Selumetinib for Pediatric Brain Cancer

Not currently recruiting at 18 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Anticancer agents, MEK inhibitors

Disqualifiers: Uncontrolled seizures, Significant organ dysfunction, 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: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests selumetinib, a drug that might help treat young patients with certain types of brain cancer, specifically low-grade glioma, which has returned or isn't responding to other treatments. The goal is to determine the best dose and evaluate its effectiveness in stopping tumor growth. Ideal participants are young patients with low-grade glioma that has either returned or isn't responding to other treatments, and whose tumors have been tested for specific genetic markers related to the BRAF gene. As a Phase 1, Phase 2 trial, this research aims to understand how selumetinib works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on other anticancer or investigational agents, and certain medications that prolong the QT interval are not allowed. It's best to discuss your current medications with the trial team.

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

Earlier studies have found selumetinib to be generally safe and well-tolerated in children. Research shows that when treating children with certain tumors, such as those related to NF1 (a genetic disorder causing tumors on nerve tissues), selumetinib did not raise new safety concerns.

The FDA has approved selumetinib for young patients with NF1, indicating a strong safety record. In these approved cases, children experienced side effects, but they were usually manageable. This approval suggests that selumetinib can be used safely in children, even though the specific condition in this trial differs.

So far, evidence shows that selumetinib is safe for children and can be tolerated over long-term use. However, like any treatment, it may still cause side effects, so discussing expectations with doctors is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Selumetinib is unique because it targets a specific part of the cancer cell's machinery called the MEK pathway, which plays a critical role in cell growth and survival. Unlike standard treatments for pediatric brain cancer, which often rely on chemotherapy or radiation, selumetinib is a targeted therapy that interferes directly with the cancer's growth signals. Researchers are excited about selumetinib because it offers a more precise approach, potentially leading to fewer side effects and improved outcomes for young patients battling brain cancer.

What evidence suggests that selumetinib might be an effective treatment for pediatric brain cancer?

Research has shown that selumetinib, the treatment under study in this trial, offers promising results for pediatric low-grade gliomas, a type of brain tumor in children. In earlier studies, selumetinib shrank tumors and halted their growth. Some patients experienced improvements in vision and overall stability. Another study found that selumetinib blocked certain proteins that promote tumor growth, leading to better outcomes. These findings suggest that selumetinib could be effective for children whose tumors have recurred or do not respond to other treatments. ^{1 6 7 8 9}

Who Is on the Research Team?

Jason R Fangusaro

Principal Investigator

Pediatric Brain Tumor Consortium

Are You a Good Fit for This Trial?

This trial is for young patients aged 3-21 with recurrent or refractory low grade glioma, including various types of brain tumors like astrocytoma. Participants must have specific tumor characteristics confirmed by recent tests and be willing to provide tissue samples for genetic testing.

Inclusion Criteria

I haven't taken any growth factor medications for at least 1 or 2 weeks.

Absolute neutrophil count >= 1,000/uL (unsupported) (within 14 days of registration and within 7 days of the start of treatment)

Platelets >= 100,000/L (unsupported) (within 14 days of registration and within 7 days of the start of treatment)

Exclusion Criteria

I have seizures that are not controlled by medication.

I have been treated with a BRAF inhibitor before, but not sorafenib.

I do not have any serious illnesses that could affect the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive selumetinib orally twice daily on days 1-28. Cycles repeat every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity.

24 months

Re-treatment

Patients who experience a sustained objective response and have completed 2 years of treatment may be enrolled on the re-treatment study after progression/recurrence. Treatment continues indefinitely in the absence of disease progression or unacceptable toxicities.

Indefinite

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Selumetinib

Trial Overview

The trial is examining the effects and optimal dosage of Selumetinib, a drug intended to inhibit tumor growth by blocking enzymes necessary for cell proliferation. It's designed as a phase I/II study to determine side effects and effectiveness in children and young adults.

How Is the Trial Designed?

Group I: Treatment (selumetinib) Experimental Treatment 2 Interventions

Patients receive selumetinib PO BID on days 1-28. Cycles repeat every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity. Patients who experience a sustained objective response from selumetinib on the phase I or phase II portions of the trial, and who have completed 2 years of treatment and stopped study drug may be enrolled on the re-treatment study after progression/recurrence. Patients in the re-treatment study may continue treatment indefinitely in the absence of disease progression or unacceptable toxicities. Patients undergo blood sample collection on study.

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+

Published Research Related to This Trial

Selumetinib, a MEK 1/2 inhibitor, shows promise in treating pediatric low-grade gliomas, with ADC histogram metrics correlating with treatment response and progression-free survival in children with specific tumor types.

In particular, responders to selumetinib treatment exhibited significant decreases in ADC metrics over time, suggesting that these imaging biomarkers could help predict which patients are likely to benefit from the therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ADC Histogram Analysis of Pediatric Low-Grade Glioma Treated with Selumetinib: A Report from the Pediatric Brain Tumor Consortium. Vajapeyam, S., Brown, D., Ziaei, A., et al.[2023]

In a study using the BT-40 low-grade childhood astrocytoma xenograft model, resistance to the MEK inhibitor selumetinib was found to be unstable, with tumors reverting to sensitivity when not treated, indicating potential for effective treatment strategies.

Combining selumetinib with a STAT3 inhibitor (LLL12) led to complete tumor regressions in selumetinib-resistant xenografts, suggesting that targeting both BRAF(V600E) and STAT3 pathways could be a promising approach to overcome drug resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development, characterization, and reversal of acquired resistance to the MEK1 inhibitor selumetinib (AZD6244) in an in vivo model of childhood astrocytoma. Bid, HK., Kibler, A., Phelps, DA., et al.[2021]

In a phase I/II study involving 139 pediatric patients with relapsed/refractory malignancies, trametinib was found to have a recommended dose of 0.032 mg/kg for children under 6 years and 0.025 mg/kg for those 6 years and older, with manageable safety profiles and no dose-limiting toxicities when combined with dabrafenib.

Among 49 patients with BRAF V600-mutant low-grade gliomas, the combination therapy of dabrafenib and trametinib showed a higher objective response rate of 25% compared to 15% for trametinib alone, indicating improved efficacy with the combination treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Trametinib Monotherapy or in Combination With Dabrafenib in Pediatric BRAF V600-Mutant Low-Grade Glioma. Bouffet, E., Geoerger, B., Moertel, C., et al.[2023]

In a multicenter phase 2 study involving 50 patients with recurrent or progressive pediatric low-grade glioma, selumetinib demonstrated significant activity, with 36% of patients in the BRAF aberration group and 40% in the NF1-associated group achieving a sustained partial response.

Selumetinib was well-tolerated, with no treatment-related deaths reported, and the most common serious side effects were manageable, suggesting it could serve as a safer alternative to standard chemotherapy for these specific patient groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selumetinib in paediatric patients with BRAF-aberrant or neurofibromatosis type 1-associated recurrent, refractory, or progressive low-grade glioma: a multicentre, phase 2 trial. Fangusaro, J., Onar-Thomas, A., Young Poussaint, T., et al.[2020]

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8485450/

A phase II trial of selumetinib in children with recurrent optic ...

This study highlights that selumetinib led to both radiographic responses and stable disease as well as visual stability and improvement in patients with ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC5570236/

A phase I trial of the MEK inhibitor selumetinib (AZD6244) in ...

BRAFV600E PA xenograft model studies demonstrated tumor regression and prolonged event-free survival,15 while adult studies have demonstrated promising ...

3.

withpower.com

withpower.com/trial/selumetinib-for-pediatric-brain-cancer-5539b

Selumetinib for Pediatric Brain Cancer · Info for Participants

Selumetinib has shown promising results in treating pediatric low-grade gliomas, a type of brain tumor, by targeting specific proteins involved in tumor growth.

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT01089101

Study Details | NCT01089101 | Selumetinib in Treating ...

Selumetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. OUTLINE: This is a phase I dose-escalation study ( ...

5.

academic.oup.com

academic.oup.com/neuro-oncology/article/26/Supplement_4/0/7695094

LGG-05. REPORT ON PEDIATRIC BRAIN TUMOR ...

Two-year progression-free survival (PFS)/overall survival (OS) were 57.1/100%, respectively. Stratum 5: among 23 patients, there was 1 complete ...

6.

oncologynewscentral.com

oncologynewscentral.com/drugs/info/fda-expands-selumetinib-use-to-younger-children-with-nf1-tumors

FDA Expands Selumetinib Use to Younger Children With ...

The safety section was updated with data from a larger pediatric population, although no new concerns emerged. The recommended dose is 25 mg/m2 ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10547508/

Long-term safety and efficacy of selumetinib in children with ...

Thus, these results show that treating children with selumetinib for symptomatic, inoperable NF-related PN is safe, tolerable, and often provides durable ...

8.

onclive.com

onclive.com/view/fda-approves-selumetinib-for-symptomatic-pediatric-nf-1-associated-inoperable-plexiform-neurofibromas

FDA Approves Selumetinib for Symptomatic Pediatric NF-1 ...

Selumetinib is approved for pediatric patients with NF1 with inoperable plexiform neurofibromas, based on bioavailability and efficacy studies.

9.

koselugo.com

koselugo.com/

Koselugo® (selumetinib) | Official Caregiver Website

... Koselugo is safe and effective in children under 2 years of age. Please see Patient Information in the full Prescribing Information for Koselugo (selumetinib).