A Phase 1 interventional study of Everolimus and Laboratory Biomarker Analysis in CNS Embryonal Tumor, Not Otherwise Specified, Malignant Glioma and Recurrent Atypical Teratoid/Rhabdoid Tumor, sponsored by Pediatric Brain Tumor Consortium. Completed at 12 sites in United States. Open to participants aged 1 Year to 21 Years. Per ClinicalTrials.gov, last updated 2021-08-27.
Sponsored by Pediatric Brain Tumor Consortium · Phase 1, Interventional, and Treatment
Among 10 studies testing everolimus in Glioma — 2 open to participants now, 2 under way, none of them phase 3. Everolimus · Glioma.
Among the 10 studies testing everolimus in Glioma, this one is the 7th largest by enrollment, is the only one that started in 2018, is one of 4 in phase 1, and was the 6th registered.
1,452 studies on the registry are indexed under Glioma; 349 are open to participants now.
This study's enrollment of 22 is below the median of 32 across 1,075 interventional studies indexed under Glioma.
Browse Glioma studies →2 of the 10 studies testing everolimus in Glioma are open now, in 6 countries. Each count lists the studies.
Everolimus: first FDA approval 2009 (AFINITOR), first EMA approval 2009. What it is approved for, and how studies give it, is on its page →
Of the 267 Glioma studies recruiting now, 164 (61%) set no upper age limit and 57 (21%) stop at 75 or younger; 63 take children under 18; 15 take healthy volunteers.
This study: 1 Year to 21 Years · all sexes · no healthy volunteers.
The full table on the hub →10 studies; the count open now beside each. This study's row is marked.
First in 2009; this study’s year is marked. 1 started in 2018.
Median enrollment 23 across the 10 interventional studies. Of the 7 that completed or were terminated, 6 (86%) have results posted.
None of the 10 has an industry lead sponsor. The 9 most frequent:
Pediatric Brain Tumor Consortium is the lead sponsor of 31 studies on the registry; none are open to participants now.
Of its 5 completed or terminated interventional studies of FDA-regulated products, 5 (100%) have results posted.
Pediatric Brain Tumor Consortium has 5 studies filed under Glioma — fewer than ten, so there is no comparison to draw.
None of the studies under way reaches primary completion within a year.
Among the 10 studies testing everolimus in Glioma, from their registry updates:
Nothing recorded among them since 2026-09-25.
This phase I trial studies the side effects and best dose of ribociclib and everolimus and to see how well they work in treating patients with malignant brain tumors that have come back or do not respond to treatment. Ribociclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as everolimus, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ribociclib and everolimus may work better at treating malignant brain tumors.
PRIMARY OBJECTIVES:
I. To estimate the maximum tolerated dose (MTD) and/or the recommended phase II dose (RP2D) of ribociclib and everolimus in children with refractory or recurrent central nervous system (CNS) tumors. (Phase I) II. To describe the toxicity profile and define the dose-limiting toxicities (DLTs) of ribociclib and everolimus in children with refractory or recurrent CNS tumors. (Phase I) III. To characterize the pharmacokinetics of ribociclib and everolimus in children with refractory or recurrent CNS tumors, and the potential for drug-drug interactions between the two compounds in this population. (Phase I) IV. To characterize ribociclib concentrations in tumor, and plasma in children with refractory or recurrent CNS malignancies undergoing neurosurgical procedures. (Surgical Study)
SECONDARY OBJECTIVES:
I. To describe the response rate of relapsed and refractory malignant brain tumors to ribociclib and everolimus in the context of a phase I study. (Phase I) II. To explore the effect of ribociclib treatment on Ki-67 by immunohistochemistry (IHC) by comparing archival and post-treatment tumor tissue. (Surgical Study)
TERTIARY OBJECTIVES:
I. To increase knowledge of the genomic landscape of treatment-refractory pediatric CNS tumors, including mechanisms of resistance and response.
OUTLINE: This is a dose-escalation study.
Patients receive ribociclib orally (PO) once daily (QD) on days 1-21 of course 1 and subsequent courses and days 2-21 of course 2, and everolimus PO QD on days 3-28 of course 1 and days 1-28 of subsequent courses. Patients who are undergoing surgery also receive ribociclib PO QD on days 7-10 before surgery. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity. Patients with stable disease after 13 courses may continue receiving ribociclib and everolimus every 28 days for up to 13 additional courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Body surface area (BSA)
PHASE I (STRATUM 1): Patients with progressive DIPG, as defined by progressive neurologic abnormalities or worsening neurologic status not explained by causes unrelated to tumor progression (e.g., anticonvulsant or toxicity wean, electrolyte disturbances, sepsis, hyperglycemia, etc.), OR an increase in the bi-dimensional measurement, taking as a reference the smallest disease measurement recorded since last treatment, OR the appearance of a new tumor lesion since diagnosis
Please note:
SURGICAL STUDY (STRATUM 2): Patients must have recurrent or refractory disease with a histological diagnosis at either the time of diagnosis or at the time of recurrence of one of the following:
SURGICAL STUDY (STRATUM 2): Patients for whom surgical intervention is clinically indicated (gross total resection or sub-total resection) at recurrence and are amenable to receiving ribociclib for 7 ? 10 days prior to resection
BSA
Biologic or agent (anti-neoplastic): patient must have recovered from any acute toxicity potentially related to the agent and received their last dose of the investigational or biologic agent >= 7 days prior to study enrollment
Patients must have had their last fraction of:
Neurologic status
Performance status
Patients of childbearing or child fathering potential must be willing to use a medically acceptable form of while being treated on this study; Highly effective contraception methods include:
Combination of any of the two following
Exclusion Criteria:
Patients who are receiving any other anticancer or or/and anti-neoplastic therapies, including chemotherapy, immunotherapy, target therapy, biological response modifiers
Patient is currently receiving any of the following medications and cannot be discontinued 7 days prior to enrollment:
Clinically significant active cardiac disease, uncontrolled heart disease and/or a history of cardiac dysfunction including any of the following:
Long QT syndrome or known family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:
12-lead (ECG), any of the following cardiac parameters:
Hypertension defined as:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.
Studies often ask for 60 or 70 and above. Your doctor gives the score.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Relapsed and refractory
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CYP3A (CYP3A4) inhibitors and inducers
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Karnofsky performance status (KPS)
A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.
Studies often ask for 60 or 70 and above. Your doctor gives the score.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patients receive ribociclib PO QD on days 1-21 of course 1 and subsequent courses and days 2-21 of course 2, and everolimus PO QD on days 3-28 of course 1 and days 1-28 of subsequent courses. Patients who are undergoing surgery also receive ribociclib PO QD on days 7-10 before surgery. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity. Patients with stable disease after 13 courses may continue receiving ribociclib and everolimus every 28 days for up to 13 additional courses in the absence of disease progression or unacceptable toxicity.
Drug: Everolimus · Other: Laboratory Biomarker Analysis · Other: Pharmacological Study · Drug: Ribociclib
Given PO
Also known as: 42-O-(2-Hydroxy)ethyl Rapamycin, Afinitor, Certican, RAD 001, RAD001, Votubia, Zortress
Correlative studies
Correlative studies
Given PO
Also known as: Kisqali, LEE-011, LEE011
Maximum Tolerated Dose of Ribociclib and Everolimus
Defined as the highest dose level at which six patients have been treated with at most one patient experiencing a dose limiting toxicity (DLT) and the next higher dose level has been determined to be too toxic. Will be estimated using a Rolling-6 phase I design. Only patients who are evaluable for DLT will be consider for estimating of Maximum Tolerated Dose. Patient who were enrolled under Surgical cohort but received sufficient study defined treatment would also be evaluable for DLT.
Time frame: 4 weeks
Average Tumor and Plasma Concentrations of Ribociclib for the Surgical Study
Average tumor Ribociclib concentrations will be compared to plasma concentrations. The mean tumor-to-plasma ratio of Ribociclib at the time of surgery will be described.
Time frame: Surgical study: Prior to starting ribociclib (day -7 or -10), prior to ribociclib dose on days -5 & -2, day 0, and at the time of surgery
Objective Responses (Complete Response + Partial Response)
Number of patients with sustained objective responses will be reported by stratum and dose. Objective response refers to at least 50% reduction in 2 dimensional measurements of the tumor. In order to count towards this objective, any response needs to be sustained for at least 8 weeks.
Time frame: Up to 2 years
Percent Change in ki67 Between Archival and Post-treatment Tissue
For the surgical study, Ki67 will be evaluated in paired pre-treatment tumor (diagnostic) and post-treatment tumor (recurrent) tissue in consenting patients to assess percent change. The percent of Ki67 in tumor tissues will be measured and the result is presented as the percent of Ki67 in post-treatment tumor minus the percent of Ki67 measured in pre-treatment tumor.
Time frame: Up to 2 years
Ribociclib AUC (Area Under the Plasma Concentration Versus Time Curve) as Obtained From the Patients Who Received Phase I Defined Treatment
Ribociclib plasma concentration-time data obtained from patients who received Phase I defined treatment will be modeled using compartmental approaches to estimate the AUC (hr\*μM) for each dose level on days 1 and 17 of course 1. Patients who were enrolled in the Surgical stratum but subsequently received Phase I defined treatment with PK data available will also be included in the analysis population. 5 patients from surgical stratum received dose level 1 treatment.
Time frame: Pre-dose, 1, 2, 4, 8, 24, 32 (day 1 course 1 only), & 48 (day 1 course 1 only) hours after dose on days 1 and 17 of course 1.
Everolimus AUC (Area Under the Plasma Concentration Versus Time Curve) as Obtained From the Phase I Study
Everolimus plasma concentration-time data obtained from patients who received Phase I defined treatment will be modeled using compartmental approaches to estimate the AUC (hr\*nM) for each dose level on day 17 of course 1 and day 1 of course 2. Patients who were enrolled in the Surgical stratum but subsequently received Phase I defined treatment with PK data available will also be included in the analysis population. 5 patients from surgical stratum received dose level 1 treatment.
Time frame: Pre-dose, 0.5 (course 2 only), 1, 1.5 (course 2 only), 2, 4, 6 (course 2 only), 8, 24 hours after dose on day 17 of course 1, and day 1 of course 2.
Ribociclib Half-Life as Obtained From the Phase 1 Study
Ribociclib plasma concentration-time data obtained from patients received Phase I defined treatment will be modeled using compartmental approaches to estimate the half-life (hrs) for each dose level on days 1 and 17 of course 1. Patients who were enrolled in the Surgical stratum but subsequently received Phase I defined treatment with PK data available will also be included in the analysis population. 5 patients from surgical stratum received dose level 1 treatment.
Time frame: Pre-dose, 1, 2, 4, 8, 24, 32 (day 1 course 1 only), & 48 (day 1 course 1 only) hours after dose on days 1 and 17 of course 1.
Everolimus Half Life as Obtained From the Phase 1 Study
Everolimus plasma concentration-time data obtained from patients received Phase I defined treatment will be modeled using compartmental approaches to estimate the half-life (hrs) for each dose level on day 17 of course 1 and day 1 of course 2. Patients who were enrolled in the Surgical stratum but subsequently received Phase I defined treatment with PK data available will also be included in the analysis population. 5 patients from surgical stratum received dose level 1 treatment.
Time frame: Pre-dose, 0.5 (course 2 only), 1, 1.5 (course 2 only), 2, 4, 6 (course 2 only), 8, & 24 hours after dose on day 17 of course 1, and day 1 of course 2
This is Phase I and Surgical study for children with retinoblastoma protein 1 (Rb1) positive recurrent or refractory central nervous system tumors. Patients were enrolled at Pediatric Brain Tumor Consortium member institutions. The first patient was enrolled on 03/13/2018 and the last patient was enrolled on 11/18/2019. Patients who were enrolled under Surgical study may also be eligible to receive subsequent Phase I defined treatment and evaluable for DLT.
| Milestone | Phase I, Dose Level 1 | Phase I, Dose Level 2 | Surgical |
|---|---|---|---|
| Started | 13 | 3 | 5 |
| Received treatment | 12 | 3 | 5 |
| Completed | 11 | 1 | 5 |
| Not completed | 2 | 2 | 0 |
| Withdrew: Adverse event | 0 | 2 | 0 |
| Withdrew: Withdrawal by subject | 2 | 0 | 0 |
Defined as the highest dose level at which six patients have been treated with at most one patient experiencing a dose limiting toxicity (DLT) and the next higher dose level has been determined to be too toxic. Will be estimated using a Rolling-6 phase I design. Only patients who are evaluable for DLT will be consider for estimating of Maximum Tolerated Dose. Patient who were enrolled under Surgical cohort but received sufficient study defined treatment would also be evaluable for DLT.
| mg/m^2/day | DLT Evaluable Set |
|---|---|
| Ribociclib | 120 |
| Everolumus | 1.2 |
Average tumor Ribociclib concentrations will be compared to plasma concentrations. The mean tumor-to-plasma ratio of Ribociclib at the time of surgery will be described.
| ratio | Surgical |
|---|---|
| Average Tumor and Plasma Concentrations of Ribociclib for the Surgical Study | 14.6 (2.22 to 53.4) |
Number of patients with sustained objective responses will be reported by stratum and dose. Objective response refers to at least 50% reduction in 2 dimensional measurements of the tumor. In order to count towards this objective, any response needs to be sustained for at least 8 weeks.
| Participants | Phase I, Dose Level 1 | Phase I, Dose Level 2 | Surgical |
|---|---|---|---|
| Objective Responses (Complete Response + Partial Response) | 0 | 0 | 0 |
For the surgical study, Ki67 will be evaluated in paired pre-treatment tumor (diagnostic) and post-treatment tumor (recurrent) tissue in consenting patients to assess percent change. The percent of Ki67 in tumor tissues will be measured and the result is presented as the percent of Ki67 in post-treatment tumor minus the percent of Ki67 measured in pre-treatment tumor.
| Change of Percentage of Ki67 in Tumor | Surgical |
|---|---|
| Percent Change in ki67 Between Archival and Post-treatment Tissue | -20 (-35 to -5) |
Ribociclib plasma concentration-time data obtained from patients who received Phase I defined treatment will be modeled using compartmental approaches to estimate the AUC (hr\*μM) for each dose level on days 1 and 17 of course 1. Patients who were enrolled in the Surgical stratum but subsequently received Phase I defined treatment with PK data available will also be included in the analysis population. 5 patients from surgical stratum received dose level 1 treatment.
| hr*uM | Dose Level 1, Day 1 of Course 1 | Dose Level 1, Day 17 of Course 1 | Dose Level 2, Day 1 of Course 1 | Dose Level 2, Day 17 of Course 1 |
|---|---|---|---|---|
| Ribociclib AUC (Area Under the Plasma Concentration Versus Time Curve) as Obtained From the Patients Who Received Phase I Defined Treatment | 3.96 (2.6 to 11.2) | 10.3 (5.3 to 18.7) | 12.0 (5.4 to 13.4) | 10.15 (9.6 to 10.7) |
Everolimus plasma concentration-time data obtained from patients who received Phase I defined treatment will be modeled using compartmental approaches to estimate the AUC (hr\*nM) for each dose level on day 17 of course 1 and day 1 of course 2. Patients who were enrolled in the Surgical stratum but subsequently received Phase I defined treatment with PK data available will also be included in the analysis population. 5 patients from surgical stratum received dose level 1 treatment.
| hr*nM | Dose Level 1, Day 17 of Course 1 | Dose Level 1, Day 1 of Course 2 | Dose Level 2, Day 17 of Course 1 | Dose Level 2, Day 1 of Course 2 |
|---|---|---|---|---|
| Everolimus AUC (Area Under the Plasma Concentration Versus Time Curve) as Obtained From the Phase I Study | 201 (52.7 to 399) | 80.1 (29.8 to 146) | 147.5 (119 to 176) | 59 (42.5 to 75.5) |
Ribociclib plasma concentration-time data obtained from patients received Phase I defined treatment will be modeled using compartmental approaches to estimate the half-life (hrs) for each dose level on days 1 and 17 of course 1. Patients who were enrolled in the Surgical stratum but subsequently received Phase I defined treatment with PK data available will also be included in the analysis population. 5 patients from surgical stratum received dose level 1 treatment.
| hours | Dose Level 1, Day 1 of Course 1 | Dose Level 1, Day 17 of Course 1 | Dose Level 2, Day 1 of Course 1 | Dose Level 2, Day 17 of Course 1 |
|---|---|---|---|---|
| Ribociclib Half-Life as Obtained From the Phase 1 Study | 11.7 (8.0 to 18.0) | 8.9 (7.3 to 17.3) | 8.5 (8.4 to 13.9) | 7.5 (5.5 to 9.5) |
Everolimus plasma concentration-time data obtained from patients received Phase I defined treatment will be modeled using compartmental approaches to estimate the half-life (hrs) for each dose level on day 17 of course 1 and day 1 of course 2. Patients who were enrolled in the Surgical stratum but subsequently received Phase I defined treatment with PK data available will also be included in the analysis population. 5 patients from surgical stratum received dose level 1 treatment.
| hours | Dose Level 1, Day 17 of Course 1 | Dose Level 1, Day 1 of Course 2 | Dose Level 2, Day 17 of Course 1 | Dose Level 2, Day 1 of Course 2 |
|---|---|---|---|---|
| Everolimus Half Life as Obtained From the Phase 1 Study | 13.5 (8.5 to 23.1) | 14.5 (6.9 to 23.9) | 11.2 (9.0 to 13.3) | 11.5 (7.3 to 15.6) |
Collected over Up to 2 years after starting treatment. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Phase I, Dose Level 1 | 5/12 (41.7%) | 6/12 (50%) | 12/12 (100%) |
| Phase I, Dose Level 2 | 0/3 (0%) | 1/3 (33.3%) | 3/3 (100%) |
| Surgical | 0/5 (0%) | 1/5 (20%) | 5/5 (100%) |
| Event | Phase I, Dose Level 1 | Phase I, Dose Level 2 | Surgical |
|---|---|---|---|
| VomitingGastrointestinal disorders | 1/12 | 1/3 | 0/5 |
| Enterocolitis infectiousInfections and infestations | 0/12 | 1/3 | 0/5 |
| Depressed level of consciousnessNervous system disorders | 1/12 | 0/3 | 1/5 |
| Disease progressionGeneral disorders | 2/12 | 0/3 | 0/5 |
| SeizureNervous system disorders | 2/12 | 0/3 | 0/5 |
| Muscle weakness left-sidedMusculoskeletal and connective tissue disorders | 1/12 | 0/3 | 0/5 |
| Tumor hemorrhageNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 1/12 | 0/3 | 0/5 |
| DECREASED VISUAL FIELDSNervous system disorders | 1/12 | 0/3 | 0/5 |
| Edema cerebralNervous system disorders | 1/12 | 0/3 | 0/5 |
| Glossopharyngeal nerve disorderNervous system disorders | 1/12 | 0/3 | 0/5 |
| Event | Phase I, Dose Level 1 | Phase I, Dose Level 2 | Surgical |
|---|---|---|---|
| Lymphocyte count decreasedInvestigations | 4/12 | 3/3 | 4/5 |
| Neutrophil count decreasedInvestigations | 5/12 | 2/3 | 5/5 |
| White blood cell decreasedInvestigations | 6/12 | 3/3 | 4/5 |
| AnemiaBlood and lymphatic system disorders | 4/12 | 1/3 | 4/5 |
| NauseaGastrointestinal disorders | 4/12 | 2/3 | 0/5 |
| Alanine aminotransferase increasedInvestigations | 4/12 | 2/3 | 1/5 |
| Cholesterol highInvestigations | 4/12 | 2/3 | 1/5 |
| PEDIATRIC HYPERTENSIONVascular disorders | 0/12 | 2/3 | 0/5 |
| FatigueGeneral disorders | 6/12 | 1/3 | 0/5 |
| Platelet count decreasedInvestigations | 3/12 | 1/3 | 2/5 |
All patients who are eligible for the study.
| Age, Continuous(years) | Phase I, Dose Level 1 | Phase I, Dose Level 2 | Surgical | Total |
|---|---|---|---|---|
| Median | 10.4 (7.1 to 20.4) | 8.6 (3.9 to 15.9) | 10.8 (7.2 to 17.1) | 10.4 (3.9 to 20.4) |
| Sex: Female, Male(Participants) | Phase I, Dose Level 1 | Phase I, Dose Level 2 | Surgical | Total |
|---|---|---|---|---|
| Female | 5 | 1 | 1 | 7 |
| Male | 8 | 2 | 4 | 14 |
| Ethnicity (NIH/OMB)(Participants) | Phase I, Dose Level 1 | Phase I, Dose Level 2 | Surgical | Total |
|---|---|---|---|---|
| Hispanic or Latino | 1 | 0 | 1 | 2 |
| Not Hispanic or Latino | 7 | 3 | 3 | 13 |
| Unknown or Not Reported | 5 | 0 | 1 | 6 |
| Race (NIH/OMB)(Participants) | Phase I, Dose Level 1 | Phase I, Dose Level 2 | Surgical | Total |
|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 |
| Asian | 0 | 0 | 1 | 1 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 |
| Black or African American | 1 | 1 | 0 | 2 |
| White | 8 | 2 | 3 | 13 |
| More than one race | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 4 | 0 | 1 | 5 |
| Region of Enrollment(participants) | Phase I, Dose Level 1 | Phase I, Dose Level 2 | Surgical | Total |
|---|---|---|---|---|
| United States | 13 | 3 | 5 | 21 |
PDFs hosted by the registry, ClinicalTrials.gov.
Ran from Jan 2018 to primary completion in Apr 2020, 26 months.
Results were first posted in Aug 2021, 1 year 4 months after primary completion.
Of 166 non-industry phase 1 interventional studies under Glioma, half reached primary completion within 59 months of starting (the median), counting those still running; a quarter within 36 and three quarters within 87. This study's 26 months is below that.
Counting every sponsor, half of 213 studies reached it within 59 months; a quarter within 36 and three quarters within 88.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Aug 2021. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Everolimus · Ribociclib
Pediatric Brain Tumor Consortium