Selumetinib for Plexiform Neurofibroma

(NF114 Trial)

Recruiting at 9 trial locations

Overseen By Juliette Southworth, BS

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Alabama at Birmingham

Must be taking: Antihypertensives

Must not be taking: Chemotherapy, Immunotherapy, Biologic therapy, others

Disqualifiers: Cancer, Severe disease, Cardiac conditions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether early treatment with selumetinib, a type of medication, can benefit young children with NF1 who have plexiform neurofibromas (PN) in challenging locations before they cause problems. Selumetinib has been shown to shrink these tumors in children, potentially alleviating symptoms like pain or movement issues. The study targets children with NF1 who either do not have any known PNs yet or have them in high-risk areas without symptoms. Participants should not have previously undergone an MRI for these tumors or received selumetinib treatment. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications to join the trial?

The trial requires stopping any herbal supplements or medications that affect certain liver enzymes at least 14 days before starting the study medication. If you are on blood pressure medication, you must be on a stable regimen for at least 30 days before joining. Other medications are not specifically mentioned, so it's best to discuss with the study team.

Is there any evidence suggesting that selumetinib is likely to be safe for humans?

Research has shown that selumetinib has been well-studied in children with neurofibromatosis type 1 (NF1) who have plexiform neurofibromas (PN) that cannot be surgically removed. In a previous study with 74 children, selumetinib was generally well-tolerated. Most children experienced lasting tumor shrinkage, meaning the tumors became smaller and remained so. Many also reported less pain after taking the drug.

Common side effects included nausea, vomiting, and diarrhea, but these were generally manageable. Another study demonstrated that with up to five years of treatment, children continued to do well with selumetinib, experiencing ongoing tumor shrinkage and pain relief. This long-term data suggests that selumetinib's safety remains consistent over time.

In summary, selumetinib has shown a reliable safety record in children with NF1-related PN, providing both tumor reduction and pain relief with manageable side effects. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for plexiform neurofibroma?

Most treatments for plexiform neurofibromas, which often include surgery or watchful waiting, focus on managing symptoms rather than directly targeting the root cause. Selumetinib is unique because it specifically targets the MEK pathway, which plays a key role in the growth of these tumors. This targeted approach holds promise for actually slowing or stopping tumor growth, rather than just alleviating symptoms. Researchers are excited about Selumetinib because it offers a potential non-surgical option for managing these challenging tumors, particularly in young patients with high-risk tumors.

What is the effectiveness track record for selumetinib in treating plexiform neurofibroma?

Research has shown that selumetinib effectively treats plexiform neurofibromas (PN) in children with neurofibromatosis type 1 (NF1). In previous studies, most children experienced significant tumor shrinkage, which improved symptoms like pain and movement. The SPRINT study found that selumetinib was effective in 68% of cases, reducing tumor size for most participants. Even in adults, selumetinib decreased tumor size and relieved pain. In this trial, participants will be randomized to receive selumetinib or undergo observation to assess its effectiveness in preventing PN growth. These findings suggest that selumetinib could be a promising treatment for PN in both children and adults. ^{3 5 6 7 8}

Are You a Good Fit for This Trial?

This trial is for children aged over 1 year but under 8 with Neurofibromatosis Type 1 (NF1) who have Plexiform Neurofibromas (PN) in high-risk areas but don't yet show symptoms. They must not have had previous MRIs of the PN area and should be generally healthy based on a recent physical exam.

Inclusion Criteria

You do not have a known peripheral neuropathy before joining the study. If there is a suspicion of peripheral neuropathy, you may still join the study if the study chair agrees, and you have not had an MRI of the area in question and are not showing any other symptoms.

You had a physical exam at your doctor's office within the last year before giving your agreement to participate.

I am between 1 and 8 years old.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Part 1: WBMRI for NF1 patients

To assess the incidence of asymptomatic PN in any location in participants with NF1 and no known PN

Varies

Part 2: Treatment randomization

Randomization to selumetinib vs observation to determine if selumetinib prevents PN growth in young participants with asymptomatic tumors

60 months

Part 3: Intermittent dosing schedule

To assess the proportion of participants who are able to maintain tumor response after transition to an intermittent dosing schedule

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Selumetinib

Trial Overview The study tests if early treatment with Selumetinib can prevent growth or complications from asymptomatic PNs in NF1 patients. It's based on prior success where Selumetinib shrank PNs, improving pain and mobility in children.

How Is the Trial Designed?

Group I: Part 3: Part 2 participants with growing or symptomatic PN Experimental Treatment 1 Intervention

To assess the proportion of participants who are able to maintain tumor response after transition to an intermittent dosing schedule

Group II: Part 2: Treatment randomization to selumetinib vs observation Experimental Treatment 1 Intervention

To determine if selumetinib treatment prevents PN growth in young participants with asymptomatic tumors in high-risk locations

Group III: Part 1: WBMRI for NF1 patients with no known PN Active Control 1 Intervention

To assess the incidence of asymptomatic PN in any location in participants with NF1 and no known PN

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Children's Hospital of Philadelphia

Collaborator

Trials

749

Recruited

11,400,000+

Congressionally Directed Medical Research Programs

Collaborator

Trials

59

Recruited

10,600+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12298819/

Selumetinib in Adult Neurofibromatosis 1 with Plexiform ... Results: We present a case of a 38-year-old male with a right facial PN successfully treated with selumetinib, resulting in a 16.77% tumor ...

2. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(25)00986-9/fulltext?rss=yes

Efficacy and safety of selumetinib in adults with ... The observations of reduction in tumour volume by cycle 16, reduction in chronic and spike pain, reduction in analgesia, and decrease in pain ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1912735

Selumetinib in Children with Inoperable Plexiform ... In this phase 2 trial, most children with neurofibromatosis type 1 and inoperable plexiform neurofibromas had durable tumor shrinkage and clinical benefit from ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0140673625009869

Efficacy and safety of selumetinib in adults with ... These approvals were based on the pivotal SPRINT study, in which selumetinib showed an overall response rate of 68% and provided a clinically meaningful ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38975694/

Safety and efficacy of selumetinib in pediatric and adult ... Selumetinib decreases PN volume in the majority of pediatric and adult NF1 patients while also showing efficacy in nonmalignant diverse NF1 manifestations.

6. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-approves-selumetinib-neurofibromatosis-type-1-symptomatic-inoperable-plexiform-neurofibromas

FDA approves selumetinib for neurofibromatosis type 1 ... The primary safety data were from 74 pediatric patients with NF1 and PN who received selumetinib during SPRINT. The most common adverse ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37115514/

Long-term safety and efficacy of selumetinib in children with ... With up to 5 years of additional selumetinib treatment, most children with NF1-related PN had durable tumor shrinkage and sustained improvement in pain.

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.3014

Efficacy and safety of selumetinib in adults with ... Conclusions: In the first international, randomized, placebo-controlled trial in adults with NF1-PN, SELU achieved a significant ORR vs PBO (C16) ...