Selumetinib for Plexiform Neurofibroma

Recruiting at 8 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

24 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing how well selumetinib works when taken with a low-fat meal in adolescents with NF1 who have tumors that can't be removed by surgery. The goal is to see if eating a low-fat meal affects how the body absorbs the medication and if it helps reduce stomach-related side effects. Selumetinib is being investigated for its effectiveness in treating NF1-associated tumors, with previous studies showing promising positive results in patients.

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.

What data supports the effectiveness of the drug Selumetinib for treating plexiform neurofibromas?

Selumetinib has been shown to be effective in treating plexiform neurofibromas in children with neurofibromatosis type 1, with a 66% response rate in a clinical trial. Many patients experienced improvements in symptoms and functional impairments, and the benefits were considered to outweigh the risks. ^{1 2 3 4 5}

Is Selumetinib safe for humans?

Selumetinib has been evaluated for safety in both children and adults, showing risks consistent with its drug class, including potential eye, heart, muscle, stomach, and skin issues. Safety data from trials in pediatric patients with plexiform neurofibromas and other cancer indications support its use, with a favorable benefit-risk assessment. ^{2 3 4 5 6}

How is the drug Selumetinib unique for treating plexiform neurofibroma?

Selumetinib is unique because it is an oral medication specifically approved for children with neurofibromatosis type 1 who have symptomatic, inoperable plexiform neurofibromas, and it works by inhibiting the MEK1/2 enzymes, which are part of a pathway involved in tumor growth. Unlike other treatments, it has shown a significant response rate in reducing tumor size and improving symptoms in clinical trials. ^{1 2 3 4 5}

Research Team

Study physician Study physician, MD

Principal Investigator

AstraZeneca

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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, 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Selumetinib for plexiform neurofibromas in neurofibromatosis type 1: a single-institution experience. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Selumetinib for Plexiform Neurofibroma. [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Selumetinib: First Approval. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

A Phase I, Open-label, Randomized, Crossover Study of the Relative Bioavailability of Capsule and Granule Formulations of Selumetinib. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Selumetinib in Japanese pediatric patients with neurofibromatosis type 1 and symptomatic, inoperable plexiform neurofibromas: An open-label, phase I study. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

A Review of Selumetinib in the Treatment of Neurofibromatosis Type 1-Related Plexiform Neurofibromas. [2022]