Mirdametinib + Vinblastine for Pediatric Low-Grade Glioma
Phase 1/2 Study of Mirdametinib + Vinblastine for Newly Diagnosed/Previously Untreated PLGG + Activation of MAPK
Recruiting
Phase 1Phase 2Interventional Study
Pediatric Low-grade Glioma
No Placebo Group
Every participant receives an active treatment — no one gets a placebo.
Prior Safety Data
This treatment has already been tested in at least one earlier human trial.
Ready to participate?
Review the details below, then apply to join this clinical trial.
At a Glance
Age
2 – 25
Sex
Any
Trial phase
Phase 1/2
Study type
Interventional
Purpose
Treatment
Participants needed
50 (estimated)
Sponsor
St. Justine's Hospital · Other
Who this trial is looking for
This trial is looking for young patients with specific types of brain tumors called pediatric low-grade gliomas. Participants will take a medication called mirdametinib and receive vinblastine chemotherapy over several months.
Are You a Good Fit for This Trial?
You may be able to join if
I am between 2 and 25 years old.
I have been diagnosed with a pediatric low-grade glioma.
I can provide a tissue sample of my tumor.
I am able to take medicine by mouth.
I have a life expectancy of more than 6 months.
I agree to use effective birth control if I am of childbearing age.
I am willing and able to follow the study schedule and requirements.
You may not be able to join if
I am currently taking other investigational treatments.
I have a history of serious heart problems.
I have another active cancer that needs treatment.
My tumor has a BRAF V600E mutation.
I have had previous cancer treatment like chemotherapy or radiation.
I have severe medical conditions that cannot be controlled.
I have very high blood pressure.
I am pregnant or breastfeeding.
Summarized in plain language from this trial's official eligibility criteria.
The full criteria are further down this page — only the research team can
confirm whether you qualify.
Think this trial could be right for you?
Answer a few quick questions to see if you may meet the eligibility requirements.
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…
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.
Trial Locations
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Eligibility Criteria
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…
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.
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