Selumetinib Granules for Neurofibromatosis

(SPRINKLE Trial)

Not currently recruiting at 42 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: < 18

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: AstraZeneca

Must not be taking: MEKi, Herbal supplements

Disqualifiers: Malignant glioma, Cardiovascular disease, 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: Unknown

Duration: 25 cycles (each cycle is 28 days)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a medication called Selumetinib (also known as Koselugo, AZD6244, or ARRY-142886) for children with Neurofibromatosis Type 1 (NF1), a condition that causes tumors not removable by surgery. The trial aims to determine the right dose, assess how the body processes the medicine, and evaluate its effect on symptoms. It specifically targets children with noticeable, problematic tumors visible on scans. Participants will use the medicine over several treatment cycles, with progress and safety monitored throughout. This trial offers an opportunity for children with NF1 who have inoperable tumors causing symptoms. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, allowing participants to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires that participants stop taking herbal supplements or medications that strongly affect certain liver enzymes (CYP3A4 and CYP2C19) at least 14 days before starting the study medication. If you are taking such medications, you may need to stop them.

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

Research has shown that selumetinib is generally safe for children with neurofibromatosis type 1 (NF1) who have plexiform neurofibromas (PNs) that cannot be surgically removed. In earlier studies, children who took selumetinib for up to five years experienced positive results with manageable side effects. The FDA has approved selumetinib for children as young as 1 year old for this condition, indicating a well-understood safety profile for young patients. While some side effects, such as stomach issues or skin problems, may occur, selumetinib has demonstrated a good safety record in past clinical use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for neurofibromatosis, which often involve surgery or radiation, selumetinib is an oral medication that targets a specific pathway involved in tumor growth. This drug is a MEK inhibitor, meaning it blocks the MEK enzymes that contribute to the development of tumors in neurofibromatosis type 1. Researchers are excited about selumetinib because it offers a non-invasive option that can potentially shrink tumors and improve symptoms, providing a new avenue of hope for patients with this challenging condition.

What evidence suggests that Selumetinib might be an effective treatment for Neurofibromatosis?

Research has shown that selumetinib can reduce tumor size in people with neurofibromatosis type 1 (NF1) who cannot undergo surgery. Studies have found that it not only decreases tumor size but also provides pain relief. Selumetinib has proven effective in both adults and children, leading to significant tumor shrinkage. Testing has confirmed its safety, and it is considered safe to use. Notably, it is the first treatment approved by the FDA specifically for shrinking these tumors in children. These findings suggest that selumetinib could be a promising option for managing NF1-related tumors. Participants in this trial will receive selumetinib to further evaluate its effectiveness and safety in this population. ^{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?

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.

Inclusion Criteria

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

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

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

Exclusion Criteria

Liver function tests: Bilirubin > 1.5 × the ULN for age with the exception of those with Gilbert syndrome (≥ 3 × ULN) or AST/ALT > 2 × ULN

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

I have eye conditions listed in the study protocol.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive selumetinib for 25 cycles to evaluate pharmacokinetics, safety, and tolerability

25 cycles (each cycle is 28 days)

Safety Follow-up

Participants are monitored for safety and effectiveness after treatment, continuing until they reach the age of 5 years or commence an alternative treatment

What Are the Treatments Tested in This Trial?

Interventions

• Selumetinib

Trial Overview 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.

How Is the Trial Designed?

Group I: Selumetinib single arm Experimental Treatment 2 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.

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

Capmatinib (Tabrecta) is FDA-approved for treating metastatic non-small cell lung cancer in adults with specific mutations, but patients must be monitored for serious side effects like interstitial lung disease and hepatotoxicity.

Fam-trastuzumab deruxtecan-nxki (Enhertu) has also received accelerated FDA approval for a different type of metastatic non-small cell lung cancer, with warnings about risks such as interstitial lung disease and embryo-fetal toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two New Drugs Approved for Non-Small Cell Lung Cancer. Aschenbrenner, DS.[2023]

Afatinib, an irreversible pan-ErbB inhibitor, has been approved for treating advanced non-small cell lung cancer (NSCLC) with specific EGFR mutations, showing promise in overcoming resistance to first-generation EGFR inhibitors like gefitinib and erlotinib.

Clinical studies indicate that afatinib is well tolerated, with side effects similar to those of first-generation EGFR TKIs, including diarrhea and rash, while providing effective treatment options for patients with sensitizing mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Afatinib for the treatment of metastatic non-small cell lung cancer. Joshi, M., Rizvi, SM., Belani, CP.[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]

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]

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

2. 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 ...

3. 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.

4. 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) ...

5. koselugohcp.com koselugohcp.com/efficacy

Koselugo® (selumetinib) | Efficacy Koselugo is the FIRST FDA-approved treatment proven to shrink NF1 PN in pediatric patients · Primary endpoint: Overall response rate1* · Substantial reduction in ...

6. koselugohcp.com koselugohcp.com/safety

Koselugo® (selumetinib) | Safety KOSELUGO is indicated for the treatment of pediatric patients 2 years of age and older with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable ...

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. koselugo.com koselugo.com/

Koselugo® (selumetinib) | Official Caregiver Website KOSELUGO® (selumetinib) is the first FDA-approved therapy proven to shrink plexiform neurofibromas in children and teens. Koselugo is a prescription medicine ...

9. 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 ...