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Low-grade GliomaPhase 2NCT03363217

Trametinib for Pediatric Neuro-oncology Patients With Refractory Tumor and Activation of the MAPK/ERK Pathway.

A Phase 2 study testing Trametinib in people with Low-grade Glioma and Plexiform Neurofibroma, run by St. Justine's Hospital at 7 sites in Canada.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 1 month to 25 years
What is being tested?
Trametinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
114 participants
Where
7 sitesCanada
Study dates
16 Aug 2018to 1 Mar 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 month to 25 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Signed written informed consent Prior to study participation, written informed consent from participants, or in the case of minors, written permission (informed consent) from parents, guardians, or legally acceptable representatives must be obtained according to local laws and regulations.
  • Assent Assent from minor participants should be obtained per local laws and regulations and should be documented in accordance with local requirements.
  • Study activities compliance. Participants must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study, including disease assessment by contrast-enhanced MRI.
  • Age Patient must be aged ≥ 1 month (corrected age) to ≤ 25 years when starting trametinib.
  • Study group Participants must belong to one of the following groups to be eligible. Group 1: NF1 with progressing/refractory LGG Group 2: NF1 with PN Group 3: Progressing/refractory LGG with KIAA 1549-BRAF fursion Group 4: Progressing/refractory glioma with activation of the MPAK/ERK pathway who do not meet criteria for other study groups
  • Tumor Tissue Sample Tumor tissue will be required for all patients (minimally paraffin-embedded tissue block and additionally fresh frozen tissue [if available]). Patients with NF1 and LGG or PN can still be enrolled without tissue if no surgery or biopsy was conducted.
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  • 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 line of treatment 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 Common Terminology Criteria for Adverse Events (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 28 days after the last dose of a myelosuppressive chemotherapy, and at least 42 days after the last dose of Nitrosoureas is required prior to starting trametinib.
  • An interval of at least 28 days after the last dose of any biologic agents including monoclonal antibody treatment, immunotherapy, viral therapy and other investigational agent is required prior to starting trametinib.
  • An interval of at least 84 days after the end of the radiation therapy is required prior to starting trametinib.
  • 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. Life expectancy Patients must have a life expectancy of greater than 6 months.
  • 12. Performance level Patients must have a performance status corresponding to a Lansky/Karnofsky score ≥50.
  • 13. Organ Function Requirements
  • Participants must have normal organ and marrow function as defined below:
  • Total leukocytes ≥ 3,000/µL
  • Absolute neutrophil count (ANC) ≥ 1, 000/µL
  • Hemoglobin > 80 g/l (transfusion independent within last 2 weeks prior to starting trametinib)
  • Platelet count ≥ 100,000/µL (transfusion independent within last 2 weeks prior to starting trametinib)
  • Total bilirubin ≤ 1.5 times the ULN within normal institutional limits for age
  • Alanine Aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN)*
  • Creatinine serum within normal institutional limits for age OR creatinine clearance ≥60 mL/min/1.73 m2 for participants with creatinine levels above institutional normal.
  • Creatine phosphokinase ≤ 2x ULN
  • A cardiac function defined as Corrected QT (QTcB) interval < 480 msec and LVEF ≥ lower limit of normal (LLN) by echocardiogram (ECHO).
  • 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 contraception (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 childbearing potential (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 clinically significant 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.
  • Group 1: NF1 with Progressing/Refractory LGG (42 patients).
  • Group 2: NF1 with Progressing/Refractory PN (46 patients).
  • Group 3: Progressing/Refractory LGG with KIAA1549-BRAF fusion (42 patients).
  • Group 4: Progressing/Refractory CNS Glioma with activation of the MAPK/ERK pathway who do not meet criteria of other study groups (20 patients).

Who cannot join

  • Other investigational agents Patients who are receiving any other investigational agents.
  • Cardiac exclusion criteria Patients who have an ejection fraction inferior to the institution LLN, a QTcB ≥ 480 msec or an absolute resting left ventricular ejection fraction (LVEF) of ≤ 39% are not eligible for enrollment.
  • Presence of another malignancy Patient has any other malignancy except if the other primary malignancy is neither currently clinically significant nor requiring active intervention.
  • Previous MEK inhibitor treatment Participants previously treated with a MEK inhibitor who showed less than stable disease during treatment.
  • Tumor with BRAF V600E mutation Patients with a tumor presenting a positive BRAF V600E mutation.
  • Other uncontrollable medical disease Patient has a severe and uncontrollable medical disease (i.e., uncontrolled diabetes, chronic renal disease or active uncontrolled infection), has a chronic liver disease (i.e., chronic active hepatitis and cirrhosis), uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
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  • Known HIV infection Patient has a known diagnosis of human immunodeficiency virus (HIV) infection, hepatitis B or C.
  • Previous surgery Patients who had major surgery within 2 weeks prior to starting trametinib.
  • Allergy History of allergic reactions attributed to compounds of similar chemical or biologic composition to trametinib.
  • Previous history of non-compliance Patients with a previous significant history of non-compliance to their treatment or medical regimen.
  • Pregnant or breastfeeding patients Pregnant or breastfeeding female patients are not eligible for this study.

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

Canada7 sites

  • Alberta Children's Hospital

    Calgary, Alberta, T3B 6A8

  • IWK Health Centre

    Halifax, Nova Scotia

  • CHU Sainte-Justine

    Montreal, Quebec, H3T 1C5

  • Montreal Children's Hospital

    Montreal, Quebec, H4A 3J1

  • CHU de Québec

    Québec, Quebec, G1V 4G2

  • The Hospital for Sick Children

    Toronto, Ontario, M5G 1X8

  • Children and Women's Health Centre of British Colombia

    Vancouver, British Columbia

Other trials in Canada

About this study

Official title: A Phase 2 Study of Trametinib for Patients With Pediatric Glioma or Plexiform Neurofibroma With Refractory Tumor and Activation of the MAPK/ERK Pathway.

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.

Being tested
Trametinib
Keywords
Glioma, Optic Pathway Glioma, Low grade glioma, MAPK/ERK, Plexiform Neurofibroma, Neurofibromatosis Type 1, Central Nervous System, CNS, Brain Tumor, LGG, NF1, KIAA1549-BRAF, Mitogen-activated Protein Kinase (MEK) inhibitor, Trametinib
Medical subject headings
Neurofibroma, Plexiform, Glioma, Neurofibromatosis 1, Brain Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TrametinibDrug

    Also called Mekinist

    Daily administration of oral trametinib at a unique dose of 0.025 mg/kg.

Study groups in NCT03363217
Study groupRoleWhat they receive
Neurofibromatosis Type 1 (NF1) with low-grade gliomaExperimentalPatients presenting with Neurofibromatosis Type 1 (NF1) and a progressing/refractory low-grade glioma.
Receives: Drug: Trametinib
Neurofibromatosis Type 1 (NF1) with Plexiform NeurofibromaExperimentalPatients presenting with Neurofibromatosis Type 1 (NF1) and a plexiform neurofibroma
Receives: Drug: Trametinib
Progressing/refractory low grade-glioma, KIAA1549-BRAF fusionExperimentalPatients presenting with a progressing/refractory low-grade glioma with a KIAA1549-BRAF fusion.
Receives: Drug: Trametinib
Progressing/Refractory central nervous system (CNS) glioma.ExperimentalPatients 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.
Receives: Drug: Trametinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: From date of treatment start until the date of first documented progression, up to completion of treatment (504 treatment days).

Secondary outcomes (6)

  1. 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.

    Measured: From date of treatment start up to 3 years following completion of treatment (504 treatment days).

  2. 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.

    Measured: From date of treatment start up to 3 years following completion of treatment (504 treatment days).

  3. 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.

    Measured: From date of treatment start up to 3 years following completion of treatment (504 treatment days).

  4. 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.

    Measured: From treatment start until 30-day follow-up visit.

  5. 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.

    Measured: At Cycle 1 day 22 and at tumor progression OR on Day 1 of Cycle 16 (each cycle is 28 days long).

  6. 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.

    Measured: At screening, week 13, week 25, week 37, week 49, week 61 and at the end of treatment day 504.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Dec 2017
  2. Study start16 Aug 2018
  3. Primary completion1 Mar 2027 (estimated)
  4. Study completion1 Mar 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
This trial will include 4 parallel groups. Each group will include a particular type of peripheral nerve or central nervous system tumor or mutation.
Masking
None (open label)
Enrolment
114 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03363217
Sponsor's protocol ID
Trametinib study TRAM-01
Status last verified
Apr 2026
First submitted
10 Nov 2017
Last updated
24 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Perreault S, Larouche V, Tabori U, Hawkin C, Lippe S, Ellezam B, Decarie JC, Theoret Y, Metras ME, Sultan S, Cantin E, Routhier ME, Caru M, Legault G, Bouffet E, Lafay-Cousin L, Hukin J, Erker C, Jabado N. A phase 2 study of trametinib for patients with pediatric glioma or plexiform neurofibroma with refractory tumor and activation of the MAPK/ERK pathway: TRAM-01. BMC Cancer. 2019 Dec 27;19(1):1250. doi: 10.1186/s12885-019-6442-2.

    PubMed 31881853

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Trametinib in people with Low-grade Glioma and Plexiform Neurofibroma, run by St. Justine's Hospital at 7 sites in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 37 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 24 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (time frame: From date of treatment start until the date of first documented progression, up to completion of treatment (504 treatment days).). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03363217, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2026.

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