Systematically Assessing Changes in Plexiform Neurofibroma Related Disfigurement From Photographs of Subjects With Neurofibromatosis Type 1 on a Phase 2 Clinical Trial

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....

Study Overview

• Status: Completed
• Conditions: Neurofibromatosis 1

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 Type: Observational
• Enrollment (Actual): 52

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health Clinical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

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

Description

• INCLUSION CRITERIA:
• 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.

EXCLUSION CRITERIA:

• 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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort
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 the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	ongoing

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	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	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	ongoing
Factors most important in causing change in disfigurement	descriptive statistical analysis of factors	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.	ongoing
Feasibility of understanding and completing a novel disfigurement scale	descriptive findings of questionnaire responses	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	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	ongoing

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Andrea M Gross, M.D., National Cancer Institute (NCI)

Publications and helpful links

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): May 12, 2021
• Primary Completion (Actual): August 15, 2022
• Study Completion (Actual): August 15, 2022

Study Registration Dates

• First Submitted: May 7, 2021
• First Submitted That Met QC Criteria: May 7, 2021
• First Posted (Actual): May 10, 2021

Study Record Updates

• Last Update Posted (Actual): March 22, 2024
• Last Update Submitted That Met QC Criteria: March 20, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Natural History; Selumetinib; novel disfigurement scale
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Genetic Diseases, Inborn; Neuromuscular Diseases; Neurodegenerative Diseases; Neoplasms, Nerve Tissue; Peripheral Nervous System Diseases; Nervous System Neoplasms; Heredodegenerative Disorders, Nervous System; Neoplastic Syndromes, Hereditary; Nerve Sheath Neoplasms; Neurocutaneous Syndromes; Peripheral Nervous System Neoplasms; Neurofibromatoses; Neurofibromatosis 1; Neurofibroma; Neurofibroma, Plexiform
• Other Study ID Numbers: 10000173; 000173-C

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: .All IPD recorded in the medical record will be shared with intramural investigators upon request.
• IPD Sharing Time Frame: Clinical data available during the study and indefinitely.
• IPD Sharing Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No