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New treatment option for High Grade Glioma
Official title Study of Ribociclib and Everolimus in HGG and DIPG or Ribociclib and Temozolomide in DHG, H3G34-mutant
ClinicalTrials.gov ID: NCT05843253
What this study is testing
What is Ribociclib?
Ribociclib is an investigational medicine, given as an once-daily pill taken by mouth, being studied as a potential treatment for high grade glioma.
Also referred to as Kisqali.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- 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.
- Phase 2: a mid-size study of how well it works
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 12 to 39
You may be able to join if
- TarGeT-A study strata definitions Part1: Initial Feasibility Study for the combination of ribociclib PfOS formulation with everolimus: Enrollment on...
- Stratum A: Patients with localized, intracranial, non-pontine, and non-thalamic HGG (who do not meet criteria for strata C-D)
- Stratum B: Patients with DIPG
- Stratum C: Patients with primary thalamic, spinal cord, and/or secondary/radiation-related HGG.
- Stratum D: Patients with metastatic/disseminated HGG, multifocal HGG, and/or gliomatosis cerebri who received CSI. Stratum E
You likely can't join if
- Pregnant or Breast-Feeding Pregnant or breast-feeding women will not be entered on this study due to known potential risks of fetal and teratogenic...
- Combined estrogen and progesterone containing hormonal contraception associated with inhibition of ovulation.
- Progesterone-only hormonal contraception associated with inhibition of ovulation.
- Intra Uterine Device (IUD)
- Intra Uterine hormone releasing system
- Bilateral tubal occlusion
See the full eligibility criteria
Who can join
- TarGeT-A study strata definitions Part1: Initial Feasibility Study for the combination of ribociclib PfOS formulation with everolimus: Enrollment on this cohort will be limited to patients aged \<21 years with primary...
- Stratum A: Patients with localized, intracranial, non-pontine, and non-thalamic HGG (who do not meet criteria for strata C-D)
- Stratum B: Patients with DIPG
- Stratum C: Patients with primary thalamic, spinal cord, and/or secondary/radiation-related HGG.
- Stratum D: Patients with metastatic/disseminated HGG, multifocal HGG, and/or gliomatosis cerebri who received CSI. Stratum E
- Stratum E: Patients with localized DHG, H3G34-mutant.
- already met to enroll on TarGeT-SCR (central molecular and histopathologic screening) based on: 1.1) Age: patients must be ≥12 months and ≤39 years of age at the time of enrollment on TarGeT-SCR. For the Part 1 Initial...
- For the diagnosis of DIPG, patients must have a tumor with pontine epicenter and diffuse involvement of at least 2/3 of the pons, with histopathology, consistent with diffuse WHO grade 2-4 glioma
- All other HGGs must be WHO grade 3 or 4. 1.3) Disease status: There are no disease status requirements for enrollment
- Patients without measurable disease are eligible.
- Patients with metastatic or multifocal disease or gliomatosis cerebri who received upfront CSI are eligible
- Patients with a primary spinal HGG are eligible
- Patients with secondary, radiation-related HGG are eligible.
- for assignment to TarGeT-A, for all strata: 2.1) Presence of at least one relevant actionable somatic alteration, detailed here:
- Pathogenic alterations presumed to cause activation of cell cycle:
- Amplification of CDK4 or CDK6
- Deletion of CDKN2A, CDKN2B, or CDKN2C
- Amplification of CCND1 or CCND2
- Pathogenic alterations presumed to cause activation of the PI3K/mTOR pathway:
- Deletion or mutation of PTEN
- Mutation or amplification of PIK3CA
- Mutation of PIK3R1
- Deletion or mutation of TSC1 or TSC2
- Patients with evidence of homozygous (biallelic) RB1 loss by sequencing are excluded from TarGeT-A
- Patients whose tumors harbor other alterations suspected to activate the cell cycle and/or PI3K/mTOR pathway could potentially also be eligible, but only following consensus recommendation by the international...
- For Stratum E: H3G34 (R/V) mutation 2.2) Performance Level: Karnofsky ≥ 50% for patients \> 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of ag. Patients who are unable to walk because of paralysis, but who...
- Surgery, RT, dexamethasone are permissible. Temozolomide administered concurrently with RT is permissible. Avastin/bevacizumab use is permitted given the last dose was administered \> 21 days prior to enrollment. No...
- Patients must have received photon or proton RT.
- Patients must have started RT \< 42 calendar days from initial diagnosis defined as the date of diagnostic biopsy or resection. If a patient underwent 2 upfront surgeries (e.g., biopsy then resection or debulking), this...
- RT delivered via photon or proton beam, must have been administered at a standard dose including (54 Gy in 30 fractions for DIPG, 54-59.4 Gy in 30-33 fractions), 45 Gy-54 Gy for primary spinal disease, and/or 36 Gy-39.6...
- Patients must enroll and start treatment 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. 2.4) Organ Function...
- Peripheral absolute neutrophil count (ANC) ≥ 1000/mm3
- Platelet count ≥ 100,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
- Hemoglobin \>8 g/dL (may be transfused) 2.4.2) Adequate Renal Function Defined as:
- Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2 OR
- Maximum serum creatinine based on (Schwartz et al. J. Peds, 106:522, 1985) age/gender as follows: 1 to \< 2 years=0.6 mg/dL for males and females; 2 to \< 6 years=0.8 mg/dL for males and females; 6 to \< 10 years= 1.0...
- Total bilirubin must be ≤ 1.5 times institutional upper limit of normal for age
- AST(SGOT)/ALT(SGPT) ≤ 3 times institutional upper limit of normal
- Serum albumin ≥ 2g/dL 2.4.4) Adequate Cardiac Function Defined as:
- Ejection fraction of ≥ 50% by echocardiogram
- QTc ≤ 450 msec (by Bazett formula) 2.4.5) Adequate Neurologic Function Defined as: Patients with seizure disorder may be enrolled if well-controlled on anticonvulsants that are not strong inducers or inhibitors of...
What rules you out
- Pregnant or Breast-Feeding Pregnant or breast-feeding women will not be entered on this study due to known potential risks of fetal and teratogenic adverse events as seen in animal/human studies. Pregnancy tests must be...
- Combined estrogen and progesterone containing hormonal contraception associated with inhibition of ovulation.
- Progesterone-only hormonal contraception associated with inhibition of ovulation.
- Intra Uterine Device (IUD)
- Intra Uterine hormone releasing system
- Bilateral tubal occlusion
- Vasectomized partner
- Sexual abstinence (avoiding having heterosexual intercourse) The following contraceptive measures are NOT considered effective
- Progesterone-only hormonal contraception (birth control pill) that that does NOT stop ovulation
- Male or female condom with or without spermicide
- Cap, diaphragm or sponge with spermicide
- Concomitant Medications
- Patients receiving corticosteroids are eligible. The use of corticosteroids must be reported.
- Patients who are currently receiving another investigational drug are not eligible.
- Patients who are currently receiving other anti-cancer agents are not eligible, with the exception of temozolomide given concurrently with RT only.
- Patients who are receiving enzyme inducing anticonvulsants that are strong inducers or inhibitors of CYP3A4/5 are not eligible.
- Patients who are receiving strong inducers or inhibitors of CYP3A4/5 are not eligible and should be avoided from 14 days prior to enrollment to the end of the study.
- Patients who are receiving medications known to prolong QTc interval are not eligible.
- Patients who are receiving therapeutic anticoagulation with warfarin or other coumadin-derived anticoagulants are not eligible. Therapy with heparin, low molecular weight heparin (LMWH), or fondaparinux is allowed as...
- Patients who have an uncontrolled infection are not eligible.
- Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study are not eligible.
- Patients with known clinically significant active malabsorption syndrome or other condition that could affect absorption are not eligible.
- Patients with prior or ongoing clinically significant medical or psychiatric condition that, in the investigator's opinion, could affect the safety of the subject, or could impair the assessment of study results are not...
The study team makes the final eligibility decision.
Where it's taking place
- Aurora, Colorado, United States
- Washington D.C., District of Columbia, United States
- Chicago, Illinois, United States
- Boston, Massachusetts, United States
- Ann Arbor, Michigan, United States
- Durham, North Carolina, United States
- Cincinnati, Ohio, United States
- Columbus, Ohio, United States
- Philadelphia, Pennsylvania, United States
- Houston, Texas, United States
- Seattle, Washington, United States
- Randwick, New South Wales, Australia
- South Brisbane, Queensland, Australia
- Melbourne, Victoria, Australia
- Perth, Western Australia, Australia
- Toronto, Ontario, Canada
- Montreal, Quebec, Canada
- Heidelberg, Baden-Wurttemberg, Germany
- Auckland, Grafton, New Zealand
- London, United Kingdom
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 12 months to 39 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Aurora, Colorado, United States; Washington D.C., District of Columbia, United States; Chicago, Illinois, United States; Boston, Massachusetts, United States; Ann Arbor, Michigan, United States; Durham, North Carolina, United States and 14 more location(s). Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.