MEK Inhibitor Mirdametinib (PD-0325901) in Patients With Neurofibromatosis Type 1 Associated Plexiform Neurofibromas

NCT ID: NCT03962543

Last Updated: 2025-08-07

Study Results

Results available

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Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

114 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-09-29

Study Completion Date

2028-12-22

Brief Summary

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This study evaluates mirdametinib (PD-0325901) in the treatment of symptomatic inoperable neurofibromatosis type-1 (NF1)-associated plexiform neurofibromas (PNs). All participants will receive mirdametinib (PD-0325901). Eligible participants may continue in a long-term follow-up phase.

Detailed Description

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Neurofibromas are non-malignant peripheral nerve sheath tumors, which are classified as plexiform neurofibromas (PNs) if they extend longitudinally along a nerve and involve multiple fascicles. PNs are a major cause of morbidity and disfigurement in individuals with NF1, and as the tumor growth progresses, can cause a multitude of clinical problems including pain and impaired physical function. PNs have the potential to undergo malignant transformation to Malignant Peripheral Nerve Sheet Tumors (MPNST).

Mirdametinib (PD-0325901) is an orally delivered, highly selective small-molecule inhibitor of the dual specificity kinases, MEK1 and MEK2 (MAPK/ERK Kinase) which prevents the phosphorylation and subsequent activation of mitogen-activated protein kinase (MAPK).

Previous studies of mirdametinib (PD-0325901) demonstrated PN shrinkage and sustained inhibition of pERK. Reduced tumor volume indicated that cell proliferation or cell death may be altered in PNs with administration of mirdametinib (PD-0325901).

Conditions

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Plexiform Neurofibroma Neurofibromatosis Type 1 (NF1)

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

All participants will receive mirdametinib (PD-0325901) at a dose of 2 mg/m\^2 twice daily (maximum dose of 4 mg twice daily), calculated based on body surface area. Dose will be administered in a 3-week on, 1-week off schedule.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Mirdametinib (PD-0325901)

Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily

Group Type EXPERIMENTAL

Mirdametinib (PD-0325901) oral capsule or dispersible tablet

Intervention Type DRUG

Mirdametinib (PD-0325901) capsule or dispersible tablet

Interventions

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Mirdametinib (PD-0325901) oral capsule or dispersible tablet

Mirdametinib (PD-0325901) capsule or dispersible tablet

Intervention Type DRUG

Other Intervention Names

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PD-0325901 Mirdametinib

Eligibility Criteria

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Inclusion Criteria

* Participant has documented NF1 mutation or a diagnosis of neurofibromatosis type 1 (NF1) using National Institute of Health (NIH) Consensus Conference criteria inclusive of the presence of a plexiform neurofibroma (PN).
* Participant has a PN that is causing significant morbidity.
* Participant has a PN that cannot be completely surgically removed.
* Participant has a target tumor that is amenable to volumetric MRI analysis.
* Participant is willing to undergo a tumor biopsy pre and post treatment if ≥ 18 years of age.
* Participant has adequate organ and bone marrow function.

Exclusion Criteria

* Participant has abnormal liver function or history of liver disease.
* Participant has lymphoma, leukemia or any malignancy within the past 5 years (except for resected basal/squamous skin carcinomas without metastases within 3 years).
* Participant has breast cancer within 10 years.
* Participant has active optic glioma or other low-grade glioma requiring treatment.
* Participant has abnormal QT interval corrected or other heart disease within 6 months.
* Participant has a history of retinal pathology, risk factors for retinal vein occlusion or has a history of glaucoma.
* Participant has known malabsorption syndrome or gastrointestinal conditions that would impair absorption of mirdametinib (PD-0325901).
* Participant has received NF1 PN-targeted therapy within 45 days.
* Participant previously received or is currently receiving therapy with mirdametinib (PD-0325901) or any other MEK1/2 inhibitor.
* Participant has received radiation therapy within 6 months or has received radiation to the orbit at any time.
* Participant is unable to undergo or tolerate MRI.
* Participant has active bacterial, fungal or viral infection.
* Participant has experienced other severe acute or chronic medical or psychiatric conditions within 1 year.
Minimum Eligible Age

2 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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SpringWorks Therapeutics, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Christopher L Moertel, MD

Role: PRINCIPAL_INVESTIGATOR

University of Minnesota

Locations

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University of Alabama at Birmingham/Children's of Alabama

Birmingham, Alabama, United States

Site Status

Mayo Clinic Hospital

Phoenix, Arizona, United States

Site Status

Arkansas Children's Hospital

Little Rock, Arkansas, United States

Site Status

Children's Hospital Los Angeles

Los Angeles, California, United States

Site Status

UCLA Oncology Center

Los Angeles, California, United States

Site Status

University of California - Irvine Health

Orange, California, United States

Site Status

Children's Hospital of Orange County

Orange, California, United States

Site Status

Lucile Packard Children's Hospital Stanford

Palo Alto, California, United States

Site Status

University of California - Davis Comprehensive Cancer Center

Sacramento, California, United States

Site Status

Children's Hospital Colorado

Aurora, Colorado, United States

Site Status

Nemours A. I. duPont Hospital for Children

Wilmington, Delaware, United States

Site Status

Children's National Medical Center

Washington D.C., District of Columbia, United States

Site Status

University of Florida Clinical Research Center

Gainesville, Florida, United States

Site Status

Nicklaus Children's Hospital

Miami, Florida, United States

Site Status

AdventHealth Pediatric Oncology Hematology at Orlando

Orlando, Florida, United States

Site Status

Orlando Health, Inc.

Orlando, Florida, United States

Site Status

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, United States

Site Status

Moffitt Cancer Center

Tampa, Florida, United States

Site Status

Children's Healthcare of Atlanta - Center for Advanced Pediatrics

Atlanta, Georgia, United States

Site Status

University of Illinois Hospital and Health Systems

Chicago, Illinois, United States

Site Status

University of Chicago Medical Centers

Chicago, Illinois, United States

Site Status

IU Health Brain Tumor Infusion Clinic

Indianapolis, Indiana, United States

Site Status

University of Iowa Hospitals & Clinics

Iowa City, Iowa, United States

Site Status

Kosair Charities Pediatric Clinical Research Unit

Louisville, Kentucky, United States

Site Status

University of Michigan CS Mott Children's Hospital

Ann Arbor, Michigan, United States

Site Status

Henry Ford Hospital

Detroit, Michigan, United States

Site Status

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Washington University School of Medicine-Siteman Cancer Center

St Louis, Missouri, United States

Site Status

St. Joseph's Univeristy Medical Center

Paterson, New Jersey, United States

Site Status

Albany Medical Center

Albany, New York, United States

Site Status

Children's Hospital at Montefiore

The Bronx, New York, United States

Site Status

UNC Medical Center

Chapel Hill, North Carolina, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

University of Cincinnati Medical Center

Cincinnati, Ohio, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status

University of Oklahoma Health Sciences Center, Jimmy Everest Center for Cancer and Blood Disorders in Children

Oklahoma City, Oklahoma, United States

Site Status

Oregon Health and Science University

Portland, Oregon, United States

Site Status

Children's Hospital of Pittsburgh UPMC

Pittsburgh, Pennsylvania, United States

Site Status

Henry-Joyce Cancer Clinic

Nashville, Tennessee, United States

Site Status

Children's Medical Center

Dallas, Texas, United States

Site Status

Cook Children's Medical Center

Fort Worth, Texas, United States

Site Status

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status

University of Utah, Center for Clinical and Translational Sciences

Salt Lake City, Utah, United States

Site Status

UVA Health, Division of Neuro-Oncology

Charlottesville, Virginia, United States

Site Status

Children's Hospital of The King's Daughters

Norfolk, Virginia, United States

Site Status

Swedish Medical Center - Cherry Hill Campus

Seattle, Washington, United States

Site Status

MACC Fund Research Center

Milwaukee, Wisconsin, United States

Site Status

Countries

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United States

References

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Moertel CL, Hirbe AC, Shuhaiber HH, Bielamowicz K, Sidhu A, Viskochil D, Weber MD, Lokku A, Smith LM, Foreman NK, Hajjar FM, McNall-Knapp RY, Weintraub L, Antony R, Franson AT, Meade J, Schiff D, Walbert T, Ambady P, Bota DA, Campen CJ, Kaur G, Klesse LJ, Maraka S, Moots PL, Nevel K, Bornhorst M, Aguilar-Bonilla A, Chagnon S, Dalvi N, Gupta P, Khatib Z, Metrock LK, Nghiemphu PL, Roberts RD, Robison NJ, Sadighi Z, Stapleton S, Babovic-Vuksanovic D, Gershon TR; ReNeu Trial Investigators; ReNeu Study Investigators. ReNeu: A Pivotal, Phase IIb Trial of Mirdametinib in Adults and Children With Symptomatic Neurofibromatosis Type 1-Associated Plexiform Neurofibroma. J Clin Oncol. 2025 Feb 20;43(6):716-729. doi: 10.1200/JCO.24.01034. Epub 2024 Nov 8.

Reference Type DERIVED
PMID: 39514826 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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MEK-NF-201

Identifier Type: -

Identifier Source: org_study_id

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