Trials / Recruiting

RecruitingNCT05843253

Study of Ribociclib and Everolimus in HGG and DIPG or Ribociclib and Temozolomide in DHG, H3G34-mutant

Phase 2 Study of Ribociclib-Containing Post-Radiotherapy Combinations in Pediatric and Young Adult Patients Newly Diagnosed With High-Grade Glioma, Including Diffuse Intrinsic Pontine Glioma: Ribociclib and Everolimus for HGG/DIPG Which Harbor Alterations of the Cell Cycle and/or PI3K/mTOR Pathways AND Ribociclib and Temozolomide for DHG, H3G34-mutant

Status: Recruiting
Phase: Phase 2
Study type: Interventional
Enrollment: 120 (estimated)

Sponsor: Nationwide Children's Hospital · Academic / Other
Sex: All
Age: 12 Months – 39 Years
Healthy volunteers: Not accepted

Summary

The goal of this study is to determine the efficacy of the 1) ribociclib and everolimus to treat pediatric and young adult patients newly diagnosed with a high-grade glioma (HGG), including DIPG, that have genetic changes in pathways (cell cycle, PI3K/mTOR) that these drugs target or 2) ribociclib and temozolomide to treat pediatric and young adult patients newly diagnosed with diffuse hemispheric glioma (DHG), H3G34-mutant. The main question the study aims to answer is whether the combinations of ribociclib and everolimus or ribociclib and temozolomide can prolong the life of patients diagnosed with HGG/DIPG or DHG H3G34-mutant.

Detailed description

This is a multicenter, international, phase 2 study of post-radiotherapy (RT) combination of ribociclib and everolimus to treat pediatric, adolescent, and young adult patients newly diagnosed with HGG and DIPG that harbor alterations of the cell cycle and/or PI3K/mTOR pathways to assess treatment efficacy (Stratum A-D Part 2). The study will include a feasibility cohort (Strata A-D, Part 1) to identify the dose of ribociclib PfOS (Powder for Oral Suspension) that is safe and tolerable in combination with everolimus. Efficacy for Strata A-D Part 2 study will be defined by progression-free survival (PFS; HGG \[stratum A\]) and Overall Survival (OS; DIPG \[stratum B\]), with key longitudinal biomarker correlatives. Outcomes among patients with primary thalamic, spinal cord, and/or secondary (radiation related) HGG (strata C) will be descriptively analyzed. Objective radiographic response rates and agent-specific toxicities will also be assessed, with a feasibility cohort to determine the recommended phase 2 dose (RP2D) of the combination of ribociclib and everolimus in patients with metastatic disease who received upfront craniospinal irradiation (stratum D). The study was amended in October 2025 to also include an additional stratum, Stratum E, which will serve patients with localized DHG, H3G34-mutant with the combination of ribociclib and temozolomide. As most DHG, H3G34-mutant tumors are MGMT promoter methylated and receive temozolomide as part of standard of care, we are studying the adjuvant combination of ribociclib and temozolomide following upfront RT. Stratum E will open with a Phase 1 Run-In to determine the RP2D of ribociclib PfOS formulation in combination with temozolomide in patients newly-diagnosed with DHG, H3G34-mutant post-RT, with PK testing. Once the RP2D is determined, patients with localized DHG, H3G34-mutant will be enrolled on the Stratum E efficacy expansion cohort to descriptively assess survival outcomes, with similar longitudinal biomarker correlatives to the other strata. Protocol therapy with the maintenance combination of either 1) ribociclib and everolimus or 2) ribociclib and temozolomide must begin no later than 35 calendar days post-completion of RT. The earliest patients can begin protocol treatment is 28 calendar days post-completion of RT. Each cycle will be 28 days in duration and treatment can continue up to a total of 26 cycles. For Strata A-D, Ribociclib will be given orally once daily for 3 weeks (days 1-21), with one week off. Everolimus will be given orally daily continuously (days 1-28). For Stratum E, Ribociclib will be given orally once daily for 3 weeks (days 1-21), and temozolomide will be given days 1-5 for the first 13 cycles (Year 1), and ribociclib alone will be given orally once daily for 3 weeks (days 1-21) for the subsequent 13 cycles (Year 2).

Conditions

Interventions

Type	Name	Description
DRUG	Ribociclib	Ribociclib PO qd on days 1-21
DRUG	Everolimus	Everolimus PO qd on days 1-28
DRUG	Temozolomide (TMZ)	Temozolomide PO qd on days 1-5 for the first 13 cycles

Timeline

Start date: 2024-08-22
Primary completion: 2029-08-31
Completion: 2034-08-28
First posted: 2023-05-06
Last updated: 2026-03-20

Locations

21 sites across 7 countries: United States, Australia, Canada, Germany, Netherlands, New Zealand, United Kingdom

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT05843253. Inclusion in this directory is not an endorsement.