What is the mechanism of action of this treatment?

MEK inhibitors, such as selumetinib, work by blocking the MEK enzyme, which is part of the MAPK/ERK pathway involved in cell division and growth. This pathway is often overactive in Neurofibromatosis type 1 (NF1) due to mutations in the NF1 gene, leading to tumor growth. By inhibiting MEK, these drugs can reduce the growth and proliferation of tumors associated with NF1. This is particularly important for NF1 patients as it offers a targeted treatment option that can manage symptoms and improve quality of life, especially for those with inoperable tumors.

What side effects are associated with this type of intervention?

The granule formulation of selumetinib being studied for children with NF1-related symptomatic, inoperable plexiform neurofibromas (PN) aims to define a dosing regimen and assess safety. Common side effects of treatments for Neurofibromatosis, particularly those involving similar formulations, may include gastrointestinal issues (nausea, vomiting), skin reactions (rash, itching), and musculoskeletal pain. These side effects are generally mild to moderate in severity.

What prior FDA approvals exist?

The FDA has approved selumetinib (Koselugo) for the treatment of pediatric patients aged 2 years and older with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas. Selumetinib is a MEK inhibitor that targets the MAPK/ERK pathway, which is often dysregulated in NF1. This approval is particularly relevant as it aligns with the ongoing study of the granule formulation of selumetinib, aimed at assessing its pharmacokinetics and safety in younger children with similar conditions.

What other types of research exist?

One promising alternative is the niosome encapsulated vincristine (NVCR), which has shown slower plasma clearance, altered tissue distribution, and reduced neuromuscular toxicity compared to free vincristine. This formulation could potentially offer a safer and more effective treatment option for Neurofibromatosis patients.

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Kinase Inhibitor

Selumetinib Granules for Neurofibromatosis (SPRINKLE Trial)

Phase 1 & 2

Waitlist Available

Research Sponsored by AstraZeneca

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Male and female participants aged ≥ 1 to < 7 years of age at the time their legally authorised representative (parent or guardian) signs the informed consent

Participants must have a BSA ≥ 0.4 and ≤ 1.09 m2 at study entry (date of ICF signature)

Must not have

Participants with clinically significant cardiovascular disease as defined in the protocol

Participants with ophthalmological findings/condition as listed in the protocol

Timeline

Screening 3 weeks

Treatment Varies

Follow Up capsule dosing day 7 (range day 4 to 14) pre-dose and 0.5, 1.5, 3, 6, and 10-12 hours post-dose

Awards & highlights

All Individual Drugs Already Approved

No Placebo-Only Group

Summary

This trial tests selumetinib granules in children aged 1 to 7 years with inoperable NF1-related tumors. The medication works by blocking signals that make the tumors grow. The study aims to find the right dose and check if it's safe and effective.

Who is the study for?

This trial is for children aged 1 to less than 7 with Neurofibromatosis Type 1 (NF1) and symptomatic, inoperable plexiform neurofibromas (PN). They must have a body surface area within specified limits and at least one measurable PN. Children who've had incomplete surgery for PN are eligible if the remaining PN can be measured. Those with certain renal, liver, or hematological issues, previous MEKi treatment complications, or inability to undergo MRI are excluded.

What is being tested?

The study tests Selumetinib granule formulation versus capsule formulation in young children with NF1-related PNs. It aims to determine appropriate dosing and assess how the drug moves through and affects the body (pharmacokinetics), its safety profile, as well as preliminary effectiveness of reducing symptoms related to these tumors.

What are the potential side effects?

While specific side effects for this age group aren't listed here, Selumetinib may generally cause skin rash, diarrhea, fatigue, nausea/vomiting among others. Side effects could vary based on individual reactions and dosage received during the trial.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am a parent or guardian of a child aged 1 to less than 7 years.

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My body surface area is between 0.4 and 1.09 square meters.

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I can do most activities, but may need help, or I use a wheelchair/breathing support but can still do some activities.

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I have a tumor that is at least 3 cm large, visible on scans, and not fully removed by surgery.

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I have NF1 with a tumor that can't be removed by surgery.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a serious heart condition as defined in the study.

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I have eye conditions listed in the study protocol.

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I stopped or reduced my MEKi treatment due to side effects or my cancer got worse.

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I cannot have an MRI due to certain conditions or devices in my body.

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I have not had radiotherapy in the last 6 weeks or on the cancer spots this study targets.

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My kidney function is reduced, with specific creatinine levels based on my age.

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I haven't taken any experimental or targeted NF1-PN treatments recently.

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I have severe nausea, vomiting, or gut issues that prevent me from taking pills properly.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ capsule dosing day 7 (range day 4 to 14) pre-dose and 0.5, 1.5, 3, 6, and 10-12 hours post-dose

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~capsule dosing day 7 (range day 4 to 14) pre-dose and 0.5, 1.5, 3, 6, and 10-12 hours post-dose

This trial's timeline: 3 weeks for screening, Varies for treatment, and capsule dosing day 7 (range day 4 to 14) pre-dose and 0.5, 1.5, 3, 6, and 10-12 hours post-dose for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Adverse Events graded by CTCAE Ver 5.0

Selumetinib AUC0-12 derived after single dose administration

Secondary study objectives

N-desmethyl selumetinib AUC0 12 derived after single dose administration

Objective Response Rate

Palatability using the parent-reported observer palatability questionnaire

+16 more

Other study objectives

Selumetinib and N-desmethyl selumetinib AUC0-12 after multiple dose administration

Selumetinib and N-desmethyl selumetinib AUC0-6 after multiple dose administration

Selumetinib and N-desmethyl selumetinib AUClast after multiple dose administration

+26 more

Awards & Highlights

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Selumetinib single armExperimental Treatment2 Interventions

This study consists of a screening period (up to 28 days), a treatment period (25 cycles) and a long term safety follow-up for participants until they are 5 years old or commence an alternative systemic NF1-PN treatment, whichever is the earlier. Participants may continue treatment with selumetinib throughout the long term safety follow-up as long as they are considered to be receiving clinical benefit in the opinion of their Investigator. A safety follow up assessment will be performed 30 days after the last dose of study intervention for all study participants.

0 / 13Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

MEK inhibitors, such as selumetinib, work by blocking the MEK enzyme, which is part of the MAPK/ERK pathway involved in cell division and growth. This pathway is often overactive in Neurofibromatosis type 1 (NF1) due to mutations in the NF1 gene, leading to tumor growth. By inhibiting MEK, these drugs can reduce the growth and proliferation of tumors associated with NF1. This is particularly important for NF1 patients as it offers a targeted treatment option that can manage symptoms and improve quality of life, especially for those with inoperable tumors.

Network meta-analyses for EGFR mutation-positive non-small-cell lung cancer: systematic review and overview of methods and shortcomings.A feasibility and efficacy study of rapamycin and erlotinib for recurrent pediatric low-grade glioma (LGG).Pharmacokinetic studies in children with cancer.