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Study of Ribociclib and Everolimus in HGG and DIPG
The goal of this study is to determine the efficacy of the study drugs 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. The main question the study aims to answer is whether the combination of ribociclib and everolimus can prolong the life of patients diagnosed with HGG, including DIPG.
Study details:
This is a multicenter, international, phase II 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 (Part 2). The study will include a feasibility cohort (Part 1) to identify the dose of ribociclib PfOS (Powder for Oral Suspension) that is safe and tolerable in combination with everolimus. Efficacy for 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 II dose (RP2D) of the combination of ribociclib and everolimus in patients with metastatic disease who received upfront craniospinal irradiation (stratum D). Protocol therapy with the maintenance combination of ribociclib and everolimus 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. 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).
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
Exclusion criteria
Eligibility
Age eligible for study : 12 and older
Healthy volunteers accepted : No
Gender eligible for study: All
Things to know
Study dates
Study start: 2024-08-22
Primary completion: 2028-08-28
Study completion finish: 2034-08-28
Study type
TREATMENT
Phase
PHASE2
Trial ID
NCT05843253
Intervention or treatment
DRUG: Ribociclib
DRUG: Everolimus
Conditions
- • High Grade Glioma
- • Diffuse Intrinsic Pontine Glioma
- • Anaplastic Astrocytoma
- • Glioblastoma
- • Glioblastoma Multiforme
- • Diffuse Midline Glioma, H3 K27M-Mutant
- • Metastatic Brain Tumor
- • WHO Grade III Glioma
- • WHO Grade IV Glioma
Find a site
Closest Location:
Sydney Children's Hospital
Research sites nearby
Select from list below to view details:
Sydney Children's Hospital
Randwick, New South Wales, Australia
Queensland Children's Hospital
South Brisbane, Queensland, Australia
Perth Children's Hospital
Perth, Western Australia, Australia
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Participant Group/Arm | Intervention/Treatment |
---|---|
EXPERIMENTAL: Stratum A (n=40)
| DRUG: Ribociclib
|
EXPERIMENTAL: Stratum B (n=40)
| DRUG: Ribociclib
|
EXPERIMENTAL: Stratum C (n=6-12)
| DRUG: Ribociclib
|
EXPERIMENTAL: Stratum D (n=6-12)
| DRUG: Ribociclib
|
What is the study measuring?
Primary outcome
Primary Outcome Measure | Primary Outcome Description | Primary Outcome Time Frame |
---|---|---|
Progression-Free Survival (PFS) in HGG (Part 2, Stratum A) | To assess the efficacy of ribociclib and everolimus in pediatric and young adult patients newly diagnosed with HGG by estimating the distribution of PFS compared to molecularly-stratified and matched historical controls. | From date on treatment until date of Progressive Disease or death due to any cause or date of last follow-up, assessed up to 60 months |
Overall Survival (OS) in DIPG (Part 2, Stratum B) | To assess the efficacy of ribociclib and everolimus in pediatric and young adult patients newly diagnosed with DIPG by estimating the distribution of OS compared to molecularly-stratified and matched historical controls. | From date on treatment until date of death due to any cause or date of last follow-up, assessed up to 60 months |
Establish MTD and RP2D of ribociclib and everolimus (Part 2, Stratum D) | To identify the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of the combination of ribociclib and everolimus given to patients with metastatic HGG who have received craniospinal irradiation CSI. | Completion of Cycle 1 (28 days) |
Number of participants with ribociclib and everolimus-related adverse events as assessed by CTCAE v5.0 (Part 1- initial feasibility study) | Identify the safe dose of ribociclib powder for oral solution (PfOS) formulation in combination with everolimus that is feasible in pediatric patients with newly-diagnosed HGG, including DIPG, with cell cycle and/or PI3K/mTOR pathway alterations. This will be achieved by calculating the number of participants with, as well as frequency and severity of, ribociclib and everolimus-related Adverse Events as assessed by CTCAE v5.0 in the first 6-12 patients enrolled | Completion of Cycle 1 (28 days) |
Secondary outcome
Secondary Outcome Measure | Secondary Outcome Description | Secondary Outcome Time Frame |
---|---|---|
Overall Survival in HGG | Determine distribution of OS for pediatric and young adult patients newly-diagnosed with HGG which harbor cell cycle and/or PI3K/mTOR pathway alterations treated with post-RT ribociclib and everolimus. | From date on treatment until date of death due to any cause or date of last follow-up, assessed up to 60 months |
Objective Response Rate (ORR) in HGG | Evaluate the radiographic objective response rate (ORR) defined as complete response (CR) + partial response (PR) in pediatric and young adult patients newly diagnosed with HGG treated with the combination of ribociclib and everolimus. | From Day 1 of protocol treatment through 30 days following end of protocol treatment |
Objective Response Rate (ORR) in DIPG | Evaluate the radiographic objective response rate (ORR) defined as complete response (CR) + partial response (PR) in pediatric and young adult patients newly diagnosed with DIPG treated with the combination of ribociclib and everolimus. | From Day 1 of protocol treatment through 30 days following end of protocol treatment |
Number of participants with ribociclib and everolimus-related adverse events as assessed by CTCAE v5.0 | Assess and further characterize the safety and toxicity of post-RT combination of ribociclib and everolimus in pediatric and young adult patients newly diagnosed with HGG, including DIPG. This will be achieved by calculating the number of participants with, as well as frequency and severity of, ribociclib and everolimus-related Adverse Events as assessed by CTCAE v5.0. | From Day 1 of protocol treatment through 30 days following end of protocol treatment |
Evaluate Health-Related Quality of Life Outcomes | Evaluate health-related quality of life outcomes of pediatric and young adult patients newly-diagnosed with HGG, including DIPG, treated with combination of ribociclib and everolimus, by patient and/or parent reporting at key timepoints in therapy using the patient reported outcomes measurement information system (PROMIS) survey. | At the end of Cycles 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 (each cycle is 28 days) |
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