Selumetinib for Neurofibromatosis

Not currently recruiting at 1 trial location

Overseen By Brigitte C Widemann, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Investigational agents, MEK inhibitors

Disqualifiers: Pregnancy, Uncontrolled illness, Cardiac disorder, Ophthalmologic 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: Up to 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the drug selumetinib to determine if it can shrink or slow the growth of plexiform neurofibromas (PNs), nerve tumors caused by neurofibromatosis type 1 (NF1). Currently, no effective treatments exist for PNs, especially when they are too large or located in difficult areas for surgical removal. Participants will take selumetinib capsules twice daily, and researchers will monitor the drug's impact on symptoms and how the body processes it. The trial seeks individuals 18 and older with NF1 who have inoperable PNs that cause health issues or are growing. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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

The trial protocol does not specify if you need to stop taking your current medications. However, it advises avoiding medications that affect certain liver enzymes, as they might interfere with the study drug. It's best to discuss your current medications with the trial team.

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

Research has shown that selumetinib has been tested for its effects on tumors in people with neurofibromatosis type 1 (NF1). In earlier studies, selumetinib significantly reduced tumor size in many patients and helped decrease pain and the need for pain medication.

Regarding safety, selumetinib was generally well-tolerated. Some side effects, such as diarrhea and skin rashes, were reported but usually manageable. Notably, the FDA has already approved selumetinib for use in children with NF1 and tumors that cannot be surgically removed, supporting its safe use.

Overall, while side effects can occur, existing research supports the safety of selumetinib in treating tumors related to NF1. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Selumetinib is unique because it targets the MEK pathway, which is an essential part of the cell signaling process involved in the growth of neurofibromas in Neurofibromatosis. Unlike traditional treatments like surgery or radiotherapy, which focus on removing or shrinking tumors, selumetinib works at the molecular level to prevent tumor growth from the inside out. Researchers are excited about selumetinib because it offers a non-invasive option that directly interferes with the biological mechanisms fueling the condition, potentially leading to more effective and less intrusive management of Neurofibromatosis.

What evidence suggests that selumetinib might be an effective treatment for neurofibromatosis?

Research has shown that selumetinib can help shrink plexiform neurofibromas (PNs) in individuals with neurofibromatosis type 1 (NF1). Studies have found that selumetinib reduces tumor size, with noticeable effects beginning about 7 months after treatment starts. Reports also indicate less pain and a reduced need for pain medication in patients taking selumetinib. These findings suggest that selumetinib could be a promising treatment for PNs that are difficult to operate on. Selumetinib is already known to be safe and effective for some children with NF1, and similar benefits are expected for adults. ^{1 2 6 7 8}

Who Is on the Research Team?

Brigitte C Widemann, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

Adults over 18 with Neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PNs), which are tumors along nerves causing health issues or growing. Participants must not be on other investigational drugs, have certain NF1-related tumors needing treatment, uncontrolled illnesses, or be pregnant/breastfeeding without contraception. They should be able to swallow capsules and undergo MRI scans.

Inclusion Criteria

My tumor cannot be removed by surgery and is causing or could cause health problems.

I am willing to have needle biopsies of my tumor before and during treatment.

I can undergo multiple MRI scans for monitoring.

Exclusion Criteria

I have NF1 and need treatment with chemo or surgery.

I do not have any uncontrolled illnesses like heart failure or active infections.

Patients who are receiving any other investigational agents, or have received an investigational agent within the past 30 days

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive selumetinib capsules every 12 hours for several 28-day cycles

Up to 24 months

Several visits throughout the study

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Final visit after stopping selumetinib

Extension

Participants with non-progressive, symptomatic PN at enrollment may continue treatment until progression of disease

Until progression of disease

What Are the Treatments Tested in This Trial?

Interventions

• Selumetinib

Trial Overview

The trial is testing Selumetinib's effectiveness on shrinking or slowing the growth of PNs in NF1 patients. It involves taking Selumetinib capsules twice daily for multiple 28-day cycles, as long as it's tolerated and the disease doesn't progress. The study includes regular visits for medical tests to monitor effects.

How Is the Trial Designed?

Group I: 1 Experimental Treatment 1 Intervention

Selumetinib 50 mg BID daily

Selumetinib is already approved in United States, European Union for the following indications:

Approved in United States as Koselugo for:

• Neurofibromatosis type 1 (NF1) in pediatric patients 2 years of age and older with symptomatic, inoperable plexiform neurofibromas (PN)

Approved in European Union as Koselugo for:

• Neurofibromatosis type 1 (NF1) in pediatric patients 2 years of age and older with symptomatic, inoperable plexiform neurofibromas (PN)

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

A Phase I study involving 24 healthy male volunteers evaluated a new granule formulation of selumetinib, showing that its absorption is comparable to the existing capsule form, making it a potential alternative for younger patients or those who have difficulty swallowing capsules.

The study found that the granule formulation was well-tolerated with low incidence of mild adverse events, and participants rated its palatability positively, indicating they would be willing to take it again.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase I, Open-label, Randomized, Crossover Study of the Relative Bioavailability of Capsule and Granule Formulations of Selumetinib. Cohen-Rabbie, S., Mattinson, A., So, K., et al.[2022]

Selumetinib (KOSELUGO) was approved by the FDA for treating pediatric patients aged 2 and older with inoperable plexiform neurofibromas, showing a 66% overall response rate in a trial of 50 patients, with many experiencing significant symptom relief for at least 12 months.

While selumetinib is effective, it carries risks typical of MEK inhibitors, including potential ocular, cardiac, and gastrointestinal side effects, but the overall benefit-risk assessment is considered favorable for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Selumetinib for Plexiform Neurofibroma. Casey, D., Demko, S., Sinha, A., et al.[2022]

Selumetinib, a MEK inhibitor, has shown significant efficacy in treating plexiform neurofibromas in patients with neurofibromatosis type 1, with 68% of 50 symptomatic patients experiencing a partial response and a median tumor volume reduction of 27.9%.

The treatment demonstrated a favorable safety profile, with manageable adverse effects, and resulted in an 84% estimated progression-free survival at 3 years, marking it as the first FDA-approved therapy for inoperable plexiform neurofibromas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Review of Selumetinib in the Treatment of Neurofibromatosis Type 1-Related Plexiform Neurofibromas. Anderson, MK., Johnson, M., Thornburg, L., et al.[2022]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40473450/

Efficacy and safety of selumetinib in adults with ... - PubMed

The observations of reduction in tumour volume by cycle 16, reduction in chronic and spike pain, reduction in analgesia, and decrease in pain ...

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.

koselugohcp.com

koselugohcp.com/efficacy

Koselugo® (selumetinib) | Efficacy

Evident response with a median time to onset of 7.2 months in patients with NF1 PN · Estimated DOR based on SPRINT data using the Kaplan-Meier method · Median ...

4.

merck.com

merck.com/news/koselugo-selumetinib-showed-significant-and-clinically-meaningful-improvement-in-objective-response-rate-versus-placebo-in-adults-with-neurofibromatosis-type-1-who-have-symptomatic-inoperable/

KOSELUGO® (selumetinib) Showed Significant and ...

These results showed reduction in tumor volume, building on the established safety and efficacy profile of KOSELUGO in certain children.

5.

astrazeneca.com

astrazeneca.com/media-centre/press-releases/2024/komet-phase-iii-trial-met-primary-endpoint.html

Koselugo showed statistically significant and clinically ...

Results demonstrated reduction in tumour volume, building on established safety and efficacy profile of Koselugo in children and supporting expanded use in ...

6.

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 ...

7.

fda.gov

fda.gov/drugs/resources-information-approved-drugs/fda-approves-selumetinib-pediatric-patients-1-year-age-and-older-neurofibromatosis-type-1

FDA approves selumetinib for pediatric patients 1 year of ...

FDA approves selumetinib for pediatric patients 1 year of age and older with neurofibromatosis type 1 with symptomatic, inoperable plexiform ...

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) ...