Mirdametinib plus vinblastine for newly diagnosed pediatric low-grade glioma with MAPK activation

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is an open-label Phase 1/2 study combining the MEK inhibitor mirdametinib with weekly intravenous vinblastine in patients with newly diagnosed pediatric low-grade glioma that has MAPK pathway activation. A feasibility lead-in using a modified Rolling-6 design will determine the maximum tolerated/recommended Phase 2 dose of the combination, with mirdametinib given continuously (2 mg/m2 twice daily up to 4 mg BID) and vinblastine given weekly. In the treatment phase patients receive 13 cycles of continuous mirdametinib (28-day cycles) and up to 17 weekly vinblastine cycles, with up to two dose reductions allowed for toxicity. After treatment, patients are followed every six months for 36 months to document progression-free survival, time to progression, and overall survival.

Why it matters

Who can join: the full rules

Inclusion Criteria:

* 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).

* 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.

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 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
* 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.

Where it's running

• Alberta Children's Hospital
  Calgary, Alberta, Canada Recruiting
• Stollery Children's Hospital
  Edmonton, Alberta, Canada Recruiting
• Childrens and Womens Health Centre of British Columbia - British Columbia Childrens Hospital
  Vancouver, British Columbia, Canada Recruiting
• Cancer Care Manitoba
  Winnipeg, Manitoba, Canada Recruiting
• Children's Hospital, London Health Sciences Centre
  London, Ontario, Canada Recruiting
• Children's Hospital of Eastern Onatrio
  Ottawa, Ontario, Canada Recruiting

Study contacts

• Study coordinator: Sébastien Perreault, M.D, FRCPC
• Email: s.perreault@umontreal.ca
• Phone: 514-345-4931

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Other studies for the same condition or treatment. Recruiting studies are listed first.

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.