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Kinase Inhibitor

Selumetinib for Plexiform Neurofibromas (KOMET Trial)

Phase 3
Waitlist Available
Led By Alice P. Chen, MD
Research Sponsored by AstraZeneca
Eligibility Criteria Checklist
Specific guidelines that determine who can or cannot participate in a clinical trial
Must have
Adults ≥ 18 years at enrollment with diagnosis of NF1 with symptomatic, inoperable PN
At least one inoperable target PN measurable by volumetric MRI analysis
Must not have
Clinically significant cardiovascular disease, including inherited coronary disease, acute coronary syndrome within 6 months prior to enrollment, uncontrolled angina, symptomatic heart failure, cardiomyopathy, severe valvular heart disease, abnormal LVEF and uncontrolled hypertension
Prior exposure to MEK inhibitors
Timeline
Screening 3 weeks
Treatment Varies
Follow Up approximately 3 years
Awards & highlights
Pivotal Trial

Summary

This trial is testing a medication called selumetinib to see if it can help adults with a condition called NF1 who have tumors that cause symptoms and cannot be removed by surgery. The medication works by blocking signals that make the tumors grow.

Who is the study for?
Adults over 18 with Neurofibromatosis type 1 (NF1) and symptomatic, inoperable plexiform neurofibromas can join. They must have stable pain medication use, measurable tumors by MRI, and proper organ/marrow function. Excluded are those with certain malignancies or severe heart disease.
What is being tested?
The trial is testing the effectiveness of Selumetinib versus a placebo in adults with NF1 who have painful and inoperable plexiform neurofibromas to see if it helps reduce symptoms.
What are the potential side effects?
Selumetinib may cause side effects like skin rash, eye problems, heart issues, muscle pain, fatigue, nausea/vomiting. The severity varies from person to person.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below
Select...
I am 18 or older with NF1 and have a tumor that can't be surgically removed.
Select...
I have a tumor that cannot be removed by surgery and can be measured by MRI.
Select...
My pain medication for chronic peripheral neuropathy has been stable.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:
Select...
I do not have serious heart problems.
Select...
I have been treated with MEK inhibitors before.
Select...
I have eye conditions like high pressure, retinal issues, or vein occlusion.

Timeline

Screening ~ 3 weeks
Treatment ~ Varies
Follow Up ~approximately 3 years
This trial's timeline: 3 weeks for screening, Varies for treatment, and approximately 3 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.
Primary study objectives
Confirmed Objective Response Rate (ORR) for Arm A versus Arm B
Secondary study objectives
Pain
Upper arm
Health Related Quality of Life (HRQoL) outcomes assessed using PlexiQoL
+5 more
Other study objectives
Pharmacokinetics (PK) of selumetinib for exposure-response analyses
Safety and tolerability of selumetinib as assessed by number and grade of adverse events

Side effects data

From 2012 Phase 2 trial • 37 Patients • NCT01085214
75%
Diarrhea
50%
Fatigue
47%
Anemia
47%
Rash acneiform
44%
Hypoalbuminemia
44%
Edema, limbs
39%
Aspartate aminotransferase increased
33%
Neutrophil count decreased
33%
White blood cell decreased
31%
Nausea
31%
Vomiting
28%
Platelet count decreased
25%
CPK increased
25%
Hypomagnesemia
22%
Hypertension
19%
Hyponatremia
19%
Hypophosphatemia
19%
Hypocalcemia
19%
Edema, face
17%
Dry skin
17%
Alanine aminotransferase increased
14%
Skin and subcutaneous tissue disorders - Other
14%
Hypokalemia
14%
Creatinine increased
14%
Back pain
14%
Dyspnea
14%
Lymphocyte count decreased
11%
Pain
11%
Fever
11%
Localized edema
11%
Peripheral sensory neuropathy
11%
Hyperkalemia
11%
Dizziness
11%
Abdominal pain
8%
Anorexia
8%
Hypoglycemia
8%
Acute kidney injury
8%
Death, NOS
8%
Periorbital edema
8%
Skin hypopigmentation
8%
Pain in extremity
8%
Cough
8%
Insomnia
8%
Alkaline phosphatase increased
8%
Dry mouth
8%
Sepsis
6%
Hypernatremia
6%
Metabolism and nutrition disorders - Other
6%
Blood and lymphatic system disorders - Other
6%
Renal and urinary disorders - Other
6%
Hypercalcemia
6%
Dehydration
6%
Musculoskeletal and connective tissue disorder - Other, Rhabdomyolysis
6%
Chills
6%
Hypotension
6%
Myalgia
6%
Arthralgia
6%
Upper respiratory infection
6%
Headache
6%
Sinusitis
6%
Generalized muscle weakness
6%
Gastrointestinal disorders - Other
6%
Gastroesophageal reflux disease
3%
Vaginal inflammation
3%
Confusion
3%
Pruritus
3%
Febrile neutropenia
3%
Flu like symptoms
3%
Hepatic failure
3%
Skin infection
3%
Fall
3%
Fracture
3%
Skin and subcutaneous tissue disorders - Other, Angular cheilitis, unilateral
3%
Adult respiratory distress syndrome
3%
Renal and urinary disorders - Other, Acute renal failure
3%
INR increased
100%
80%
60%
40%
20%
0%
Study treatment Arm
AZD6244 (Selumetinib) Treatment

Awards & Highlights

Pivotal Trial
The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups
Experimental Treatment
Placebo Group
Group I: Arm AExperimental Treatment1 Intervention
Selumetinib
Group II: Arm BPlacebo Group1 Intervention
Placebo
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Selumetinib
2010
Completed Phase 2
~2080

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
The most common treatments for Neurofibromatosis, particularly NF1 and NF2, include MEK inhibitors like Selumetinib, which target the MEK-ERK signaling pathway. This pathway is often overactive in Neurofibromatosis due to mutations in the NF1 or NF2 genes, leading to uncontrolled cell growth and tumor formation. By inhibiting MEK, Selumetinib helps to reduce tumor size and growth. This is crucial for Neurofibromatosis patients as it can alleviate symptoms, improve quality of life, and potentially delay or avoid the need for surgical interventions.
Clinical, genetic and pharmacological data support targeting the MEK5/ERK5 module in lung cancer.Targeted Approaches Applied to Uncommon Diseases: A Case of Salivary Duct Carcinoma Metastatic to the Brain Treated with the Multikinase Inhibitor Neratinib.Novel multi-targeted ErbB family inhibitor afatinib blocks EGF-induced signaling and induces apoptosis in neuroblastoma.

Find a Location

Who is running the clinical trial?

AstraZenecaLead Sponsor
4,378 Previous Clinical Trials
288,738,772 Total Patients Enrolled
Merck Sharp & Dohme LLCIndustry Sponsor
3,981 Previous Clinical Trials
5,177,863 Total Patients Enrolled
Alice P. Chen, MDPrincipal InvestigatorNational Cancer Institute (NCI)

Media Library

Selumetinib (Kinase Inhibitor) Clinical Trial Eligibility Overview. Trial Name: NCT04924608 — Phase 3
Neurofibromatosis Research Study Groups: Arm B, Arm A
Neurofibromatosis Clinical Trial 2023: Selumetinib Highlights & Side Effects. Trial Name: NCT04924608 — Phase 3
Selumetinib (Kinase Inhibitor) 2023 Treatment Timeline for Medical Study. Trial Name: NCT04924608 — Phase 3
~37 spots leftby Oct 2025