Neurofibromatosis Type 1Phase 1NCT04495127
Selumetinib Paediatric NF1 Japan Study
A Phase 1 study testing Selumetinib in people with Neurofibromatosis Type 1, run by AstraZeneca at 3 sites in Japan.
Trial summary
This is a phase I open label study designed to evaluate the safety, tolerability, PK and efficacy of selumetinib in Japanese paediatric patients with neurofibromatosis type 1 and inoperable and symptomatic plexiform neurofibroma. Read more about this study
- Who is it for?
- Ages 3 to 18 years
- Conditions the study is for
- Neurofibromatosis Type 1
- What is being tested?
- Selumetinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 3 sitesJapan
- Study dates
- 31 Aug 2020to 24 Mar 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Three years of age or older, and less than or equal to 18 years of age at the time of obtaining informed consent. BSA greater than or equal to 0.55 m2, and able to swallow the whole study drug (capsules) without entire contents unpacked from the capsules.
- NF1 and inoperable and symptomatic PN who have PN-related morbidities (symptom and/or complications), as judged by the investigator.
- Inoperable PN is defined as PN that cannot be surgically completely removed without risk for substantial morbidity due to encasement of, or close proximity to, vital structures, invasiveness, or high vascularity of the PN.
- A PN is defined as a neurofibroma that has grown along the length of a nerve and may involve multiple fascicles and branches. A spinal PN involves two or more levels with connection between the levels or extending laterally along the nerve.
- In addition to PN, subjects must have at least 1 other diagnostic criterion for NF1 as follows:
- Six or more café-au-lait macules >5 mm in greatest diameter in pre-pubertal individuals and >15 mm in greatest diameter in post-pubertal individuals.
Show all 13Show fewer
- Freckling in the axillary or inguinal regions.
- Optic glioma.
- Two or more Lisch nodules (iris hamartomas).
- A distinctive osseous lesion such as sphenoid dysplasia or tibial pseudarthrosis.
- A first-degree relative with NF1.
- At least one measurable typical or nodular PN in principle, defined as a lesion of at least 3 cm measured in one dimension.
- Adequate organ/haematological function
Who cannot join
- Evidence of malignant peripheral nerve sheath tumour.
- Prior malignancy (except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, low grade optic pathway gliomas associated with NF1 which does not require systemic treatment or other cancer from which the subject had been disease free for ≥2 years or which would not have limited survival to <2 years) or other cancer requiring treatment with chemotherapy or radiation therapy.
- Clinically significant cardiovascular disease
- Known history of human immunodeficiency virus, serologic status reflecting active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, or any uncontrolled active systemic infection
- Subjects with clinically significant ophthalmological findings/conditions
- Inability to undergo MRI and/or contraindication for MRI (i.e. prosthesis or orthopaedic or dental braces that would interfere with volumetric analysis of target PN on MRI).
Show all 9Show fewer
- Have refractory nausea and vomiting, chronic gastrointestinal diseases (e.g. inflammatory bowel disease), or significant bowel resection that would adversely affect the absorption/bioavailability of the orally administered study medication.
- Receiving supplementation with vitamin E greater than 100% of the daily recommended dose.
- Receiving herbal supplements or medications known to be strong inhibitors or inducers of the cytochrome P450 (CYP) 3A4 enzymes unless such products can be safely discontinued at least 14 days before the first dose of study medication.
Trial locations and contacts
3 sites in 1 country.
Japan3 sites
Research Site
Minatoku, 105-8471
Research Site
Nagoya, 466-8560
Research Site
Setagaya-ku, 157-8535
About this study
Official title: A Phase 1 Open Label Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of Selumetinib, a Selective Mitogen Activated Protein Kinase Kinase (MEK) 1 Inhibitor, in Japanese Paediatric Subjects With Neurofibromatosis Type 1 (NF1) and Inoperable and Symptomatic Plexiform Neurofibromas (PN)
This is a phase I open label study designed to evaluate the safety, tolerability, PK and efficacy of selumetinib in Japanese paediatric patients with neurofibromatosis type 1 and inoperable and symptomatic plexiform neurofibroma.
- Conditions
- Neurofibromatosis Type 1
- Being tested
- Selumetinib
- Medical subject headings
- Neurofibromatosis 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SelumetinibDrug
Selumetinib 25 mg/m2 BID
| Study group | Role | What they receive |
|---|---|---|
| Selumetinib | Experimental | Not described Receives: Drug: Selumetinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability in terms of adverse events
Number of subjects with adverse events as a measure of safety and tolerability including changes in vital signs, electrocardiograms, safety laboratory parameters, echocardiogram and ophthalmologic assessment.
Measured: From obtaining the first informed consent until 30 days after the last dose (Selumetinib). Expected duration is approximately 2 years.
Secondary outcomes (6)
Maximum plasma concentration (Cmax)
Pharmacokinetics (PK) parameters will be derived using standard non-compartmental methods.
Measured: From obtaining the first informed consent until 30 days after the last dose (Selumetinib). Expected duration is approximately two years.
Area under the plasma concentration-time curve (AUC)
Pharmacokinetics (PK) parameters will be derived using standard non-compartmental methods.
Measured: From obtaining the first informed consent until 30 days after the last dose (Selumetinib). Expected duration is approximately two years.
Overall response rate
Defined as the proportion of subjects who achieve a response by independent central review per Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) criteria.
Measured: Assessed at every 4 cycles until drug permanently discontinued. Expected duration is approximately 2 years. Each cycle is 28 days.
Duration of response
Defined as the time from the date of the first documented response (which is subsequently confirmed) until the date of documented progression or death in the absence of disease progression, as determined by independent central review per REiNS criteria.
Measured: Assessed at every 4 cycles until drug permanently discontinued. Expected duration is approximately 2 years. Each cycle is 28 days.
Clinical Global Impression of Change (CGIC)
Comprehensive evaluation will be performed by investigator on the changes of PN related morbidities (symptoms and/or complications), and relevant findings including imaging studies and physical exams from baseline.
Measured: Assessed at every 2 cycles for the first year and every 4 cycles until drug permanently discontinued. Expected duration is approximately 2 years. Each cycle is 28 days.
Total scale score of Paediatric Quality of Life Inventory (PedsQL; self- and parent-reported)
Scale scores are computed as the sum of the items divided by the number of items answered (this accounts for missing data). A Total Scale Score will also be derived as the sum of all the items divided by the number of items answered on all the scales.
Measured: Assessed at every 4 cycles until drug permanently discontinued. Expected duration is approximately 2 years. Each cycle is 28 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2020
- Study start31 Aug 2020
- Primary completion16 Jun 2021
- Study completion24 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neurofibromatosis Type 1Studies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04495127
- Sponsor's protocol ID
- D1346C00013
- Status last verified
- Apr 2023
- First submitted
- 29 Jul 2020
- Last updated
- 26 Apr 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Study at a glance
From the registry record, last updated by the sponsor on 26 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Open Label Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of Selumetinib, a Selective Mitogen Activated Protein Kinase Kinase (MEK) 1 Inhibitor, in Japanese Paediatric Subjects With Neurofibromatosis Type 1 (NF1) and Inoperable and Symptomatic Plexiform Neurofibromas (PN)
- ClinicalTrials.gov ID
- NCT04495127
- Acronym / sponsor ID
- D1346C00013
- Conditions
- Neurofibromatosis Type 1
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 31 Aug 2020 (actual)
- Primary completion
- 16 Jun 2021 (actual)
- Study completion
- 24 Mar 2023 (actual)
- First posted
- 31 Jul 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase I open label study designed to evaluate the safety, tolerability, PK and efficacy of selumetinib in Japanese paediatric patients with neurofibromatosis type 1 and inoperable and symptomatic plexiform neurofibroma.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Selumetinib | Experimental | Drug: Selumetinib |
Who may qualify
- Ages
- 3 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (13 listed)
- Three years of age or older, and less than or equal to 18 years of age at the time of obtaining informed consent. BSA greater than or equal to 0.55 m2, and able to swallow the whole study drug (capsules) without entire contents unpacked from the capsules.
- NF1 and inoperable and symptomatic PN who have PN-related morbidities (symptom and/or complications), as judged by the investigator.
- Inoperable PN is defined as PN that cannot be surgically completely removed without risk for substantial morbidity due to encasement of, or close proximity to, vital structures, invasiveness, or high vascularity of the PN.
- A PN is defined as a neurofibroma that has grown along the length of a nerve and may involve multiple fascicles and branches. A spinal PN involves two or more levels with connection between the levels or extending laterally along the nerve.
- In addition to PN, subjects must have at least 1 other diagnostic criterion for NF1 as follows:
Key exclusion criteria (9 listed)
- Evidence of malignant peripheral nerve sheath tumour.
- Prior malignancy (except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, low grade optic pathway gliomas associated with NF1 which does not require systemic treatment or other cancer from which the subject had been disease free for ≥2 years or which would not have limited survival to <2 years) or other cancer requiring treatment with chemotherapy or radiation therapy.
- Clinically significant cardiovascular disease
- Known history of human immunodeficiency virus, serologic status reflecting active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, or any uncontrolled active systemic infection
- Subjects with clinically significant ophthalmological findings/conditions
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SelumetinibSelumetinib 25 mg/m2 BID | Drug | Selumetinib |
Primary outcome
Safety and tolerability in terms of adverse events
Time frame: From obtaining the first informed consent until 30 days after the last dose (Selumetinib). Expected duration is approximately 2 years.
Number of subjects with adverse events as a measure of safety and tolerability including changes in vital signs, electrocardiograms, safety laboratory parameters, echocardiogram and ophthalmologic assessment.
6 secondary outcomes
Maximum plasma concentration (Cmax)
Time frame: From obtaining the first informed consent until 30 days after the last dose (Selumetinib). Expected duration is approximately two years.
Area under the plasma concentration-time curve (AUC)
Time frame: From obtaining the first informed consent until 30 days after the last dose (Selumetinib). Expected duration is approximately two years.
Overall response rate
Time frame: Assessed at every 4 cycles until drug permanently discontinued. Expected duration is approximately 2 years. Each cycle is 28 days.
Duration of response
Time frame: Assessed at every 4 cycles until drug permanently discontinued. Expected duration is approximately 2 years. Each cycle is 28 days.
Clinical Global Impression of Change (CGIC)
Time frame: Assessed at every 2 cycles for the first year and every 4 cycles until drug permanently discontinued. Expected duration is approximately 2 years. Each cycle is 28 days.
Total scale score of Paediatric Quality of Life Inventory (PedsQL; self- and parent-reported)
Time frame: Assessed at every 4 cycles until drug permanently discontinued. Expected duration is approximately 2 years. Each cycle is 28 days.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Apr 2023.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Related trials for Neurofibromatosis Type 1
RecruitingObservational study
Development and Validation of Patient Reported Outcome (PRO) Measures for Individuals With Neurofibromatosis 1 (NF1) and Plexiform Neurofibromas (pNFs)
Neurofibromatosis 1, Plexiform Neurofibromas
RecruitingPhase 1
Phase I Trial of TURALIO(R) (Pexidartinib, PLX3397) in Children and Young Adults With Refractory Leukemias and Refractory Solid Tumors Including Neurofibromatosis Type 1 (NF1) Associated Plexiform Neurofibromas (PN) and Tenosynovial Giant Cell Tumor ...
Neurofibroma, Plexiform, Precursor Cell Lymphoblastic Leukemia-Lymphoma
RecruitingPhase 3
A Study of the Drugs Selumetinib vs. Carboplatin and Vincristine in Patients With Low-Grade Glioma
Low Grade Astrocytoma, Low Grade Glioma
RecruitingPhase 1
PAS-004 in Adults Who Have Neurofibromatosis Type 1 With Plexiform Neurofibromas
NF1 Mutation, Neurofibroma Plexiform
Not yet recruitingPhase 2
Selumetinib for NF2-Related Schwannomatosis
Neurofibromatosis Type 2, NF2
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Selumetinib in people with Neurofibromatosis Type 1, run by AstraZeneca at 3 sites in Japan.
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 13 inclusion and 9 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: finished, as of the sponsor's last update on 26 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Japan. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Safety and tolerability in terms of adverse events (time frame: From obtaining the first informed consent until 30 days after the last dose (Selumetinib). Expected duration is approximately 2 years.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 26 Apr 2023.