Selumetinib for Plexiform Neurofibroma

Not currently recruiting at 11 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: < 18

Sex: Any

Trial Phase: Phase 1

Sponsor: AstraZeneca

Must not be taking: Vitamin E

Disqualifiers: Cancer, Cardiovascular disease, Liver, others

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

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: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effects of selumetinib, a medication, on treating plexiform neurofibromas (PN) in teenagers with neurofibromatosis type 1 (NF1), a genetic condition that causes non-cancerous tumors to grow on nerve tissue. Researchers aim to assess how a low-fat meal affects the drug’s absorption and its impact on stomach-related side effects when taken with or without food. This study may help determine the best way to take selumetinib while maintaining its effectiveness and safety. It seeks participants aged 12 to 18 with NF1 and PN that cannot be surgically removed and who require treatment due to symptoms or potential complications. As a Phase 1 trial, the research focuses on understanding how the treatment works in people.

Will I have to stop taking my current medications?

The trial requires that any multivitamin containing vitamin E must be stopped at least 7 days before starting selumetinib. The protocol does not specify other medication restrictions, so it's best to discuss your current medications with the study team.

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

Research has shown that selumetinib is generally well-tolerated in children with neurofibromatosis type 1 (NF1) and tumors that cannot be surgically removed. Studies indicate that long-term use can help shrink tumors and relieve pain. However, some patients experienced side effects, such as vomiting, diarrhea, nausea, and skin rashes, which sometimes required dosage adjustments. Importantly, the FDA has already approved selumetinib for treating NF1 in children, suggesting it is considered safe for this use. Overall, while side effects can occur, selumetinib has proven effective with a manageable safety profile. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about selumetinib for plexiform neurofibroma because it targets a specific pathway in the cells that current treatments don't. Unlike standard options like surgery or radiation, which can be invasive or have significant side effects, selumetinib is an oral medication that inhibits the MEK enzyme. This enzyme is part of a pathway known to promote tumor growth in neurofibromatosis type 1. By targeting this pathway, selumetinib has the potential to shrink these problematic tumors and improve quality of life for patients with fewer side effects.

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

Research has shown that selumetinib holds promise for treating plexiform neurofibromas (PN) that cannot be surgically removed in patients with neurofibromatosis type 1 (NF1). Studies have found that selumetinib can significantly shrink these tumors, which is crucial for managing the condition. In earlier trials, patients reported less chronic and sudden pain from these tumors. The treatment was well-tolerated, with no new safety issues identified. Overall, selumetinib has effectively reduced tumor size and improved the quality of life for people with NF1-related PN. Participants in this trial will receive selumetinib in a single treatment arm to further evaluate its effectiveness and safety. ^{3 6 7 8 9}

Who Is on the Research Team?

Study physician Study physician, MD

Principal Investigator

AstraZeneca

Are You a Good Fit for This Trial?

Adolescents aged 12-17 with Neurofibromatosis Type 1 (NF1) and inoperable Plexiform Neurofibromas (PN), who have symptoms or risk of complications. They must not have had recent major surgery, abnormal eye conditions, significant heart disease, poor liver or kidney function, previous MEKi treatment issues, unresolved toxicity from past treatments for NF1-PN, or any life-threatening illness.

Inclusion Criteria

I need treatment for NF1 and inoperable PN due to symptoms or risk of serious complications.

I am between 12 and 17 years old.

My body surface area is between 1.3 and 2.5 square meters.

Exclusion Criteria

I stopped or lowered my MEKi treatment due to side effects.

Participants with abnormal ophthalmological findings/conditions as listed in the protocol

I have no active cancer treatments, except for certain skin cancers or cancers I've been free from for 2+ years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

Up to 4 weeks

Treatment Period 1

Participants receive selumetinib 25 mg/m2 bid in a fed state for 28 days

4 weeks

Cycle 1 Day 8 visit for PK sampling

Washout

A 7-day washout period between treatment periods

1 week

Treatment Period 2

Participants receive selumetinib 25 mg/m2 bid in a fasted state for 28 days

4 weeks

Cycle 1 Day 8 visit for PK sampling

Extension to Treatment Period 2

Continuation of treatment until results from the primary analysis are available

Treatment Period 3 (if required)

Participants receive an adjusted dose of selumetinib in a fed state for 3 cycles

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Selumetinib

Trial Overview The trial is testing the drug Selumetinib to see how taking it with a low-fat meal affects its absorption and gastrointestinal side effects in young patients. The goal is to find an effective dose that can be taken with food while maintaining safety and efficacy.

How Is the Trial Designed?

Group I: selumetinib single arm Experimental Treatment 1 Intervention

This is a sequential study consisting of a screening period lasting up to 28 days, a 28 day (1 cycle) treatment period (T1) in a fed state, a 7 day washout period, a further 1 cycle treatment period (T2) in a fasted state and an extension to T2 until results from the primary analysis are available. During Treatment Period 1 and 2 all participants will receive selumetinib (25 mg/m2 bid). If a third treatment period (T3) is required, participants will enter a 7 day washout period followed by a treatment period in a fed state at an adjusted dose for 3 cycles.

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?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

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

Efficacy and safety of selumetinib in adults with ... Data from the primary analysis of KOMET indicate that selumetinib treatment achieved a significant objective response rate versus placebo by ...

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

Efficacy and safety of selumetinib in adults with ... - PubMed No new safety concerns were identified. The observations of reduction in tumour volume by cycle 16, reduction in chronic and spike pain, ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04924608

NCT04924608 | Efficacy and Safety of Selumetinib in ... A global study to demonstrate the effectiveness of selumetinib in participants with NF1 who have symptomatic, inoperable plexiform neurofibromas. Detailed ...

4. koselugohcp.com koselugohcp.com/efficacy

Koselugo® (selumetinib) | Efficacy Long-term safety and efficacy of selumetinib in children with neurofibromatosis type 1 on a phase 1/2 trial for inoperable plexiform neurofibromas. Neuro ...

5. 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.

6. koselugohcp.com koselugohcp.com/safety

Koselugo® (selumetinib) | Safety Adverse reactions requiring a dosage interruption or reduction in ≥5% of patients were vomiting, paronychia, diarrhea, nausea, abdominal pain, rash, skin ...

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. 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.

9. clinicaltrials.gov clinicaltrials.gov/study/NCT04924608

NCT04924608 | Efficacy and Safety of Selumetinib in ... A global study to demonstrate the effectiveness of selumetinib in participants with NF1 who have symptomatic, inoperable plexiform neurofibromas.