MEK 1/2 Inhibitor Selumetinib (AZD6244 Hydrogen Sulfate) in Adults With Neurofibromatosis Type 1 (NF1) and Inoperable Plexiform Neurofibromas

Running, not enrolling · Phase 2

Conditions studied: Neurofibromatosis 1 (NF1), Plexiform Neurofibromas (PN)

In brief

Background: Neurofibromatosis type 1 (NF1) is a disorder that can cause plexiform neurofibromas (PNs). These are tumors that grow along nerves. Some PNs cause serious health problems. PNs often can t be operated on because of their large size, location, or number. There are no effective treatments known for people with NF1 and PNs. Researchers want to test if the drug selumetinib (AZD6244 hydrogen sulfate) causes PNs to shrink or slows down their growth. Objectives: To test if selumetinib helps treat PNs. To test how the body handles selumetinib and how it affects peoples symptoms. Eligibility: People ages 18 and older with NF1, with an inoperable PN that causes morbidity or is growing Design: Participants will be screened with: Medical history and physical exam Blood, urine, and heart tests Eye exam MRI: They lie in a machine that takes pictures of the body. PN biopsy: A small piece of the tumor is removed by a large needle. Questionnaires Participants will swallow selumetinib capsules every 12 hours for several 28-day cycles. The capsules are taken with a full glass of water on an empty stomach. Participants may have only water for 2 hours before and 1 hour after each dose. Participants will keep a drug diary. They will continue taking the drug as long as they tolerate it and their disease doesn t progress. Participants will have several visits throughout the study. These will include repeats of the screening tests. Participants will have a final visit after they stop taking selumetinib. ...

Key facts

Study ID

NCT02407405

Run by

National Cancer Institute (NCI)

People needed

36

Starts

2016-01-07

Expected to finish

2030-01-01

Last updated by the study team

2026-08-07

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

• Patients who are receiving any other investigational agents, or have received an investigational agent within the past 30 days.
• May not have a NF1 related tumor such as optic pathway glioma or malignant peripheral nerve sheath tumor, which requires treatment with chemotherapy or surgery.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, active bleeding diatheses or renal transplant, including any patient known to have hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements. Patients with HIV who have adequate CD4 counts and who have no requirement for antiviral therapy will be eligible.
• Pregnant or breast-feeding females are excluded due to potential risks of fetal and teratogenic adverse events of an investigational agent. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method. Abstinence is an acceptable method of birth control.
• Prior treatment with selumetinib or another specific MEK 1/2 inhibitor.
• Supplementation with vitamin E greater than 100% of the daily recommended dose.
• Inability to swallow capsules, since capsules cannot be crushed or broken.
• Inability to undergo MRI and/or contraindication for MRI examinations following the MRI protocol. Prosthesis or orthopedic or dental braces that would interfere with volumetric analysis of target PN on MRI.
• Refractory nausea and vomiting, chronic gastrointestinal diseases (e.g., inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption.
• Uncontrolled hypertension (despite medical therapy); blood pressure should be <140/90 in accordance with American Heart Association definition of hypertension.
• While not an exclusion criterion, unless clinically indicated, patients should avoid taking other additional non-study medications that may interfere with the study medications. In particular, patients should avoid medications that are known to either induce or inhibit the activity of hepatic microsomal isoenzymes CYP1A2, CYP2C19 and CYP3A4, as this may interfere with the metabolism of selumetinib.
• Known Cardiac Disorder, including:
• Known inherited coronary disease
• Symptomatic heart failure (NYHA Class II-IV prior or current cardiomyopathy, or severe valvular heart disease)
• Current cardiomyopathy
• Severe valvular heart disease
• Atrial fibrillation
• Ejection fraction (ECHO) <53%
• QTcF >450 msec
• Known Ophthalmologic conditions, such as:
• Current or past history of central serous retinopathy
• Current or past history of retinal vein occlusion
• Known intraocular pressure (IOP) > 21 mmHg (or ULN adjusted by age) or uncontrolled glaucoma (irrespective of IOP). Patients with known glaucoma and increased IOP who do not have meaningful vision (light perception only or no light perception) and are not experiencing pain related to the glaucoma, may be eligible after discussion with the study chair.
• Subjects with any other significant abnormality on ophthalmic examination should be discussed with the Study Chair for potential eligibility
• Ophthalmological findings secondary to long-standing optic pathway glioma (such as visual loss, optic nerve pallor or strabismus) or long-standing orbito-temporal PN (such as visual loss, strabismus) will NOT be considered a significant abnormality for the purposes of the study

Where it is running

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States

Full record on ClinicalTrials.gov

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