Neurofibromatosis 1NCT04879160
Systematically Assessing Changes in Plexiform Neurofibroma Related Disfigurement From Photographs of Subjects With Neurofibromatosis Type 1 on a Phase 2 Clinical Trial
An observational study of Neurofibromatosis 1, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Background: People with Neurofibromatosis type 1 (NF1) have an increased risk of developing plexiform neurofibromas (PNs). PNs are tumors that form in the tissue. They can form anywhere in the body. They can become visible and cause deformations. Read more about this study
- Who is it for?
- Ages 7 years and olderHealthy volunteers can take part
- Conditions the study is for
- Neurofibromatosis 1
- How many people
- 52 participants
- Where
- 1 siteUnited States
- Study dates
- 12 May 2021to 15 Aug 2022
- Phase
- Observational
- 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 7 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: Clinicians and non-clinician raters familiar with NF1; Participants enrolled on NIH protocols 11-C-0161 and 08-C-0079 with NF1 and visible plexiform neurofibromas
Who may be able to join
- Clinician Raters - those who are professionally involved with direct patient care and have a career in the medical field and familiar with NF1 (Cohort 1A), OR
- Clinician Raters - those who are professionally involved with direct patient care and have a career in the medical field but are not familiar with NF1 (Cohort 1B), OR
- Non-clinician Raters - those who are not professionally involved in direct patient care or do not have a career in the medical field, but who are a first or second degree relative of a subject with NF1 or are otherwise closely associated with a subject with NF1 and familiar with NF1 (Cohort 2A), OR
- Non-clinician Raters - those who are not professionally involved in direct patient care or do not have a career in the medical field, and who are not a first or second degree relative of a subject with NF1 and are otherwise not closely associated with a subject with NF1 (Cohort 2B)
- Age greater than or equal to18 years.
- The ability of a subject to understand and the willingness to sign a written informed consent document.
- Ability to read and write in English.
Who cannot join
- Raters should not be employees of the NIH.
- Raters should not be directly involved in the NCI Phase 1/2 study of selumetinib (11-C-0161), either as an investigator or as a subject or first-degree family member of a subject enrolled on the trial.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Background:
People with Neurofibromatosis type 1 (NF1) have an increased risk of developing plexiform neurofibromas (PNs). PNs are tumors that form in the tissue. They can form anywhere in the body. They can become visible and cause deformations. Researchers want to see if selumetinib changes how PNs look in people with NF1. They also want to test a rating system for the visibility of these tumors.
Read more
Objective:
To see if treatment with selumetinib can improve the appearance of visible PNs in people with NF1, as determined by people who are/are not familiar with NF1.
Eligibility:
People with NF1 who have one or more visible PNs and have been enrolled in study 11C0161 or 08C0079. Clinicians and non-clinicians with and without experience in NF1 are also needed to serve as raters.
Design:
Participants are people with NF1 who had photos taken on study 11C0161 or 08C0079. Raters are people who will evaluate the PNs in the photos. They will rate the tumors on a scale from 1 to 10, from less to most visible.
Participants medical records will be reviewed. Their photos will be shown to 28 raters.
Raters will fill out a survey about their demographics, place of work, and if they are familiar with NF1. They will view sample photos to learn how PNs look and how to rate PNs.
Raters will view photos of PNs taken before and after selumetinib treatment. They will also view photos of PNs that were not treated. They will rate PNs for up to 40 participants. They will have 1-2 sessions. Each session will last 1 hour....
Read the detailed description
Background:
Up to 50% of subjects with Neurofibromatosis Type 1 (NF1) will develop histologically benign plexiform neurofibromas (PN).
One of the most common morbidities associated with PN is a disfigurement that has the potential to pose formidable obstacles to the medical and psychosocial well-being of subjects with NF1.
The phase 2 trial of the MEK inhibitor selumetinib for inoperable PN (NCT01362803) have shown volumetric shrinkage of PN in approximately 74% of subjects with at least one PN morbidity, with most of the responsive tumors decreasing in size by 20-50% volume from baseline. Both trials have completed enrollment and primary study objectives.
In this selumetinib trial, standardized photography of visible PN was performed over time to assess for changes in disfigurement over time. This trial did not include criteria to measure changes in disfigurement and no validated criteria for measurement of PN-related disfigurement exist.
We developed a scale to rate the extent of a disfigurement from NF1 PN and will apply this scale to photographs obtained on the phase II selumetinib trial.
Objective:
To determine if selumetinib treatment is associated with improvement in PN-related disfigurement, as determined by raters reviewing photographs before treatment and just prior to cycle 13 of treatment.
Eligibility:
Four groups of adult raters to rate disfigurement who are not directly involved in the conduct of the selumetinib treatment study (NCT01362803), who are not NIH employees, and can read and write in English.
Design:
-Methods
Photographs of consenting individuals with PN, who may or may not have received selumetinib will be reviewed.
Raters will be presented pre and post treatment photographs of persons who received selumetinib as well as control photographs of persons not receiving selumetinib.
Each rater is presented with the same set of photographs though placement and order may differ.
Each rater will look at photographs of each individual with PN for at least 10 seconds, then with photos still visible, raters will verbally answer a questionnaire.
The rater will be asked questions at the end of the session to assess the feasibility of the questionnaire.
Session will be repeated by some raters approximately six months later on a subset of the photographs.
-Statistical Analysis
In each cohort of raters, for each subject s slide set evaluated at a time point, the mean of the raters scores for each subject will be formed.
For each person with PN that received selumetinib, the paired difference between baseline and pre-cycle 13 of these mean scores will be determined.
For the full set of approximately 35 paired scores, the difference will be assessed for statistical importance by means of a paired t-test, or a Wilcoxon signed rank test.
- Conditions
- Neurofibromatosis 1
- Keywords
- Selumetinib, novel disfigurement scale, Natural History
- Medical subject headings
- Neurofibromatosis 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 1/ Cohort 1A | Clinician raters familiar with NF1 | |
| 2/ Cohort 1B | Clinician raters without specific NF1 familiarity | |
| 3/ Cohort 2A | Non-clinician raters familiar with NF1 | |
| 4/ Cohort 2B | Non-clinician raters without specific NF1 familiarity | |
| 5/ Cohort 3 | Subjects with NF1 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluation of the degree of changes in disfigurement measures
Mean scores for disfigurement as determined by raters reviewing photographs before treatment and just prior to cycle 13 of treatment.
Measured: ongoing
Secondary outcomes (9)
Differences in the disfigurement scores assigned by raters between cohorts of clinical raters who differ by NF1 familiarity and non-clinical raters who differ by NF1 familiarity
mean scores for disfigurement will be compared using a paired t-test or Wilcoxon signed rank test
Measured: ongoing
Correlation between achieving a partial response on selumetinib and having an improvement in PN-related disfigurement
changes in score will be compared using a Wilcoxon rank sum test
Measured: ongoing
Intra-reliability of a novel disfigurement scale among raters
scores for disfigurement at initial evaluation and a subsequent evaluation to assess reliability will be obtained and subtracted to form the difference in each score at the two time points
Measured: ongoing
Correlation between the degree of change in disfigurement and percentage of PN volume shrinkage
Spearman correlation analysis to assess the degree of change in disfigurement and percentage of PN volume shrinkage from baseline
Measured: ongoing
Factors most important in causing change in disfigurement
descriptive statistical analysis of factors
Measured: ongoing
Agreement among raters within a cohort with respect to the evaluation of disfigurement to assess the reliability of a novel disfigurement scale
Full set of 15 pairwise Kappa statistics, taken two at a time will be constructed. For the full set of 15 Kappa statistics, the mean value along with a two-sided 95% confidence interval, will be reported separately for each of the 4 cohorts.
Measured: ongoing
Feasibility of understanding and completing a novel disfigurement scale
descriptive findings of questionnaire responses
Measured: ongoing
Overall difference among the 4 cohorts of raters with respect to scores assigned for disfigurement
mean scores for disfigurement will be compared using ANOVA or Kruskal-Wallis test as appropriate
Measured: ongoing
PN-related disfigurement rating consistency with subject/parent responses to Global Impression of Change (GIC)
descriptive findings of ratings compared to Global Impression of Change (GIC) responses
Measured: ongoing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2021
- Study start12 May 2021
- Primary completion15 Aug 2022
- Study completion15 Aug 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Neurofibromatosis 1Studies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Andrea M Gross, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04879160
- Sponsor's protocol ID
- 10000173
- Other IDs
- 000173-C
- Status last verified
- Mar 2024
- First submitted
- 7 May 2021
- Last updated
- 22 Mar 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: .All IPD recorded in the medical record will be shared with intramural investigators upon request.
Publications
John L, Singh G, Dombi E, Wolters PL, Martin S, Baldwin A, Steinberg SM, Bernstein J, Whitcomb P, Pichard DC, Dufek A, Gillespie A, Heisey K, Bornhorst M, Fisher MJ, Weiss BD, Kim A, Widemann BC, Gross AM. Development and pilot validation of a novel disfigurement severity scale for plexiform neurofibromas in children with neurofibromatosis type 1. Clin Trials. 2024 Apr;21(2):189-198. doi: 10.1177/17407745231206402. Epub 2023 Oct 25.
PubMed 37877369
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Systematically Assessing Changes in Plexiform Neurofibroma Related Disfigurement From Photographs of Subjects With Neurofibromatosis Type 1 on a Phase 2 Clinical Trial
- ClinicalTrials.gov ID
- NCT04879160
- Acronym / sponsor ID
- 10000173
- Conditions
- Neurofibromatosis 1
- Keywords
- Selumetinib, novel disfigurement scale, Natural History
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 12 May 2021 (actual)
- Primary completion
- 15 Aug 2022 (actual)
- Study completion
- 15 Aug 2022 (actual)
- First posted
- 10 May 2021 (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.
Background:
People with Neurofibromatosis type 1 (NF1) have an increased risk of developing plexiform neurofibromas (PNs). PNs are tumors that form in the tissue. They can form anywhere in the body. They can become visible and cause deformations. Researchers want to see if selumetinib changes how PNs look in people with NF1. They also want to test a rating system for the visibility of these tumors.
Objective:
To see if treatment with selumetinib can improve the appearance of visible PNs in people with NF1, as determined by people who are/are not familiar with NF1.
Eligibility:
People with NF1 who have one or more visible PNs and have been enrolled in study 11C0161 or 08C0079. Clinicians and non-clinicians with and without experience in NF1 are also needed to serve as raters.
Design:
Participants are people with NF1 who had photos taken on study 11C0161 or 08C0079. Raters are people who will evaluate the PNs in the photos. They will rate the tumors on a scale from 1 to 10, from less to most visible.
Participants medical records will be reviewed. Their photos will be shown to 28 raters.
Raters will fill out a survey about their demographics, place of work, and if they are familiar with NF1. They will view sample photos to learn how PNs look and how to rate PNs.
Raters will view photos of PNs taken before and after selumetinib treatment. They will also view photos of PNs that were not treated. They will rate PNs for up to 40 participants. They will have 1-2 sessions. Each session will last 1 hour....
Detailed description
Background:
Up to 50% of subjects with Neurofibromatosis Type 1 (NF1) will develop histologically benign plexiform neurofibromas (PN).
One of the most common morbidities associated with PN is a disfigurement that has the potential to pose formidable obstacles to the medical and psychosocial well-being of subjects with NF1.
The phase 2 trial of the MEK inhibitor selumetinib for inoperable PN (NCT01362803) have shown volumetric shrinkage of PN in approximately 74% of subjects with at least one PN morbidity, with most of the responsive tumors decreasing in size by 20-50% volume from baseline. Both trials have completed enrollment and primary study objectives.
In this selumetinib trial, standardized photography of visible PN was performed over time to assess for changes in disfigurement over time. This trial did not include criteria to measure changes in disfigurement and no validated criteria for measurement of PN-related disfigurement exist.
We developed a scale to rate the extent of a disfigurement from NF1 PN and will apply this scale to photographs obtained on the phase II selumetinib trial.
Objective:
To determine if selumetinib treatment is associated with improvement in PN-related disfigurement, as determined by raters reviewing photographs before treatment and just prior to cycle 13 of treatment.
Eligibility:
Four groups of adult raters to rate disfigurement who are not directly involved in the conduct of the selumetinib treatment study (NCT01362803), who are not NIH employees, and can read and write in English.
Design:
-Methods
Photographs of consenting individuals with PN, who may or may not have received selumetinib will be reviewed.
Raters will be presented pre and post treatment photographs of persons who received selumetinib as well as control photographs of persons not receiving selumetinib.
Each rater is presented with the same set of photographs though placement and order may differ.
Each rater will look at photographs of each individual with PN for at least 10 seconds, then with photos still visible, raters will verbally answer a questionnaire.
The rater will be asked questions at the end of the session to assess the feasibility of the questionnaire.
Session will be repeated by some raters approximately six months later on a subset of the photographs.
-Statistical Analysis
In each cohort of raters, for each subject s slide set evaluated at a time point, the mean of the raters scores for each subject will be formed.
For each person with PN that received selumetinib, the paired difference between baseline and pre-cycle 13 of these mean scores will be determined.
For the full set of approximately 35 paired scores, the difference will be assessed for statistical importance by means of a paired t-test, or a Wilcoxon signed rank test.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| 1/ Cohort 1A | – | –Clinician raters familiar with NF1 |
| 2/ Cohort 1B | – | –Clinician raters without specific NF1 familiarity |
| 3/ Cohort 2A | – | –Non-clinician raters familiar with NF1 |
| 4/ Cohort 2B | – | –Non-clinician raters without specific NF1 familiarity |
| 5/ Cohort 3 | – | –Subjects with NF1 |
Who may qualify
- Ages
- 7 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Clinicians and non-clinician raters familiar with NF1; Participants enrolled on NIH protocols 11-C-0161 and 08-C-0079 with NF1 and visible plexiform neurofibromas
Key inclusion criteria (7 listed)
- Clinician Raters - those who are professionally involved with direct patient care and have a career in the medical field and familiar with NF1 (Cohort 1A), OR
- Clinician Raters - those who are professionally involved with direct patient care and have a career in the medical field but are not familiar with NF1 (Cohort 1B), OR
- Non-clinician Raters - those who are not professionally involved in direct patient care or do not have a career in the medical field, but who are a first or second degree relative of a subject with NF1 or are otherwise closely associated with a subject with NF1 and familiar with NF1 (Cohort 2A), OR
- Non-clinician Raters - those who are not professionally involved in direct patient care or do not have a career in the medical field, and who are not a first or second degree relative of a subject with NF1 and are otherwise not closely associated with a subject with NF1 (Cohort 2B)
- Age greater than or equal to18 years.
Key exclusion criteria (2 listed)
- Raters should not be employees of the NIH.
- Raters should not be directly involved in the NCI Phase 1/2 study of selumetinib (11-C-0161), either as an investigator or as a subject or first-degree family member of a subject enrolled on the trial.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Evaluation of the degree of changes in disfigurement measures
Time frame: ongoing
Mean scores for disfigurement as determined by raters reviewing photographs before treatment and just prior to cycle 13 of treatment.
9 secondary outcomes
Differences in the disfigurement scores assigned by raters between cohorts of clinical raters who differ by NF1 familiarity and non-clinical raters who differ by NF1 familiarity
Time frame: ongoing
Correlation between achieving a partial response on selumetinib and having an improvement in PN-related disfigurement
Time frame: ongoing
Intra-reliability of a novel disfigurement scale among raters
Time frame: ongoing
Correlation between the degree of change in disfigurement and percentage of PN volume shrinkage
Time frame: ongoing
Factors most important in causing change in disfigurement
Time frame: ongoing
Agreement among raters within a cohort with respect to the evaluation of disfigurement to assess the reliability of a novel disfigurement scale
Time frame: ongoing
Feasibility of understanding and completing a novel disfigurement scale
Time frame: ongoing
Overall difference among the 4 cohorts of raters with respect to scores assigned for disfigurement
Time frame: ongoing
PN-related disfigurement rating consistency with subject/parent responses to Global Impression of Change (GIC)
Time frame: ongoing
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 22 Mar 2024.
- Derived from this study: PubMed 37877369John L, Singh G, Dombi E, Wolters PL, Martin S, Baldwin A, Steinberg SM, Bernstein J, Whitcomb P, Pichard DC, Dufek A, Gillespie A, Heisey K, Bornhorst M, Fisher MJ, Weiss BD, Kim A, Widemann BC, Gross AM. Development and pilot validation of a novel disfigurement severity scale for plexiform neurofibromas in children with neurofibromatosis type 1. Clin Trials. 2024 Apr;21(2):189-198. doi: 10.1177/17407745231206402. Epub 2023 Oct 25.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. .All IPD recorded in the medical record will be shared with intramural investigators upon request.
Related trials for Neurofibromatosis 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.
Andrea M Gross, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Neurofibromatosis 1, run by National Cancer Institute (NCI) 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 7 inclusion and 2 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 22 Mar 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 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.
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?
Evaluation of the degree of changes in disfigurement measures (time frame: ongoing). 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 NCT04879160, which also lists 1 linked publication.
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 Mar 2024.