Phase 1/2 Study of Mirdametinib + Vinblastine for Newly Diagnosed/Previously Untreated PLGG + Activation of MAPK

Last updated: June 8, 2026
Sponsor: St. Justine's Hospital
Overall Status: Active - Recruiting

Phase

1/2

Condition

Neurofibromatosis

Brain Cancer

Astrocytoma

Treatment

Mirdametinib

Clinical Study ID

NCT06666348
MIRV
  • Ages 2-25
  • All Genders

Study 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.

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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Signed written informed consent prior to study participation.

  • Study activities compliance: must be willing and able to comply with scheduledvisits, 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).

  • Tumor tissue is required (at minimum, paraffin-embedded tissue block andadditionally fresh frozen tissue [if available]). Patients with NF1 and Low GradeGlioma (LGG) can still be enrolled without tissue if no surgery or biopsy wasconducted.

  • 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 effectivecontraceptive 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.

Exclusion

Exclusion Criteria:

  • 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 isneither 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

  • 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 biologicalcomposition to mirdametinib.

  • Pregnant or breastfeeding.

Study Design

Total Participants: 50
Treatment Group(s): 1
Primary Treatment: Mirdametinib
Phase: 1/2
Study Start date:
January 12, 2026
Estimated Completion Date:
April 30, 2033

Study 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.

Connect with a study center

  • Alberta Children's Hospital

    Calgary, Alberta T3B 6A8
    Canada

    Active - Recruiting

  • Stollery Children's Hospital

    Edmonton, Alberta T6G 2E1
    Canada

    Active - Recruiting

  • Childrens and Womens Health Centre of British Columbia - British Columbia Childrens Hospital

    Vancouver, British Columbia V6H 3V4
    Canada

    Active - Recruiting

  • Children's Hospital, London Health Sciences Centre

    London, Ontario N6A5W9
    Canada

    Active - Recruiting

  • The Hospital for Sick Children

    Toronto, Ontario M5G 1E8
    Canada

    Active - Recruiting

  • CHU Sainte-Justine

    Montreal, Quebec H3T 1C5
    Canada

    Active - Recruiting

  • CHU de Québec - Université Laval

    Québec, Quebec G1V 4G2
    Canada

    Active - Recruiting

  • CHU de Sherbrooke

    Sherbrooke, Quebec J1H 5N4
    Canada

    Active - Recruiting

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