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Neurofibromatosis 2Phase 2SEL-TH-1601NCT03095248

Trial of Selumetinib in Patients With Neurofibromatosis Type II Related Tumors

A Phase 2 study testing Selumetinib in people with Neurofibromatosis 2 and Vestibular Schwannoma, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

In this research study the researchers want to learn more about the effects (both good and bad) the study drug selumetinib has on participants with neurofibromatosis type II (NF2) related tumor. Read more about this study

Who is it for?
Ages 3 to 45 years
What is being tested?
Selumetinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
1 siteUnited States
Study dates
8 May 2017to 21 May 2024
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 3 to 45 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Patients must have a confirmed diagnosis of neurofibromatosis 2 by fulfilling National Institute of Health (NIH) criteria or Manchester criteria, or by detection of a causative mutation in the NF2 gene.
  • The NIH criteria includes presence of:
  • Bilateral vestibular schwannomas, OR
  • First-degree relative with NF2 and EITHER unilateral eighth nerve mass OR two of the following: neurofibroma, meningioma, glioma, schwannoma, juvenile posterior subcapsular lenticular opacity.
  • The Manchester criteria includes presence of:
  • Bilateral vestibular schwannomas, OR
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  • First-degree relative with NF2 and EITHER unilateral eighth nerve mass OR two of the following: neurofibroma, meningioma, glioma, schwannoma, juvenile posterior subcapsular lenticular opacity, OR
  • Unilateral vestibular schwannoma AND any two of: neurofibroma, meningioma, glioma, schwannoma, juvenile posterior subcapsular lenticular opacity, OR
  • Multiple meningiomas (two or more) AND unilateral vestibular schwannoma OR any two of: schwannoma, glioma, neurofibroma, cataract.
  • Patients do not need to have a histologic diagnosis in order to start therapy but must have measurable disease (in 2 dimensions) on MRI scan to be eligible.
  • For Stratum 1: Patients must have a target VS with the following qualities:
  • Associated with a word recognition score of < 85% and > 0% AND
  • Documented progression defined as: Either progressive hearing loss or progressive tumor growth in last 18 months defined as ≥ 20% increase in volume.
  • For Stratum 2: Patients must not meet the eligibility criteria as stated for Stratum 1 and have a target lesion that has exhibited progression.
  • Progression is defined as: ≥ 25% increase in sum of the products of perpendicular diameters of lesions in the preceding 18 months; any new lesion; or clinical deterioration related to disease.
  • Patients must be able to swallow capsules
  • Age:
  • Patients must be ≥ 3 years to ≤ 45 years of age at start of treatment
  • Prior Therapy
  • Since there is no standard effective chemotherapy for patients with NF2 and vestibular schwannomas, meningiomas, or ependymomas patients may be treated on this trial without having received prior medical therapy directed at their VS, meningiomas, or ependymomas.
  • Since selumetinib is not expected to cause substantial myelosuppression, there will be no limit to number of prior myelosuppressive regimen for these NF2 patients.
  • Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, biologic therapy or radiotherapy prior to entering this study except for alopecia.
  • Myelosuppressive chemotherapy: Patients must have received their last dose of known myelosuppressive anticancer chemotherapy at least three weeks prior to study registration or at least six weeks if nitrosourea.
  • Biologic agent: Patient must have received their last dose of the biologic agent ≥ 7 days prior to study registration. For biologic agents that have a prolonged half-life, at least three half-lives must have elapsed prior to registration
  • Monoclonal antibody treatment: At least three half-lives must have elapsed prior to registration
  • Corticosteroids:
  • Patients who are receiving dexamethasone or other corticosteroids must be on a stable or decreasing dose for at least 1 week prior to registration. It is recommended that patients be off all steroid therapy or receive the least dose that will control their neurologic symptoms
  • Prior radiotherapy
  • XRT: ≥ 6 months must have elapsed if prior XRT to vestibular schwannoma or other tumor.
  • Stem Cell Transplant or Rescue without TBI:
  • No evidence of active graft vs. host disease and ≥ 3 months must have elapsed since transplant.
  • Performance Status:
  • Karnofsky ≥ 60% for patients > 16 years of age
  • Lansky ≥ 60 for patients ≤ 16 years of age.
  • Organ Function Requirements
  • Adequate Bone Marrow Function Defined as:
  • Peripheral absolute neutrophil count (ANC) ≥ 1500/μL
  • Platelet count ≥ 100,000/μL (transfusion independent, defined as not receiving platelet transfusions within a 7 day period prior to registration)
  • Hemoglobin ≥ 9 g/dL (may receive RBC transfusions)
  • Adequate Renal Function Defined as:
  • Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2 or
  • A serum creatinine ≤1.5×ULN for age and sex
  • Adequate Liver Function Defined as:
  • Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age
  • AST(SGOT)/ALT(SGPT) ≤2.5×ULN institutional upper limit of normal for age
  • Central Nervous System Function:
  • Patients with seizure disorder may be enrolled if they are receiving non-enzyme inducing anticonvulsants and the seizures are well controlled.
  • Cardiac Function
  • Adequate cardiac function defined as:
  • LVEF ≥55% by ECHO
  • QTc interval ≤450 msecs by EKG
  • Hypertension
  • Patients, 3 to < 18 years of age must have a blood pressure that is ≤ 95th percentile for age, height and gender at the time of registration.
  • Patients who are ≥18 years of age must have a blood pressure that is <140/90 mm of Hg at the time of registration.
  • Patients may be on blood pressure medication provided that it is not on the contraindicated list and that the medication has not been adjusted in the previous 3 months.
  • Growth factors: All colony forming growth factor(s) have been discontinued for at least one week prior to registration (filgrastim, sargramostim, and erythropoietin). For patients on long acting growth factors, the interval should be two weeks.
  • Inclusion of Women and Minorities Both males and females of all races and ethnic groups are eligible for this study.
  • Informed Consent:
  • All patients and/or their parents or legal guardians must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.

Who cannot join

  • Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies. The effects of selumetinib on the developing human fetus 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 and for the duration of study participation, and for four weeks after dosing with selumetinib ceases. The selumetinib manufacturer recommends that adequate contraception for male patients should be used for 16 weeks post-last dose due to sperm life cycle. Women of child-bearing potential must have a negative pregnancy test prior to study registration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
  • Note: Female subjects are considered "of child-bearing potential" if they are anatomically and physiologically capable of becoming pregnant. For girls of normal reproductive potential, the possibility of becoming pregnant requires ovulatory menstrual cycles and heterosexual intercourse. Although the timing of ovulation relative to menarche is variable, there is consistent evidence that some girls may have ovulatory cycles prior to menarche, and that, in healthy populations, regular ovulation may begin within a few months of menarche. Therefore, menarche is the most feasible clinical indicator of the biological potential for pregnancy.
  • Male patients with sexual partners who are pregnant or who could become pregnant (i.e. women of child-bearing potential) must use acceptable, effective and reliable methods of contraception during the study and for at least 12 weeks after the last dose of selumetinib or for longer if required, depending on the prescribing information of the combination or concomitantly administered medications.
  • Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction) that is likely to interfere with the study procedures or results
  • Patients who are currently receiving another investigational drug within 4 weeks prior to the first dose of study treatment, or within a period during which the investigational drug or systemic anticancer treatment has not been cleared from the body (e.g. a period of 5 'half-lives'), whichever is the most appropriate and as judged by the investigator are not eligible.
  • Patients who have taken another BRAF inhibitor such as Vemurafenib or Dabrafenib prior to study registration are not eligible. Prior treatment with selumetinib or another MEK inhibitor is not allowed.
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  • Patients with QTc interval of > 450 msec
  • Patients who require enzyme inducing anti-convulsants to control seizures.
  • Anticoagulation: Patients receiving coumadin are eligible but must have their PT and INR monitored prior to each 4 week course.
  • Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.
  • The following cardiac conditions:
  • Uncontrolled hypertension in adults (BP ≥ 140/90 mmHg despite medical therapy) b. Acute coronary syndrome within 6 months prior to starting treatment c. Uncontrolled Angina - Canadian Cardiovascular Society grade II-IV despite medical therapy (Appendix H) d. Symptomatic heart failure NYHA Class II-IV, prior or current cardiomyopathy, or severe valvular heart disease (Appendix I) e. Prior or current cardiomyopathy including but not limited to the following: i. Known hypertrophic cardiomyopathy ii. Known arrhythmogenic right ventricular cardiomyopathy
  • Previous moderate or severe impairment of left ventricular systolic function (LVEF <45% on echocardiography or equivalent on MuGA) if known even if full recovery has occurred.
  • Severe valvular heart disease h. Baseline Left ventricular ejection fraction (LVEF) below the LLN or <50% measured by echocardiography or institution's LLN for MUGA i. Atrial fibrillation with a ventricular rate >100 bpm on ECG at rest
  • Ophthalmological conditions as follows:
  • Current or past history of retinal pigment epithelial detachment (RPED)/central serous retinopathy (CSR) or retinal vein occlusion
  • Intraocular pressure (IOP) > 21 mmHg or uncontrolled glaucoma (irrespective of IOP)
  • Major surgery within 4 weeks of starting selumetinib. Portacath insertion, G Tube placement, and insertion of ventriculoperitoneal shunt are not considered major surgeries.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to selumetinib or combination medications or any excipient of these medicinal products.
  • History of a medical or psychiatric illness, that in the investigator's judgment renders the patient incapable of further therapy on this protocol
  • Patients with progressive disease associated with significant or disabling clinical symptoms requiring immediate intervention with surgery or radiation therapy are not eligible.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

Other trials in United States

About this study

Official title: Phase 2 Trial of Selumetinib in Patients With Neurofibromatosis Type II Related Tumors

In this research study the researchers want to learn more about the effects (both good and bad) the study drug selumetinib has on participants with neurofibromatosis type II (NF2) related tumor.

The researchers are asking patients with NF2 related tumors to be in the study, because their hearing has decreased and/or their NF2 related tumor has started to grow.

Read more

The goals of this study are:

  • Determine if selumetinib will stop NF2 related tumors from growing
  • Measure the changes in hearing after receiving selumetinib for 6 months.
  • Determine if selumetinib improves how participants feel (physically and emotionally) and how participants can perform daily activities.
  • Examine tumor tissue, if available, in a laboratory to see if NF2 related tumors have targets of selumetinib.
Read the detailed description

This is a Phase 2 trial to assess the hearing response rate and radiographic response of VS in children and young adults with NF2 who are treated with selumetinib. Dosing will be based on BSA calculated at the beginning of each course.

Selumetinib is taken orally twice a day continuously. One course is equivalent to 28 days. Therapy may continue for up to two years (26 courses) in the absence of disease progression or unacceptable toxicity. Dose modifications will be based on Body Surface Area (BSA).

In December, 2022 the investigator closed the Stratum 1 arm. Stratum 2 is reserved for patients who exhibit growth of a tumor(s) besides vestibular schwannoma.

Being tested
Selumetinib
Medical subject headings
Neurofibromatosis 2, Neuroma, Acoustic, Meningioma, Ependymoma, Glioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SelumetinibDrug

    Also called AZD6244

    Continuous twice daily dosing; oral agent

Study groups in NCT03095248
Study groupRoleWhat they receive
Stratum 1 - NF2 related vestibular schwannomasExperimentalStratum 1 included patients with NF2 with vestibular schwannomas who exhibit hearing loss. Participants received continuous twice daily dosing of selumetinib. Dosing was based on BSA calculated at the beginning of each course. One course is equivalent to 28 days. Therapy continued for up to two years (26 courses) in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Selumetinib
Stratum 2: other NF2 related tumors (meningiomas and ependymoma)ExperimentalStratum 2 will include patients who have progressive lesions other than VS (including non-vestibular schwannomas, meningiomas, and spinal cord lesions). Participants will receive continuous twice daily dosing of selumentinib. Dosing is based on BSA calculated at the beginning of each course. One course is equivalent to 28 days. Therapy may continue for up to two years (26 courses) in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Selumetinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Stratum 1- Number of Patients With Hearing Response at 24 Weeks as Measured by Word Recognition

    The primary endpoint for the Stratum 1 is hearing response at 24 weeks, defined as an improvement in word recognition score above the 95% critical difference, taking as reference the baseline word recognition score. Audiology will include measurement of pure tone thresholds and determination of word recognition scores. Word recognition scores measure the ability to recognize (as opposed to detect) auditory information. Patients are presented a list of 50 words at a fully audible level and the percentage identified correctly is the score. This study will use full 50-item monosyllable lists and standardized recordings.

    This Outcome Measure was pre-specified to be assessed only within the Stratum 1 Arm/Group.

    Measured: 24 weeks

  2. Radiographic Tumor Response

    To determine the radiographic response rate for Stratum 1 and Stratum 2. Specifics for each stratum are defined in the Arms/ Groups.

    Measured: Through study completion up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Mar 2017
  2. Study start8 May 2017
  3. Primary completion21 May 2024
  4. Study completion21 May 2024

Why it stopped: Results review of patient data

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
All participants with neurofibromatosis type 2 (NF2) will be stratified based upon tumor type. Vestibular schwannomas are assigned and analyzed as Stratum 1 and all other NF2 associated tumor types will be analyzed as Stratum 2.
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03095248
Sponsor's protocol ID
SEL-TH-1601
Other IDs
2016-8833
Acronym
SEL-TH-1601
Status last verified
Apr 2025
First submitted
8 Mar 2017
Last updated
22 Apr 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Selumetinib in people with Neurofibromatosis 2 and Vestibular Schwannoma, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 59 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 22 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Apr 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Stratum 1- Number of Patients With Hearing Response at 24 Weeks as Measured by Word Recognition (time frame: 24 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03095248.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Apr 2025.

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