Selumetinib for Neurofibromatosis

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

36 Participants Needed

Trial Summary

What is the purpose of this trial?

Background: Neurofibromatosis type 1 (NF1) is a disorder that can cause plexiform neurofibromas (PNs). These are tumors that grow along nerves. Some PNs cause serious health problems. PNs often can t be operated on because of their large size, location, or number. There are no effective treatments known for people with NF1 and PNs. Researchers want to test if the drug selumetinib (AZD6244 hydrogen sulfate) causes PNs to shrink or slows down their growth. Objectives: To test if selumetinib helps treat PNs. To test how the body handles selumetinib and how it affects peoples symptoms. Eligibility: People ages 18 and older with NF1, with an inoperable PN that causes morbidity or is growing Design: Participants will be screened with: Medical history and physical exam Blood, urine, and heart tests Eye exam MRI: They lie in a machine that takes pictures of the body. PN biopsy: A small piece of the tumor is removed by a large needle. Questionnaires Participants will swallow selumetinib capsules every 12 hours for several 28-day cycles. The capsules are taken with a full glass of water on an empty stomach. Participants may have only water for 2 hours before and 1 hour after each dose. Participants will keep a drug diary. They will continue taking the drug as long as they tolerate it and their disease doesn t progress. Participants will have several visits throughout the study. These will include repeats of the screening tests. Participants will have a final visit after they stop taking selumetinib.

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 Selumetinib safe for humans?

Selumetinib has been approved by the FDA for treating children with neurofibromatosis type 1 and inoperable plexiform neurofibromas, and its safety has been evaluated in both children and adults. Common side effects include issues with eyes, heart, muscles, stomach, and skin, which are typical for its class of drugs. ^{1 2 3 4 5}

What makes the drug Selumetinib unique for treating neurofibromatosis type 1?

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. This drug offers a non-surgical option for managing these tumors, which are often difficult to remove surgically. ^{1 2 3 4 6}

Research Team

Brigitte C Widemann, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

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

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

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

Selumetinib: First Approval. [2021]

3. 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]

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

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

5. Germany pubmed.ncbi.nlm.nih.gov

Population pharmacokinetics and exposure-response of selumetinib and its N-desmethyl metabolite in pediatric patients with neurofibromatosis type 1 and inoperable plexiform neurofibromas. [2021]

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

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