A Phase 2 interventional study of Trametinib in Low-grade Glioma, Plexiform Neurofibroma and Central Nervous System Glioma, sponsored by St. Justine's Hospital. Active, not recruiting at 7 sites in Canada. Open to participants aged 1 Month to 25 Years. Per ClinicalTrials.gov, last updated 2026-04-24.
Sponsored by St. Justine's Hospital · Phase 2, Interventional, and Treatment
This is a phase 2, open-label, interventional clinical trial that will study the response rate of pediatric glioma and plexiform neurofibroma (PN) to oral administration of trametinib. Patients meeting all inclusion criteria for a given study group will receive the study medication at a daily dose of 0.025 mg/kg up to a total of 18 cycles, in 28-day cycles. A total of 150 patients will be recruited as part of this clinical study.
Patients aged between 1 month (corrected age) and 25 years old will be eligible, in order to include a maximum of patients affected by low-grade glioma (LGG) and PN. This study includes four groups: patients with neurofibromatosis type 1 (NF1) and LGG, NF1 patients with PN, patients with LGG with a B-Raf Serine/Threonine-protein Kinase/Proto-oncogene Encoding B-Raf (BRAF) fusion and patients with glioma of any grade with activation of the Mitogen-activated Protein Kinase/Extracellular Signal-regulated Kinases (MAPK/ERK) pathway. All patients except patients with PN must have failed at least one line of treatment.
The study will also explore the molecular mechanisms behind tumor development, progression and resistance to treatment. Furthermore, this study will also explore important aspects for patients with brain tumors by including assessment of quality of life and neuropsychological evaluation.
63 studies on the registry are indexed under Neurofibroma, Plexiform; 19 are open to participants now.
This study's enrollment of 114 is above the median of 36 across 43 interventional studies indexed under Neurofibroma, Plexiform.
Browse Neurofibroma, Plexiform studies →St. Justine's Hospital is the lead sponsor of 156 studies on the registry; 27 are open to participants now.
Counted across the registry records on this site, refreshed daily.
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.
7 Previous MRI At least two previous MRIS fro Group 1, 3, 4 and one previous MRI for Group 2 must be available for central review.
8. Prior therapy Participants must have failed at least one including chemotherapy and/or radiation therapy except for plexiform neurofibroma (since there is no recognized standard treatment for his tumor).
9. Prior therapy toxicity Patients must have recovered to grade ≤ 1 from acute toxic effects of all prior chemotherapy, immunotherapy or radiotherapy prior to enrollment except for alopecia and non-treatment related clinically insignificant laboratory abnormalities. prior to starting trametinib. Toxicities will be graded as per the National Cancer Institute (CTCAE), version 5.0
10. Prior therapy timeline Participants having previously received a chemotherapy agent(s) and/or radiation must conform to the timeline described below. There is no limitation on the number of previous treatments or cycles received.
An interval of at least 48 hours for short-acting colony stimulating factor agents and 10 days interval for long-acting colony stimulating factor agents are required prior to starting trametinib.
11. Patients must have a life expectancy of greater than 6 months.
12. Performance level Patients must have a performance status corresponding to a Lansky/ score ≥50.
13. Organ Function Requirements
Participants must have normal organ and marrow function as defined below:
Blood pressure must be smaller or equal to the 95th percentile for patient's age, height and gender.
For uniformity reasons, the ULN for ALT will be 45 U/L in this study
14. Reproductive status Children of childbearing and child-fathering potential must agree to use adequate (hormonal or barrier method of birth control; abstinence) prior to starting trametinib and for the duration of study participation. Should a female become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Males and females treated or enrolled in this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of trametinib administration. Furthermore, females of (older than 10 years old for this study) must have a negative serum pregnancy test within 7 days prior to starting trametinib. A urine pregnancy test will be done according to evaluation calendar at at 30 days and at 6 months following the last does of study medications.
15. Administration of oral medication Patients must be able to ingest and retain enterally (per os, nasogastric tube or gastrostomy) administered medication and be free of any gastrointestinal abnormalities limiting the absorption of the medication. Tablets cannot be crushed. If the patient cannot swallow tablets, the liquid form should then be used.
SPECIFIC INCLUSION CRITERIA
Participants must belong to one of the following groups to be eligible.
Exclusion Criteria:
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.
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.
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.
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
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.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
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.
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).
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.
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.
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 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.
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.
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.
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.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
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.
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.
Line of therapy
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CTCAE grade
The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
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.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patients presenting with Neurofibromatosis Type 1 (NF1) and a progressing/refractory low-grade glioma.
Drug: Trametinib
Patients presenting with Neurofibromatosis Type 1 (NF1) and a plexiform neurofibroma
Drug: Trametinib
Patients presenting with a progressing/refractory low-grade glioma with a KIAA1549-BRAF fusion.
Drug: Trametinib
Patients presenting with a progressing/refractory central nervous system glioma with an activation of the MAPK/ERK pathway who do not meet criteria for inclusion in other study groups.
Drug: Trametinib
Daily administration of oral trametinib at a unique dose of 0.025 mg/kg.
Also known as: Mekinist
Objective Response Rate
Determination of the objective response rate of daily trametinib as a single agent for treatment of progressing/refractory low-grade tumors with MAPK/ERK pathway activation.
Time frame: From date of treatment start until the date of first documented progression, up to completion of treatment (504 treatment days).
Time to Progression
Time from treatment start, or censored at the date of last disease evaluation for those without progression reported. Applicable to group 1-2-3-4.
Time frame: From date of treatment start up to 3 years following completion of treatment (504 treatment days).
Progression Free Survival
Time from treatment start to the earlier of progression or death due to any cause. Participants alive without disease progression are censored at the date of last disease evaluation. Applicable to group 1-2-3-4.
Time frame: From date of treatment start up to 3 years following completion of treatment (504 treatment days).
Overall Survival
Time from treatment start to death due to any cause, or censored at date last known alive. Applicable to group 1-2-3-4.
Time frame: From date of treatment start up to 3 years following completion of treatment (504 treatment days).
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability).
Determination of the safety and tolerability of trametinib by assessment of toxicity associated with trametinib (Adverse Events (AEs), Serious Adverse Events (SAEs)). Applicable to group 1-2-3-4.
Time frame: From treatment start until 30-day follow-up visit.
Determination of the Serum Level of Trametinib.
Determination of the serum level of trametinib by assessment of the through level. Applicable to group 1-2-3-4.
Time frame: At Cycle 1 day 22 and at tumor progression OR on Day 1 of Cycle 16 (each cycle is 28 days long).
Evaluation of the Quality of Life During Treatment.
Evaluation of the quality of life during treatment with the PedsQL cancer/brain tumor modules. Applicable to group 1-2-3-4.
Time frame: At screening, week 13, week 25, week 37, week 49, week 61 and at the end of treatment day 504.
Neurocognitive assessment of NF1 patients between 1 and 42 months using the Bayley Scales of Infant and Toddlers Development, Third Edition (Bailey-III).
Determine if there are cognitive changes in patients with NF1 during treatment with trametinib. The areas of development assessed to calculate the composite score are: cognition, communication, physical, social/emotional and adaptative. This scale ranges from a score of 40 to 160 with a mean score of 100, where higher scores are desirable.
Time frame: At study inclusion and at the end of treatment (up to treatment day 504).
Neurocognitive assessment of NF1 patients between 2 years and 6 years using the Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV).
Determine if there are cognitive changes in patients with NF1 during treatment with trametinib.The areas of cognition assessed to calculate the composite score are: verbal comprehension, visual spatial, fluid reasoning, working memory and processing speed. This scale ranges from a score of 40 to 160 with a mean score of 100, where higher scores are desirable.
Time frame: At study inclusion and at the end of treatment (up to treatment day 504).
Neurocognitive assessment of NF1 patients between 6 years and 16 years and 11 months using the Wechsler Intelligence Scale for Children, Fifth Edition (WISC-V).
Determine if there are cognitive changes in patients with NF1 during treatment with trametinib.The areas of cognition assessed to calculate the composite score are: verbal comprehension, visual spatial, fluid reasoning, working memory and processing speed. This scale ranges from a score of 40 to 160 with a mean score of 100, where higher scores are desirable.
Time frame: At study inclusion and at the end of treatment (up to treatment day 504).
Neurocognitive assessment of NF1 patients between 16 years 11 months and 25 years using the Wechsler Adult Intelligence Scale, Fourth Edition (WAIS-IV).
Determine if there are cognitive changes in patients with NF1 during treatment with trametinib.The areas of cognition assessed to calculate the composite score are: verbal comprehension, perceptual reasoning, working memory and processing speed. This scale ranges from a score of 40 to 160 with a mean score of 100, where higher scores are desirable.
Time frame: At study inclusion and at the end of treatment (up to treatment day 504).
Response rate of patients with refractory glioma with activation of the MAPK pathway other than BRAF fusion and NF1
Determination of trametinib usefulness in patients with refractory glioma with activation of the MAPK pathway other than BRAF fusion and NF1. Applicable to group 4
Time frame: At study inclusion and at the end of treatment (up to treatment day 504).
Comparison of responses with RECIST 1.1 and volumetric measurement for plexiform neurofibroma
Comparison of the best response rate using the RECIST 1.1 criteria and volumetric measurement. Applicable to group 2.
Time frame: At the achievement of best response to treatment up to treatment day 504.
Investigation and correlation of biological features to tumor response.
Gene expression profiling on fresh frozen tissue and mutational analysis on paraffin-embedded tissue. Circulating tumor DNA (ctDNA) evolution through treatment.
Time frame: Within 14 days prior to treatment start for investigations of tumor tissue. At screening, week 13, week 25, week 37, week 49, week 61, at the end of treatment day 504 and every 6 months up to 3 years for ctDNA evaluation.
This study is active, not recruiting, as verified in Apr 2026. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Trametinib