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Mitogen-activated Protein Kinase (MAPK) Inhibitor

Trametinib for Pediatric Brain Tumor

Phase 2
Waitlist Available
Led By Sébastien Perreault, MD
Research Sponsored by St. Justine's Hospital
Eligibility Criteria Checklist
Specific guidelines that determine who can or cannot participate in a clinical trial
Must have
Patients must be aged ≥ 1 month (corrected age) to ≤ 25 years when starting trametinib
Participants must belong to one of the specified groups: NF1 with progressing/refractory LGG, NF1 with PN, progressing/refractory LGG with KIAA 1549-BRAF fusion, progressing/refractory glioma with activation of the MAPK/ERK pathway who do not meet criteria for other study groups
Must not have
Participants previously treated with a MEK inhibitor who showed less than stable disease during treatment
Patients with severe and uncontrollable medical diseases, chronic liver disease, uncontrolled intercurrent illness, known HIV infection, hepatitis B or C
Timeline
Screening 3 weeks
Treatment Varies
Follow Up 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.
Awards & highlights
No Placebo-Only Group

Summary

This trial will study the response rate of pediatric brain tumors to oral administration of the drug trametinib. A total of 150 patients will be recruited, and the study will also explore the molecular mechanisms behind tumor development, progression and resistance to treatment.

Who is the study for?
This trial is for children and young adults aged 1 month to 25 years with specific brain tumors or neurofibromatosis who have not responded to at least one prior treatment. Eligible participants must be able to take oral medication, agree to use contraception if applicable, and commit to study requirements like MRI scans.
What is being tested?
The trial tests Trametinib's effectiveness in treating pediatric patients with glioma or plexiform neurofibroma that involves the MAPK/ERK pathway. It's an open-label phase 2 study where patients receive daily doses of Trametinib over cycles lasting 28 days each.
What are the potential side effects?
Trametinib may cause side effects such as skin rash, diarrhea, fatigue, nausea and vomiting, abdominal pain, hypertension, bleeding events, heart problems (like reduced ejection fraction), vision changes, muscle aches or weakness.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below
Select...
I am between 1 month and 25 years old and starting trametinib treatment.
Select...
I have a specific type of progressing brain tumor or nerve tumor.
Select...
I can do most activities but may need help.
Select...
My organ and bone marrow functions are normal.
Select...
I can swallow and keep down pills without significant stomach issues affecting absorption.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:
Select...
My condition worsened while on a MEK inhibitor treatment.
Select...
I do not have severe illnesses like uncontrolled liver disease, HIV, or hepatitis.
Select...
My tumor has a positive BRAF V600E mutation.
Select...
My heart's pumping ability is below normal, or I have a long QT interval.

Timeline

Screening ~ 3 weeks
Treatment ~ Varies
Follow Up ~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 trial's timeline: 3 weeks for screening, Varies for treatment, and 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. for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.
Primary study objectives
Objective Response Rate
Secondary study objectives
Determination of the Serum Level of Trametinib.
Evaluation of the Quality of Life During Treatment.
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability).
+3 more
Other study objectives
Comparison of responses with RECIST 1.1 and volumetric measurement for plexiform neurofibroma
Investigation and correlation of biological features to tumor response.
Neurocognitive assessment of NF1 patients between 1 and 42 months using the Bayley Scales of Infant and Toddlers Development, Third Edition (Bailey-III).
+4 more

Side effects data

From 2021 Phase 2 trial • 206 Patients • NCT02034110
47%
Pyrexia
36%
Fatigue
33%
Anaemia
33%
Nausea
33%
Decreased appetite
28%
Rash
22%
Headache
22%
Constipation
22%
Pneumonia
22%
Chills
22%
Dyspnoea
19%
Dizziness
19%
Hypoalbuminaemia
19%
Vomiting
19%
Diarrhoea
19%
Hyponatraemia
17%
Dysphagia
17%
Blood alkaline phosphatase increased
17%
Back pain
14%
Aspartate aminotransferase increased
14%
Hypocalcaemia
14%
Dry mouth
14%
Hyperglycaemia
14%
Arthralgia
14%
Oedema peripheral
14%
White blood cell count decreased
14%
Insomnia
14%
Hypotension
11%
Hypokalaemia
11%
Haemoptysis
11%
Alanine aminotransferase increased
11%
Dry skin
11%
Hypothyroidism
11%
Pruritus
11%
Visual impairment
11%
Weight decreased
11%
Cough
8%
Productive cough
8%
Upper respiratory tract infection
8%
Rash maculo-papular
8%
Mucosal inflammation
8%
Hypercalcaemia
8%
Gastrooesophageal reflux disease
8%
Pleural effusion
8%
Night sweats
8%
Asthenia
8%
Ejection fraction decreased
8%
Electrocardiogram QT prolonged
8%
Gamma-glutamyltransferase increased
8%
Neutrophil count decreased
8%
Neck pain
6%
Rhinorrhoea
6%
Seborrhoeic keratosis
6%
Haematochezia
6%
Skin lesion
6%
Acute kidney injury
6%
Pulmonary embolism
6%
Thrombocytopenia
6%
Atrial fibrillation
6%
Stomatitis
6%
Rhinitis allergic
6%
Tachycardia
6%
Abdominal pain upper
6%
Hyperuricaemia
6%
Leukopenia
6%
Sinusitis
6%
Urinary tract infection
6%
Polyneuropathy
6%
Haematuria
6%
Neutropenia
6%
Ear pain
6%
Abdominal pain
6%
Feeling cold
6%
Non-cardiac chest pain
6%
Pain
6%
Fungal infection
6%
Nasopharyngitis
6%
Blood creatinine increased
6%
Blood urea increased
6%
Neutrophil count increased
6%
Hypomagnesaemia
6%
Myalgia
6%
Neuropathy peripheral
6%
Proteinuria
6%
Nasal congestion
6%
Pneumonitis
6%
Palmar-plantar erythrodysaesthesia syndrome
3%
Pelvic infection
3%
Rhabdomyolysis
3%
Tinnitus
3%
Sepsis
3%
Malaise
3%
Cataract
3%
Dermatitis acneiform
3%
Erythema nodosum
3%
Femoral neck fracture
3%
Hyperglycaemic hyperosmolar nonketotic syndrome
3%
Aortic thrombosis
3%
Pollakiuria
3%
Hypophosphataemia
3%
Flushing
3%
Oesophageal stenosis
3%
Atrioventricular block first degree
3%
Photophobia
3%
Dehydration
3%
Toothache
3%
Oral candidiasis
3%
Urinary retention
3%
Alopecia
3%
Skin mass
3%
Aspiration
3%
Vision blurred
3%
Oedema
3%
Depression
3%
Folliculitis
3%
Staphylococcal infection
3%
Clavicle fracture
3%
Aphasia
3%
Cardiac ventricular thrombosis
3%
Stress cardiomyopathy
3%
Oral pain
3%
Clostridium difficile infection
3%
Diverticulitis
3%
Pneumonia aspiration
3%
Pneumonia necrotising
3%
Wound infection
3%
Hyperkalaemia
3%
Rib fracture
3%
Bladder transitional cell carcinoma
3%
Facial nerve disorder
3%
Hypertension
3%
Paralysis recurrent laryngeal nerve
3%
Syncope
3%
Hallucination
3%
Pulmonary haematoma
3%
Sinus bradycardia
3%
Dry eye
3%
Abdominal distension
3%
Dyspepsia
3%
Gait disturbance
3%
Nodule
3%
Xerosis
3%
Conjunctivitis
3%
Tooth infection
3%
Procedural pain
3%
Blood creatine phosphokinase increased
3%
Platelet count decreased
3%
Weight increased
3%
Flank pain
3%
Muscular weakness
3%
Musculoskeletal chest pain
3%
Pain in extremity
3%
Hypoaesthesia
3%
Paraesthesia
3%
Anxiety
3%
Sleep disorder
3%
Dysphonia
3%
Epistaxis
3%
Upper-airway cough syndrome
3%
Wheezing
3%
Erythema
100%
80%
60%
40%
20%
0%
Study treatment Arm
Anaplastic Thyroid Cancer (ATC) (On-Treatment)
Biliary Tract Cancer (BTC) (On-Treatment)
Gastrointestinal Stromal Tumor (GIST) (On-Treatment)
Low Grade (WHO G1/G2) Glioma (LGG) (On-Treatment)
Anaplastic Thyroid Cancer (ATC) (Post-treatment Survival Follow-up)
Gastrointestinal Stromal Tumor (GIST) (Post-treatment Survival Follow-up)
Low Grade (WHO G1/G2) Glioma (LGG) (Post-treatment Survival Follow-up)
Adenocarcinoma of the Small Intestine (ASI) (Post-treatment Survival Follow-up)
Hairy Cell Leukemia (HCL) (Post-treatment Survival Follow-up)
High Grade (WHO G3/G4) Glioma (HGG) (On-Treatment)
Hairy Cell Leukemia (HCL) (On-Treatment)
Multiple Myeloma (MM) (On-Treatment)
High Grade (WHO G3/G4) Glioma (HGG) (Post-treatment Survival Follow-up)
Adenocarcinoma of the Small Intestine (ASI) (On-Treatment)
Biliary Tract Cancer (BTC) (Post-treatment Survival Follow-up)
Multiple Myeloma (MM) (Post-treatment Survival Follow-up)

Awards & Highlights

No Placebo-Only Group
All patients enrolled in this study will receive some form of active treatment.

Trial Design

4Treatment groups
Experimental Treatment
Group I: Progressing/refractory low grade-glioma, KIAA1549-BRAF fusionExperimental Treatment1 Intervention
Patients presenting with a progressing/refractory low-grade glioma with a KIAA1549-BRAF fusion.
Group II: Progressing/Refractory central nervous system (CNS) glioma.Experimental Treatment1 Intervention
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.
Group III: Neurofibromatosis Type 1 (NF1) with low-grade gliomaExperimental Treatment1 Intervention
Patients presenting with Neurofibromatosis Type 1 (NF1) and a progressing/refractory low-grade glioma.
Group IV: Neurofibromatosis Type 1 (NF1) with Plexiform NeurofibromaExperimental Treatment1 Intervention
Patients presenting with Neurofibromatosis Type 1 (NF1) and a plexiform neurofibroma
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Trametinib
2014
Completed Phase 2
~1630

Find a Location

Who is running the clinical trial?

Montreal Children's Hospital of the MUHCOTHER
30 Previous Clinical Trials
116,497 Total Patients Enrolled
St. Justine's HospitalLead Sponsor
200 Previous Clinical Trials
86,029 Total Patients Enrolled
CHU de Quebec-Universite LavalOTHER
172 Previous Clinical Trials
109,561 Total Patients Enrolled
Sébastien Perreault, MDPrincipal InvestigatorSt. Justine's Hospital

Media Library

Trametinib (Mitogen-activated Protein Kinase (MAPK) Inhibitor) Clinical Trial Eligibility Overview. Trial Name: NCT03363217 — Phase 2
Plexiform Neurofibroma Research Study Groups: Progressing/refractory low grade-glioma, KIAA1549-BRAF fusion, Neurofibromatosis Type 1 (NF1) with Plexiform Neurofibroma, Neurofibromatosis Type 1 (NF1) with low-grade glioma, Progressing/Refractory central nervous system (CNS) glioma.
Plexiform Neurofibroma Clinical Trial 2023: Trametinib Highlights & Side Effects. Trial Name: NCT03363217 — Phase 2
Trametinib (Mitogen-activated Protein Kinase (MAPK) Inhibitor) 2023 Treatment Timeline for Medical Study. Trial Name: NCT03363217 — Phase 2
~29 spots leftby Mar 2027