What side effects are associated with this type of intervention?

The most common treatments for Neurofibromatosis, particularly with MEK inhibitors like Selumetinib, include side effects such as gastrointestinal symptoms (nausea, vomiting, diarrhea), fatigue, skin rash, and elevated liver enzymes. These side effects are generally manageable but require monitoring and supportive care to ensure patient safety.

What prior FDA approvals exist?

Selumetinib, a MEK inhibitor, has been approved by the FDA for the treatment of symptomatic, inoperable plexiform neurofibromas in patients with Neurofibromatosis type 1 (NF1). This approval marks a significant advancement as it is one of the first targeted therapies for NF1. Other investigational treatments for Neurofibromatosis include mTOR inhibitors like everolimus, which have shown promise in clinical trials for managing tumor growth in NF1 and NF2-related conditions.

What other types of research exist?

Promising novel alternatives to Selumetinib for Neurofibromatosis patients include MEK inhibitors like Trametinib and Binimetinib, which are being investigated for their efficacy and safety. Additionally, other targeted therapies such as mTOR inhibitors (e.g., Everolimus) and tyrosine kinase inhibitors (e.g., Cabozantinib) are also being explored in clinical trials and may offer potential benefits.

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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

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I am 18 or older with NF1 and have a tumor that can't be surgically removed.

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I have a tumor that cannot be removed by surgery and can be measured by MRI.

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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:

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I do not have serious heart problems.

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I have been treated with MEK inhibitors before.

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I have eye conditions like high pressure, retinal issues, or vein occlusion.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ approximately 3 years

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%

Hypophosphatemia

19%

Hyponatremia

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

Anorexia

Hypoglycemia

Acute kidney injury

Death, NOS

Periorbital edema

Skin hypopigmentation

Pain in extremity

Cough

Insomnia

Alkaline phosphatase increased

Dry mouth

Sepsis

Blood and lymphatic system disorders - Other

Hypernatremia

Metabolism and nutrition disorders - Other

Renal and urinary disorders - Other

Hypercalcemia

Dehydration

Musculoskeletal and connective tissue disorder - Other, Rhabdomyolysis

Chills

Hypotension

Myalgia

Arthralgia

Upper respiratory infection

Headache

Sinusitis

Generalized muscle weakness

Gastrointestinal disorders - Other

Gastroesophageal reflux disease

Vaginal inflammation

Confusion

Pruritus

Febrile neutropenia

Flu like symptoms

Hepatic failure

Skin infection

Fall

Fracture

Skin and subcutaneous tissue disorders - Other, Angular cheilitis, unilateral

Adult respiratory distress syndrome

Renal and urinary disorders - Other, Acute renal failure

INR increased

100%

80%

60%

40%

20%

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

0 / 6Eligibility 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

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.