Selumetinib in Treating Patients With Neurofibromatosis Type 1 and Cutaneous Neurofibroma

  • End date
    Dec 31, 2021
  • participants needed
  • sponsor
    National Cancer Institute (NCI)
Updated on 3 September 2021
absolute neutrophil count
growth factor
neutrophil count
tumor cells
vascular endothelial growth factor
gilbert disease


This pilot phase II trial studies how well selumetinib works in treating patients with neurofibromatosis type 1 and cutaneous neurofibromas. Selumetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.



I. Determine if selumetinib can result in shrinkage of cutaneous neurofibromas.


I. Assess the effect of selumetinib on target inhibition in cutaneous neurofibroma(s) excised prior treatment and on treatment with selumetinib for analysis of percent inhibition of phosphorylated ERK (pERK), and changes in phosphorylated AKT (pAKT).


I. Assess the effect of selumetinib on the development on new cutaneous neurofibromas while on treatment with selumetinib.

II. Assess the effect of selumetinib on target inhibition in cutaneous neurofibroma(s) excised prior treatment and on treatment with selumetinib for analysis of the tumor kinome.

III. Assess the effect of selumetinib skin related morbidity and pain using the Skindex, the Global Impression of Change Scale and Numeric Rating Scale, all of which are patient reported outcome measures.

IV. Quantify the development of new cutaneous neurofibromas on treatment with selumetinib.

V. Detailed pathologic analysis of cutaneous neurofibromas pretreatment and on treatment with selumetinib for changes in cell composition (including macrophage and mast cell infiltration).

VI. Investigate alterations that correlate with cutaneous neurofibroma (cNF) response to selumetinib treatment with pilot genomic, deoxyribonucleic acid (DNA) methylation, and transcriptomic studies.


Patients receive selumetinib orally (PO) twice daily (BID) on days 1-28. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients who experience a volume decrease in the target cutaneous neurofibromas may continue treatment for 12 additional cycles.

After completion of study treatment, patients are followed up every 4 months for 1 year.

Condition Optic Nerve Glioma, Neurofibromatosis, von Recklinghausen's Disease, Cafe au lait spots, Glioma, Peripheral Neuropathy, Dysplasia, Appearance Distress, Bothered by Itching Skin, Cutaneous Neurofibroma, Disfigurement, Lisch Nodule, NF1 Gene Mutation, Gliomas, optic gliomas
Treatment laboratory biomarker analysis, Selumetinib, Selumetinib Sulfate
Clinical Study IdentifierNCT02839720
SponsorNational Cancer Institute (NCI)
Last Modified on3 September 2021


Yes No Not Sure

Inclusion Criteria

Patients must have a documented germline neurofibromatosis 1 (NF1) mutation in a Clinical Laboratory Improvement Act (CLIA) certified laboratory or a diagnosis of NF1 based on clinical National Institutes of Health (NIH) consensus criteria; in addition to substantial cutaneous neurofibroma burden, at least one of the criteria below have to be present
Six or more cafe-au-lait macules (>= 0.5 cm in prepubertal subjects or >= 1.5 cm in post pubertal subjects)
Freckling in axilla or groin
Optic glioma
Two or more Lisch nodules
A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex)
A first-degree relative with NF1
Histologic confirmation of tumor is not necessary in the presence of consistent clinical findings
Patients must have substantial cutaneous neurofibroma burden causing distress to the patient by disfigurement or itching; patients must have >= 9 measurable cutaneous neurofibromas; for the purpose of this study measurability will be defined for each of the lesions selected as target lesions as a neurofibroma with a longest diameter >= 4 mm in the longest diameter
Eastern Cooperative Oncology Group (ECOG) performance status =< 2
Hemoglobin >= 10 g/dL (not requiring red blood cell [RBC] transfusions)
Absolute neutrophil count >= 1,500/mcL
Platelets >= 100,000/mcL (not requiring platelet transfusions)
Total bilirubin =< 1.5 X upper limit of normal (ULN), with the exception of patients with Gilbert syndrome who are required to have =< 3 X ULN
Alanine transferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3.0 X ULN
Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
Ability of subject or legally authorized representative (LAR) to understand and the willingness to sign a written informed consent document
Willingness to avoid excessive sun exposure and use adequate sunscreen protection if sun exposure is anticipated
Willingness to avoid the ingestion of grapefruit and Seville oranges (as well as other products containing these fruits, e.g. grapefruit juice or marmalade) during the study
Since there is no standard effective chemotherapy for patients with NF1 and cutaneous neurofibromas, patients may be treated on this trial without having received prior medical therapy directed at their plexiform neurofibromas (PN)
Since selumetinib is not expected to cause substantial myelosuppression, there will be no limit to number of prior myelosuppressive regimens previously received for NF1 related; or other tumor manifestations
Patients who have received previous investigational agents or biologic therapy, such as tipifarnib, pirfenidone, Peg-intron, sorafenib, or other vascular endothelial growth factor (VEGFR) inhibitors are eligible for enrollment
Growth factors that support platelet or white cell number or function must not have been administered within the past 7 days and are not permitted while on the study
At least 6 weeks must have elapsed prior to enrollment since the patient received any prior radiation therapy, and the target cutaneous neurofibromas have to be in areas outside of a prior radiation field
At least 4 weeks must have elapsed since receiving medical therapy directed at NF1 related tumor manifestations
At least 4 weeks must have elapsed since any surgeries, with evidence of completed wound healing
Patients who received prior medical therapy for a NF1 related tumor must have recovered from the acute toxic effects of all prior therapy to =< grade 1 Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0 before entering this study
The effects of selumetinib on the developing human fetus at the recommended therapeutic dose are unknown; for this reason women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 4 weeks after dosing with selumetinib ceases; women of child-bearing potential must have a negative pregnancy test prior to entry; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, the patient should inform her treating physician immediately; please note that the selumetinib manufacturer recommends that adequate contraception for male patients should be used for 12 weeks post-last dose due to sperm life cycle
Diagnostic or laboratory studies performed exclusively to determine eligibility for this trial must only be done after obtaining written informed consent from all patients, which can be accomplished using the study specific informed consent or another consent, such as the National Cancer Institute (NCI), Pediatric Oncology Branch (POB) screening protocol; studies or procedures that were performed for clinical indications (not exclusively to determine eligibility) may be used for screening or baseline values even if the studies were done before informed consent was obtained, if the patient agrees

Exclusion Criteria

Patients who are receiving any other investigational agents, or have received an investigational agent within the past 30 days
May not have a NF1 related tumor such as optic pathway glioma or malignant peripheral nerve sheath tumor, which requires treatment with chemotherapy, radiation, or surgery
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, active bleeding diatheses or renal transplant, including any patient known to have hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements; patients with HIV who have adequate cluster of differentiation (CD)4 counts and who have no requirement for antiviral therapy will be eligible
Pregnant or breast-feeding females are excluded due to potential risks of fetal and teratogenic adverse events of an investigational agent; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method; abstinence is an acceptable method of birth control
Prior treatment with selumetinib or another specific MEK 1/2 inhibitor
No supplementation with vitamin E is permitted
Inability to swallow capsules, since capsules cannot be crushed or broken
Refractory nausea and vomiting, chronic gastrointestinal diseases (e.g., inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption
Strong inhibitors or inducers of hepatic microsomal isoenzymes
While not an exclusion criterion, unless clinically indicated, patients should avoid taking other additional non-study medications that may interfere with the study medications; in particular, patients should avoid medications that are known to strong inhibitor or inducers of hepatic microsomal isoenzymes CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP3A4/5, UGT1A1, UGT1A3 and transporters BCRP and P-gp
Known cardiac disorder, including
Uncontrolled hypertension (blood pressure [BP] of >= 150/95 despite medical support/management)
Acute coronary syndrome within 6 months prior to starting treatment
Uncontrolled angina - Canadian Cardiovascular Society grade II-IV despite medical support/management
Heart failure New York Heart Association (NYHA) class II or above
Prior or current cardiomyopathy including but not limited to the following
Known hypertrophic cardiomyopathy
Known arrhythmogenic right ventricular cardiomyopathy
Baseline left ventricular ejection fraction (LVEF) =< 53%
Previous moderate or severe impairment of left ventricular systolic function (LVEF < 40% on echocardiography or equivalent on multi-gated acquisition scan [MUGA]) even if full recovery has occurred
Severe valvular heart disease
Atrial fibrillation with a ventricular rate > 100 beats per minute (bpm) on electrocardiography (ECG) at rest
Fridericia's correction formula (QTcF) interval > 450 msec or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome) are excluded; the use of medication(s) that can prolong corrected QT (QTc) interval is prohibited while treated on this study
Known ophthalmologic conditions, such as
Current or past history of retinal pigment epithelial detachment (RPED)/central serous retinopathy (CSR)
Current or past history of retinal vein occlusion
Known intraocular pressure (IOP) > 21 mmHg (or ULN adjusted by age) or uncontrolled glaucoma (irrespective of IOP); patients with controlled glaucoma and increased IOP who do not have meaningful vision (light perception only or no light perception) may be eligible after discussion with the study chair
Subjects with any other significant abnormality on ophthalmic examination (performed by an ophthalmologist) should be discussed with the study chair for potential eligibility
Ophthalmological findings secondary to long-standing optic pathway glioma (such as visual loss, optic nerve pallor or strabismus) or long-standing orbito-temporal PN (such as visual loss, strabismus) will NOT be considered a significant abnormality for the purposes of the study
Known severe hypersensitivity to selumetinib or any excipient of selumetinib or history of allergic reactions attributed to compounds of similar chemical or biologic composition to selumetinib
Have had recent major surgery within a minimum of 4 weeks prior to starting study treatment, with the exception of surgical placement for vascular access
Have any unresolved chronic toxicity with CTCAE grade >= 2, from previous anti-NF1 therapy, except for alopecia
Clinical judgment by the investigator that the patient should not participate in the study
Clear my responses

How to participate?

Step 1 Connect with a site
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact


Preferred Language
Other Language
Please verify that you are not a bot.

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider


Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 



Reply by • Private

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note