Pediatric Low-grade GliomaPhase 1/2MIRVNCT06666348
Phase 1/2 Study of Mirdametinib + Vinblastine for Newly Diagnosed/Previously Untreated PLGG + Activation of MAPK
A Phase 1/2 study testing Mirdametinib in people with Pediatric Low-grade Glioma, run by St. Justine's Hospital at 10 sites in Canada.
Trial summary
This is a 3-part open-label study (feasibility phase, treatment phase and follow-up phase) of orally administered mirdametinib in combination with intravenous vinblastine chemotherapy in patients with PLGG with activation of MAPK pathway. Read more about this study
- Who is it for?
- Ages 2 to 25 years
- Conditions the study is for
- Pediatric Low-grade Glioma
- What is being tested?
- Mirdametinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 10 sitesCanada
- Study dates
- 12 Jan 2026to Apr 2033
- Phase
- Phase 1/2
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 2 to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Signed written informed consent prior to study participation.
- Study activities compliance: 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.
- Aged ≥ 2 years to ≤ 25 years when starting mirdametinib.
- BSA ≥ 0,40m2
- Diagnosis:
- Participants must have PLGG with NF1 gene mutation (based on clinical NIH criteria, germline NF1 mutation or molecular analysis of the tumor) or PLGG with KIAA1549-BRAF fusion (based on molecular analysis of the tumor) or PLGG with evidence of MAPK pathway alteration with the exception of patients with BRAF V600E mutation (based on molecular analysis of the tumor).
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- Tumor tissue is required (at minimum, paraffin-embedded tissue block and additionally fresh frozen tissue [if available]). Patients with NF1 and Low Grade Glioma (LGG) can still be enrolled without tissue if no surgery or biopsy was conducted.
- Baseline MRI.
- Life expectancy greater than 6 months.
- Lansky/Karnofsky score ≥ 50.
- Normal organ and marrow function (see study protocol for specifics).
- Female and male patients of fertile age must agree to use highly effective contraceptive measures.
- Must be able to ingest by mouth and retain entirely the administered medication. Mirdametinib can not be administered via nasogastric tube or gastrostomy tube.
Who cannot join
- Patients who are receiving other investigational agents.
- Cardiac: QTcB ≥ 480 msec or an absolute resting left ventricular ejection fraction (LVEF) of ≤ 49%.
- Patients who have any other malignancy, except if the other primary malignancy is neither currently clinically significant nor requiring active intervention.
- Tumor with BRAF V600E mutation.
- Patients who received previous systemic or radiotherapy treatment.
- Other severe and uncontrollable medical disease
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- Blood pressure higher than 95th percentile for patient's age, height and gender.
- Increased risk of serious retinopathy and retinal vein occlusion.
- Known diagnosis of human immunodeficiency virus infection, hepatitis B or C.
- Previous major surgery within 2 weeks.
- History of allergic reactions to compounds of similar chemical or biological composition to mirdametinib.
- Pregnant or breastfeeding.
Trial locations and contacts
10 sites in 1 country. Contact the study team or a site near you to ask about taking part.
MIRV Study Team contact
10 sites in 1 country
Canada10 sites, 10 recruiting
- Recruiting
Alberta Children's Hospital
Calgary, Alberta, T3B 6A8
Lucie Lafay-Cousin, MD, (403) 955-7272, lucie.lafay-cousin@ahs.ca
- Recruiting
Stollery Children's Hospital
Edmonton, Alberta, T6G 2E1
Liana Nobre, MD, (780) 248-1646, liana.nobre@albertahealthservices.ca
- Recruiting
Children's Hospital, London Health Sciences Centre
London, Ontario, N6A5W9
Chantel Cacciotti, MD, (519) 685-8500 ext. 52433, chantel.cacciotti@lhsc.on.ca
- Recruiting
CHU Sainte-Justine
Montreal, Quebec, H3T 1C5
Sébastien Perreault, MD, 514-345-4931 ext. 5019, s.perreault@umontreal.ca
Marie Galopin, RN, 514-345-4931 ext. 6326, marie.galopin.hsj@ssss.gouv.qc.ca
- Recruiting
Children's Hospital of Eastern Onatrio
Ottawa, Ontario, K1H 8L1
Nirav Thacker, MD, 613-737-2328, nthacker@cheo.on.ca
- Recruiting
CHU de Québec - Université Laval
Québec, Quebec, G1V 4G2
Valérie Larouche, MD, (418) 525-4444 ext. 40121, valerie.larouche.med@ssss.gouv.qc.ca
- Recruiting
CHU de Sherbrooke
Sherbrooke, Quebec, J1H 5N4
Stéphanie Vairy, MD, 819-346-1110 ext. 73068, stephanie.vairy@usherbrooke.ca
- Recruiting
The Hospital for Sick Children
Toronto, Ontario, M5G 1E8
Anthony Liu, MD, (416) 813-7654, anthony.liu@sickkids.ca
Ashley Doka, CRPC, (416) 813-7654 ext. 427327, ashley.doka@sickkids.ca
- Recruiting
Childrens and Womens Health Centre of British Columbia - British Columbia Childrens Hospital
Vancouver, British Columbia, V6H 3V4
Sylvia Cheng, MD, (604) 875-2406, sylvia.cheng@cw.bc.ca
- Recruiting
Cancer Care Manitoba
Winnipeg, Manitoba, R3E 0V9
Issai Vanan, MD, 204-787-4156, ctu_web@cancercare.mb.ca
About this study
Official title: A Phase 1/2 Study of Mirdametinib and Vinblastine for Newly Diagnosed or Previously Untreated Patients With Pediatric Low-grade Glioma and Activation of the MAPK Pathway
This is a 3-part open-label study (feasibility phase, treatment phase and follow-up phase) of orally administered mirdametinib in combination with intravenous vinblastine chemotherapy in patients with PLGG with activation of MAPK pathway.
Feasibility Phase:
Read more
The maximum tolerated/recommended phase 2 dose (MTD/RP2D) of the mirdametinib plus vinblastine combination will be assessed using a modified Rolling-6 design.
Treatment Phase:
Patients will receive mirdametinib twice daily (continuously) at a fixed dose (2mg/m2 po BID up to 4 mg BID) for a total of 13 cycles (28 days cycle). Weekly intravenous vinblastine at MTD will be given for a total of 17 cycles. If adverse events occur, two dose reductions are allowed.
Follow-up Phase:
Following the end of treatment, patients will be scheduled for a follow-up visit every 6 months for 36 months to evaluate PFS, TTP and OS.
Read the detailed description
This is a phase 1/2, open label, interventional clinical trial that will study the response rate of newly diagnosed pediatric low-grade glioma (PLGG) to oral administration of mirdametinib in combination with weekly vinblastine. Patients meeting all inclusion criteria for a given study group will receive mirdametinib twice daily (continuous) at a fixed dose (2 mg/m2 po BID up to 4 mg BID) for a total of 13 cycles (28 days cycle). Weekly intravenous vinblastine at MTD will be given for a total of 17 cycles.
The lead-in feasibility phase will be conducted to establish the maximum tolerated/recommended phase 2 dose (MTD/RP2D) of vinblastine in combination with mirdametinib combination using a modified Rolling-6 design. The established RP2D for mirdametinib (2 mg/m2 po BID up to 4 mg BID) will be used on this study. Mirdametinib will be administered on a continuous dosing schedule and de-escalated as necessary to an intermittent (3 weeks on, 1 week off) dosing schedule. Vinblastine will be escalated (or de-escalated) as necessary. Since these classes of agents do not have overlapping toxicities, the starting dose (i.e., Dose Level 0) for vinblastine is 4 mg/m2/week, which is 20% lower than the recommended single agent dose of vinblastine of 5 mg/m2/week. Dose Level 1 for vinblastine is 5 mg/m2/week and Dose Level -1 for vinblastine is 3 mg/m2/week.
Following the end of treatment, patients will be scheduled for a follow-up visit every 6 months for 36 months to evaluate PFS, TTP and OS. A total of 50 patients will be recruited as part of this clinical study.
Patients aged between 2 and 25 years old will be eligible, in order to include a maximum of patients affected by glioma. This study includes PLGG patients with neurofibromatosis type 1 (NF1) with a KIAA1549-BRAF fusion and patients with activation of the MAPK pathway with the exception of patients with a BRAFV600E mutation.
Response to treatment will be evaluated using the modified Response Assessment in Pediatric Neuro-Oncology (RAPNO), Response Assessment in Pediatric Neuro-Oncology (RANO) 1. Evaluation of quality of life will be measured using the Pediatric Quality of Life inventory (PedsQL) (Generic/Brain tumor modules).
This study will explore the genetic and epigenetic landscape of PLGG. Our biological study may include SNP array, nanoString studies, methylation array and RNAseq.
- Conditions
- Pediatric Low-grade Glioma
- Being tested
- Mirdametinib
- Keywords
- PLGG, Pediatric PLGG, Pediatric, MAPK, NF1, KIAA1549-BRAF, pediatric low-grade glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MirdametinibDrug
Also called Vinblastine
Participants will receive orally administered mirdametinib in combination with intravenous vinblastine chemotherapy
| Study group | Role | What they receive |
|---|---|---|
| Mirdametinib + IV Vinblastine | Experimental | Patients will receive oral mirdametinib twice daily (continuous) at a fixed dose (2mg/m2 PO BID, rounded to the nearest 1mg, up to a maximum of 4 mg BID) for a total of 13 cycles. Each cycle will last 28 days. Receives: Drug: Mirdametinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine maximum tolerated dose of Mirdametinib plus Vinblastine.
The maximum tolerated/recommended phase 2 dose (MTD/RP2D) of the mirdametinib plus vinblastine combination using a modified Rolling-6 design.
Measured: 3 years
Determine the objective response rate of mirdametinib plus vinblastine for PLGG with Mitogen-activated Protein Kinase (MAPK) pathway activation in treatment naïve patients.
The proportion of patients with complete (CR), major (MaR), partial (PR) and minor response (MiR) as the best response on study based on RAPNO criteria.
Response = MiR+PR+MaR+CR
Measured: 5 years
Secondary outcomes (7)
Efficacy outcome measures: Overall Survival.
Overall Survival (OS) is defined as the time from starting mirdametinib (C1D1) to death due to any cause, or censored at date last known alive. OS will be evaluated from starting mirdametinib up to the end of the 3-year follow-up. Estimated using Kaplan-Meier methods.
Measured: Up to 3 years following completion of treatment.
Efficacy outcome measures: Progression-Free Survival.
Progression-Free Survival (PFS): the time from starting mirdametinib (C1D1) to the date of first observation of radiological progression or death due to any cause. Participants alive without disease progression or death are censored at date of last disease evaluation. Estimated using Kaplan-Meier methods.
Measured: Up to 3 years following completion of treatment.
Efficacy outcome measures: Time to Progression.
Time to Progression (TTP) is defined as the time from starting mirdametinib (C1D1) to radiological progression, or censored at date of last disease evaluation for those without progression reported. Estimated using Kaplan-Meier methods.
Measured: Up to 3 years following completion of treatment.
Efficacy outcome measures: Objective Response Rate.
Objective response rate (ORR) is defined as the percentage of patients experiencing their best response on study as CR or PR or MR or SD.
Measured: Up to 3 years following completion of treatment.
Determine the safety and tolerability of the combination of mirdametinib plus vinblastine.
Adverse events (AE) and severe adverse events (SAE).
Measured: 5 years
Determine neurological changes in patients during active treatment and after completion of therapy.
Changes in neurological status will be evaluated. Standardized global assessment including motor function will be evaluated by local investigators at baseline, every six months during treatment phase and after completion of treatment. This evaluation will include assessment of weakness, coordination, and balance.
Measured: 5 years
Evaluate the quality of life during treatment.
Evaluations of quality of daily life at inclusion and every six months PedsQL (Generic/Brain tumor modules).
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2024
- Study start12 Jan 2026
- Primary completionApr 2030 (estimated)
- Study completionApr 2033 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Pediatric Low-grade GliomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is a 3-part open-label study (feasibility phase, treatment phase and follow-up phase) of orally administered mirdametinib in combination with intravenous vinblastine chemotherapy in patients with PLGG with activation of MAPK pathway. Feasibility Phase: The maximum tolerated/recommended phase 2 dose (MTD/RP2D) of the mirdametinib plus vinblastine combination will be assessed using a modified Rolling-6 design. Treatment Phase: Patients will receive mirdametinib twice daily (continuously) at a fixed dose (2mg/m2 po BID up to 4 mg BID) for a total of 13 cycles (28 days cycle). Weekly intravenous vinblastine at MTD will be given for a total of 17 cycles. If adverse events occur, two dose reductions are allowed. Follow-up Phase: Following the end of treatment, patients will be scheduled for a follow-up visit every 6 months for 36 months to evaluate PFS, TTP and OS.
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- St. Justine's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr Perreault, St. Justine's Hospital
- Investigators
- Sébastien Perreault, M.D, FRCPC, Study chair, CHU Sainte Justine, URCHOI Department
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06666348
- Sponsor's protocol ID
- MIRV
- Acronym
- MIRV
- Status last verified
- Oct 2026
- First submitted
- 9 Oct 2024
- Last updated
- 16 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data will be share with researchers upon request following publication of data analysis of trial via scientific articles.
Publications
Robinson GW, Vinitsky A, Bag AK, et al. LGG-53. RESULTS FROM THE PHASE 1 AND PHASE 1 EXPANSION COHORTS OF SJ901: A PHASE 1/2 TRIAL OF SINGLE-AGENT MIRDAMETINIB (PD-0325901) IN CHILDREN, ADOLESCENTS, AND YOUNG ADULTS WITH LOW-GRADE GLIOMA. Neuro Oncol. 2024; 26(Suppl 4):0
Gross AM MC, Warren KE, Widemann BC. Plasma and cerebrospinal fluid pharmacokinetics of selumetinib in non-human primates (NHP). Journal of Clinical Oncology. 2017; 35((15_suppl)):e14070-e14070
Lassaletta A, Scheinemann K, Zelcer SM, Hukin J, Wilson BA, Jabado N, Carret AS, Lafay-Cousin L, Larouche V, Hawkins CE, Pond GR, Poskitt K, Keene D, Johnston DL, Eisenstat DD, Krishnatry R, Mistry M, Arnoldo A, Ramaswamy V, Huang A, Bartels U, Tabori U, Bouffet E. Phase II Weekly Vinblastine for Chemotherapy-Naive Children With Progressive Low-Grade Glioma: A Canadian Pediatric Brain Tumor Consortium Study. J Clin Oncol. 2016 Oct 10;34(29):3537-3543. doi: 10.1200/JCO.2016.68.1585.
PubMed 27573663Fangusaro J, Onar-Thomas A, Young Poussaint T, Lensing S, Ligon AH, Lindeman N, Banerjee A, Kilburn LB, Lenzen A, Pillay-Smiley N, Pollack IF, Robison NJ, Partap S, Qaddoumi I, Landi D, Jones DTW, Stewart CF, Fouladi M, Dunkel IJ. A phase 2 PBTC study of selumetinib for recurrent/progressive pediatric low-grade glioma: Strata 2, 5, and 6 with long-term outcomes on strata 1, 3, and 4. Neuro Oncol. 2025 Oct 14;27(9):2415-2428. doi: 10.1093/neuonc/noaf065.
PubMed 40241281Fangusaro J, Onar-Thomas A, Young Poussaint T, Wu S, Ligon AH, Lindeman N, Banerjee A, Packer RJ, Kilburn LB, Goldman S, Pollack IF, Qaddoumi I, Jakacki RI, Fisher PG, Dhall G, Baxter P, Kreissman SG, Stewart CF, Jones DTW, Pfister SM, Vezina G, Stern JS, Panigrahy A, Patay Z, Tamrazi B, Jones JY, Haque SS, Enterline DS, Cha S, Fisher MJ, Doyle LA, Smith M, Dunkel IJ, Fouladi M. Selumetinib in paediatric patients with BRAF-aberrant or neurofibromatosis type 1-associated recurrent, refractory, or progressive low-grade glioma: a multicentre, phase 2 trial. Lancet Oncol. 2019 Jul;20(7):1011-1022. doi: 10.1016/S1470-2045(19)30277-3. Epub 2019 May 28.
PubMed 31151904Weiss BD, Wolters PL, Plotkin SR, Widemann BC, Tonsgard JH, Blakeley J, Allen JC, Schorry E, Korf B, Robison NJ, Goldman S, Vinks AA, Emoto C, Fukuda T, Robinson CT, Cutter G, Edwards L, Dombi E, Ratner N, Packer R, Fisher MJ. NF106: A Neurofibromatosis Clinical Trials Consortium Phase II Trial of the MEK Inhibitor Mirdametinib (PD-0325901) in Adolescents and Adults With NF1-Related Plexiform Neurofibromas. J Clin Oncol. 2021 Mar 1;39(7):797-806. doi: 10.1200/JCO.20.02220. Epub 2021 Jan 28.
PubMed 33507822Jones DT, Gronych J, Lichter P, Witt O, Pfister SM. MAPK pathway activation in pilocytic astrocytoma. Cell Mol Life Sci. 2012 Jun;69(11):1799-811. doi: 10.1007/s00018-011-0898-9. Epub 2011 Dec 13.
PubMed 22159586Packer RJ, Lange B, Ater J, Nicholson HS, Allen J, Walker R, Prados M, Jakacki R, Reaman G, Needles MN, et al. Carboplatin and vincristine for recurrent and newly diagnosed low-grade gliomas of childhood. J Clin Oncol. 1993 May;11(5):850-6. doi: 10.1200/JCO.1993.11.5.850.
PubMed 8487049Sievert AJ, Fisher MJ. Pediatric low-grade gliomas. J Child Neurol. 2009 Nov;24(11):1397-408. doi: 10.1177/0883073809342005.
PubMed 19841428Fangusaro J, Witt O, Hernaiz Driever P, Bag AK, de Blank P, Kadom N, Kilburn L, Lober RM, Robison NJ, Fisher MJ, Packer RJ, Young Poussaint T, Papusha L, Avula S, Brandes AA, Bouffet E, Bowers D, Artemov A, Chintagumpala M, Zurakowski D, van den Bent M, Bison B, Yeom KW, Taal W, Warren KE. Response assessment in paediatric low-grade glioma: recommendations from the Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group. Lancet Oncol. 2020 Jun;21(6):e305-e316. doi: 10.1016/S1470-2045(20)30064-4.
PubMed 32502457