",{"count":202,"type":203},48,"ESTIMATED","INTERVENTIONAL",[206],"PHASE1","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.",[209,210],"Medulloblastoma Recurrent","Medulloblastoma",[212],"recurrent or progressive G3 or G4 medulloblastoma","NOT_YET_RECRUITING","2026-10-02",{"date":216,"type":217},"2026-10-08","ACTUAL",{"date":219,"type":203},"2026-09",{"date":221,"type":203},"2033-06",{"name":184,"class":6},1]