Neurofibromatosis 1Phase 2plexifpcNCT03741101
Treatment of NF1-related Plexiform Neurofibroma With Trametinib
A Phase 2 study testing Trametinib in people with Neurofibromatosis 1 and Child, run by Region Skane at 1 site in Sweden.
Trial summary
This trial, Treatment of NF1-related plexiform neurofibroma with trametinib; a single arm,open-label study with the goals of volumetric partial remission and pain relief (EudraCT 2018-001846-32, Sponsor protocol number BUS2018-1, related Novartis reference number CTMT212ASE01T) is a pediatric clinical trial that… Read more about this study
- Who is it for?
- Ages 1 year to 17 years
- Conditions the study is for
- Neurofibromatosis 1, Child, Neurofibroma, Plexiform
- What is being tested?
- Trametinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteSweden
- Study dates
- 10 Jun 2019to 15 Dec 2024
- Phase
- Phase 2
- 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 1 year to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- NF1-related PN with severe - or with high suspicion of becoming severe - manifestations
- Informed consent provided
- Age 1:0-17:11
Who cannot join
- NF1-related PN does not fulfill characteristics for acceptable volumetric MRI assessments as outlined under Criteria for volumetric assessment.
- Lactating or pregnant females. Sexually active females, who do not (agree to) use safe contraception or adhere to regular controls during study. Sexually active males who do not (agree to) use a condom during coitus.
- A history of other malignancies than classic NF1-related WHO grade 1 tumors (i.e. PN or optic pathway glioma).
- A history of NF-1 related cerebral vascular anomalies (such as Moyamoya).
- Active pharmaceutical therapy for optic pathway malignancy/ies.
- Any medication for treatment of left ventricular systolic dysfunction.
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- Use of any investigational drug within 30 days of the first dose of this study treatment.
- Impaired renal function (GFR under 45 ml/min/1,73m2 - It is only required to analyze eGFR if creatine is above institutional reference value for corresponding age group).
- A known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study drug or excipients that contraindicate their participation.
- Active liver or biliary disease or moderate or severe liver impairment. If there are signs of liver disease (such as an increased prothrombin time or elevated transaminases),grading of the liver impairment has to be done in consultation with a hepatologist, since there is no universal definition.
- A history of hepatic sinusoid obstructive syndrome (venoocclusive disease) within the last 3 months.
- A history of heparin-induced thrombocytopenia.
- A history of interstitial lung disease or pneumonitis.
- A history of retinal vein occlusion (RVO).
- A history of Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection. Subjects with a confirmed cleared HBV and HCV infection may be enrolled.
- Presence of a condition that will interfere significantly with the absorption of drugs.
- Evidence of cardiovascular risk, such as left ventricular ejection fraction (LVEF) below the lower limit of normal (LLN), a corrected QT-interval (Qtc) >480 milliseconds, clinically significant uncontrolled arrhythmia, congestive heart failure, or acute coronary syndrome or history thereof.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Treatment of NF1-related Plexiform Neurofibroma With Trametinib; a Single Arm, Open-label Trial With the Goals of Volumetric Partial Remission and Pain Relief
This trial, Treatment of NF1-related plexiform neurofibroma with trametinib; a single arm,open-label study with the goals of volumetric partial remission and pain relief (EudraCT 2018-001846-32, Sponsor protocol number BUS2018-1, related Novartis reference number CTMT212ASE01T) is a pediatric clinical trial that investigates the potential use of the drug trametinib (Mekinist®) as treatment for symptomatic or likely to become symptomatic NF1-related plexiform neurofibromas (PN) in children between 1 year and 17 year and 11 months of age.
Trametinib is orally administered qd at 0.025 mg/kg up to a maximum of 2 mg from six years of age and 0.032mg/kilo up to 5 years of age, provided either as tablets or as oral solution. It is manufactured and distributed by Novartis under the trade name Mekinist®.
Read more
The primary endpoint is remission of tumor volume ≥20%, evaluated using volumetric MRI at 18 and 30 months of treatment.
The secondary endpoint is reversal of pain from NF1-related PN, evaluated monthly with agespecific pain scales; VAS scale (from 8 years) or Faces Pain Scale (from 3 to 8 years).
As an exploratory measure, the potential effects of the treatment on the cognitive function will be assessed using well-established tests such as WISC-V (age range 6:0 - 16:11), NEPSY-II (age range 3:0-16:11), and CPT-3 (age range 8:0 - adult).
Cognitive dysfunction is well described in patients with NF1, and the MAPK/ERK-pathway has been indicated to be involved in cognition.
- Conditions
- Neurofibromatosis 1, Child, Neurofibroma, Plexiform
- Being tested
- Trametinib
- Medical subject headings
- Neurofibromatosis 1, Neurofibroma, Plexiform
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TrametinibDrug
Also called mekinist
treatment
| Study group | Role | What they receive |
|---|---|---|
| single arm study | Experimental | children treated with trametinib Receives: Drug: Trametinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Remission of tumor volume ≥20%
Final and primary analysis of primary outcome measure - of pooled data at 30 months (end of study) with volumetric mri of tumor volume versus volume at enrolment.
Measured: 0 - 30 months.
Remission of tumor volume ≥20%
Interim analysis of pooled data at 18 months with volumetric mri of tumor volume versus volume at enrolment. This is an interim analysis of primary outcome and not primary analysis of primary outcome".
Measured: 0 - 18 months
Secondary outcomes (2)
Reversal of NF1-related PN elicited - VAS scale pain
Evaluated with monthly VAS pain scale from 8 years at enrolment. Monthly. 0-10 point scale. Descriptive. Analysis of pooled data after month 30.
Measured: 0 - 30 months.
Reversal of NF1-related PN elicited pain - Faces Pain Scale
Evaluated with monthly Faces Pain Scale from under 8 years at enrolment. Monthly. 0-10 scale. Descriptive. Analysis of pooled data after month 30.
Measured: 0 - 30 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Nov 2018
- Study start10 Jun 2019
- Primary completion15 Jul 2024 (estimated)
- Study completion15 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neurofibromatosis 1Studies of the same condition, open and under way.
- More trials run by Region SkaneThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Region Skane
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor
- Investigators
- Björn Sigurdsson, Principal investigator, Skane University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03741101
- Sponsor's protocol ID
- BUS2018-1
- Other IDs
- 2018-001846-32, 2018
- Acronym
- plexifpc
- Status last verified
- Apr 2024
- First submitted
- 5 Nov 2018
- Last updated
- 11 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of NF1-related Plexiform Neurofibroma With Trametinib; a Single Arm, Open-label Trial With the Goals of Volumetric Partial Remission and Pain Relief
- ClinicalTrials.gov ID
- NCT03741101
- Acronym / sponsor ID
- plexifpc / BUS2018-1
- Conditions
- Neurofibromatosis 1, Child, Neurofibroma, Plexiform
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Region SkaneUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- 10 Jun 2019 (actual)
- Primary completion
- 15 Jul 2024 (estimated)
- Study completion
- 15 Dec 2024 (estimated)
- First posted
- 14 Nov 2018 (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 trial, Treatment of NF1-related plexiform neurofibroma with trametinib; a single arm,open-label study with the goals of volumetric partial remission and pain relief (EudraCT 2018-001846-32, Sponsor protocol number BUS2018-1, related Novartis reference number CTMT212ASE01T) is a pediatric clinical trial that investigates the potential use of the drug trametinib (Mekinist®) as treatment for symptomatic or likely to become symptomatic NF1-related plexiform neurofibromas (PN) in children between 1 year and 17 year and 11 months of age.
Trametinib is orally administered qd at 0.025 mg/kg up to a maximum of 2 mg from six years of age and 0.032mg/kilo up to 5 years of age, provided either as tablets or as oral solution. It is manufactured and distributed by Novartis under the trade name Mekinist®.
The primary endpoint is remission of tumor volume ≥20%, evaluated using volumetric MRI at 18 and 30 months of treatment.
The secondary endpoint is reversal of pain from NF1-related PN, evaluated monthly with agespecific pain scales; VAS scale (from 8 years) or Faces Pain Scale (from 3 to 8 years).
As an exploratory measure, the potential effects of the treatment on the cognitive function will be assessed using well-established tests such as WISC-V (age range 6:0 - 16:11), NEPSY-II (age range 3:0-16:11), and CPT-3 (age range 8:0 - adult).
Cognitive dysfunction is well described in patients with NF1, and the MAPK/ERK-pathway has been indicated to be involved in cognition.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| single arm study | Experimental | Drug: Trametinibchildren treated with trametinib |
Who may qualify
- Ages
- 1 year to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- NF1-related PN with severe - or with high suspicion of becoming severe - manifestations
- Informed consent provided
- Age 1:0-17:11
Key exclusion criteria (17 listed)
- NF1-related PN does not fulfill characteristics for acceptable volumetric MRI assessments as outlined under Criteria for volumetric assessment.
- Lactating or pregnant females. Sexually active females, who do not (agree to) use safe contraception or adhere to regular controls during study. Sexually active males who do not (agree to) use a condom during coitus.
- A history of other malignancies than classic NF1-related WHO grade 1 tumors (i.e. PN or optic pathway glioma).
- A history of NF-1 related cerebral vascular anomalies (such as Moyamoya).
- Active pharmaceutical therapy for optic pathway malignancy/ies.
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 |
|---|---|---|
| TrametinibAlso: mekinisttreatment | Drug | single arm study |
Primary outcome
Remission of tumor volume ≥20%
Time frame: 0 - 30 months.
Final and primary analysis of primary outcome measure - of pooled data at 30 months (end of study) with volumetric mri of tumor volume versus volume at enrolment.
Remission of tumor volume ≥20%
Time frame: 0 - 18 months
Interim analysis of pooled data at 18 months with volumetric mri of tumor volume versus volume at enrolment. This is an interim analysis of primary outcome and not primary analysis of primary outcome".
2 secondary outcomes
Reversal of NF1-related PN elicited - VAS scale pain
Time frame: 0 - 30 months.
Reversal of NF1-related PN elicited pain - Faces Pain Scale
Time frame: 0 - 30 months.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Apr 2024.
- clinical trial register EULink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Björn Sigurdsson principal investigator
Skane University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Trametinib in people with Neurofibromatosis 1 and Child, run by Region Skane at 1 site in Sweden.
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 3 inclusion and 17 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: status not confirmed, as of the sponsor's last update on 11 Apr 2024. 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 Sweden. 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?
Results are not available in the source record.
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?
Remission of tumor volume ≥20% (time frame: 0 - 30 months.). 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?
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 11 Apr 2024.