What is the mechanism of action of this treatment?

The most common treatments for Low Grade Glioma (LGG) include MEK inhibitors like mirdametinib, which target the MAPK/ERK pathway to reduce tumor growth by inhibiting cell proliferation and survival signals. Temozolomide, an alkylating agent, works by damaging the DNA of cancer cells, leading to cell death. Radiation therapy induces DNA damage to kill cancer cells and shrink tumors. These treatments are significant for LGG patients as they specifically target the molecular and cellular mechanisms driving tumor growth, potentially leading to better control of the disease and improved patient outcomes.

What side effects are associated with this type of intervention?

MEK inhibitors, such as Mirdametinib, commonly cause side effects including rash, diarrhea, fatigue, and peripheral edema. Other potential adverse effects may include nausea, vomiting, and increased liver enzymes. These side effects are consistent with those observed in other treatments targeting the MAPK/ERK pathway to reduce tumor growth in low-grade glioma.

What prior FDA approvals exist?

As of now, there are no specific FDA-approved MEK inhibitors like Mirdametinib for the treatment of Low Grade Glioma. However, MEK inhibitors such as trametinib and cobimetinib have been approved for other cancers, including melanoma, which also involve the MAPK/ERK pathway. These drugs work by inhibiting the MEK enzyme, thereby reducing tumor growth. The ongoing research and trials, such as the one involving Mirdametinib, aim to explore the efficacy of similar treatments for Low Grade Glioma.

What other types of research exist?

Promising novel alternatives to Mirdametinib for Low Grade Glioma patients include: 1) Selumetinib, another MEK inhibitor that has shown efficacy in pediatric low-grade gliomas. 2) Dabrafenib and Trametinib combination, particularly for patients with BRAF V600E mutations. 3) Everolimus, an mTOR inhibitor, which has been studied for its potential in treating various brain tumors, including gliomas. These alternatives target similar pathways and have shown potential in clinical trials.

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MEK inhibitor

Mirdametinib for Brain Tumor

Phase 1 & 2

Recruiting

Led By Anna Vinitsky, MD, MS

Research Sponsored by St. Jude Children's Research Hospital

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

For Phase 1: Projected to be ≥ 2 years and < 25 years at the time of study enrollment

Participant must be ≥ 2 years and < 25 years of age at the time of enrollment

Must not have

Participant with a known history of liver disease or known hepatic or biliary abnormalities

Participants with uncontrolled glaucoma

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 1 month after start of mirdametinib treatment

Awards & highlights

No Placebo-Only Group

Summary

This trial tests mirdametinib, a drug that blocks cancer growth signals, in children and young adults with specific types of brain tumors. It aims to see if the drug is safe and effective in slowing down or stopping tumor growth. Mirdametinib has been tested in studies for neurofibromatosis type 1-related plexiform neurofibromas.

Who is the study for?

This trial is for children, adolescents, and young adults up to 25 years old with a specific type of brain tumor called low-grade glioma. They must have relapsed or progressed after previous treatments but can't have had any MEK inhibitors before (except in certain cases). Participants need proper organ function and no history of liver disease or other serious medical conditions that could affect the study.

What is being tested?

The trial is testing Mirdametinib, a drug designed to penetrate the brain and target tumors by inhibiting a protein called MEK. It's an open-label Phase 1/2 study, meaning both researchers and participants know what treatment is being given, aimed at seeing how well this drug works in pediatric patients with low-grade glioma.

What are the potential side effects?

Potential side effects are not listed explicitly here but based on similar medications; they may include digestive issues, skin rash, fatigue, vision changes due to retinal problems, increased blood pressure, liver enzyme changes indicating potential liver damage.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am between 2 and 25 years old at the time of joining the study.

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I am between 2 and 24 years old.

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I can do most activities and am expected to live at least 6 more weeks.

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I have never taken MEK inhibitor medications.

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My cancer has worsened or returned after my last treatment.

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I have a diagnosis or suspicion of a low-grade brain tumor.

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I have enough tumor tissue available for testing.

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My last radiation treatment was over 3 months ago.

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My bone marrow and organs are functioning well.

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My low-grade glioma diagnosis has been confirmed by a central pathology review.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a known liver disease or liver-related condition.

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I have glaucoma that is not well-managed.

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I have a history of serious lung disease.

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I am not on any other cancer treatments and have no ongoing major side effects.

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I have a known eye condition that could lead to severe retinal problems.

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My tumor is high-grade or has certain genetic mutations.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 1 month after start of mirdametinib treatment

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~1 month after start of mirdametinib treatment

This trial's timeline: 3 weeks for screening, Varies for treatment, and 1 month after start of mirdametinib treatment for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Characterize the maximum plasma concentration and area under the concentration-time curve (AUC0-8h) of mirdametinib.

Describe the toxicity profile of mirdametinib by cohort.

Phase 1: Determine the safety and tolerability of mirdametinib dosed twice daily on a continuous schedule in pediatric patients with progressive or recurrent low-grade glioma.

+5 more

Secondary study objectives

Longitudinal change in academic achievement, by cohort

Longitudinal change in adaptive behavior, by cohort

Executive Function

+11 more

Side effects data

From 2023 Phase 1 & 2 trial • 6 Patients • NCT05054374

33%

CPK increased

33%

Lymphocyte count decreased

17%

Alkaline phosphatase increased

17%

Aspartate aminotransferase increased

100%

80%

60%

40%

20%

Study treatment Arm

Arm 1, Part 1 - Mirdametinib in Combination With Fulvestrant

Arm 2, Part 1 - Mirdametinib as Single Agent

Arm 2, Part 2 - Mirdametinib as Single Agent

Arm 1, Part 2 - Mirdametinib in Combination With Fulvestrant

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

5Treatment groups

Experimental Treatment

Group I: Phase I: Recurrent and/or progressive low-grade glioma without prior exposure to MEK inhibitorsExperimental Treatment1 Intervention

Participants will receive mirdametinib at one of the dose levels twice daily days 1-28. For the first cycle of treatment, participants will take mirdametinib tablets dissolved in water. After the first cycle of treatment, participants may receive the medicine the same way (dissolved in water) or may receive capsules. Treatment repeats every 28 days for up to 26 cycles of treatment (24 months) in the absence of disease progression or unacceptable toxicity.

Group II: Phase 2, Cohort 3b:Experimental Treatment1 Intervention

Participants with recurrent and/or progressive low-grade glioma who previously received ≥ 6 courses MEK inhibitor (including mirdametinib) and did not progress while on active MEKi therapy. Participants will receive the RP2D of mirdametinib. Participants may take mirdametinib tablets dissolved in water, or receive capsules. Therapy will be administered in cycles of 28 days and may be continued for up to 24 months (26 cycles) in absence of disease progression or unacceptable toxicity.

Group III: Phase 2, Cohort 3a:Experimental Treatment1 Intervention

Participants with recurrent and/or progressive low-grade glioma who previously received ≥ 6 courses MEK inhibitor (including mirdametinib) and did not progress while on active MEKi therapy. Participants will receive the RP2D of mirdametinib. Participants with previous exposure to mirdametinib may receive a starting dose lower than the RP2D, depending on the dose they tolerated during their previous exposure. Participants may take mirdametinib tablets dissolved in water, or receive capsules. Therapy will be administered in cycles of 28 days and may be continued for up to 24 months (26 cycles) in absence of disease progression or unacceptable toxicity.

Group IV: Phase 2, Cohort 2: Recurrent and/or Progressive without prior exposure to MEK inhibitorsExperimental Treatment1 Intervention

Participants will receive the RP2D of mirdametinib. Participants may take mirdametinib tablets dissolved in water, or receive capsules. Therapy will be administered in cycles of 28 days and may be continued for up to 24 months (26 cycles) in absence of disease progression or unacceptable toxicity.

Group V: Phase 2, Cohort 1: Newly diagnosed and/or previously untreated (except surgery)Experimental Treatment1 Intervention

Participants will receive the RP2D of mirdametinib. Therapy will be administered in cycles of 28 days and may be continued for up to 24 months (26 cycles) in absence of disease progression or unacceptable toxicity.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

PD-0325901

Not yet FDA approved

0 / 16Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Low Grade Glioma (LGG) include MEK inhibitors like mirdametinib, which target the MAPK/ERK pathway to reduce tumor growth by inhibiting cell proliferation and survival signals. Temozolomide, an alkylating agent, works by damaging the DNA of cancer cells, leading to cell death. Radiation therapy induces DNA damage to kill cancer cells and shrink tumors. These treatments are significant for LGG patients as they specifically target the molecular and cellular mechanisms driving tumor growth, potentially leading to better control of the disease and improved patient outcomes.