Selumetinib in Treating Patients With Neurofibromatosis Type 1 and Cutaneous Neurofibroma
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02839720|
Recruitment Status : Recruiting
First Posted : July 21, 2016
Last Update Posted : January 23, 2020
|Condition or disease||Intervention/treatment||Phase|
|Cutaneous Neurofibroma Neurofibromatosis Type 1 Optic Nerve Glioma||Other: Laboratory Biomarker Analysis Drug: Selumetinib Drug: Selumetinib Sulfate||Phase 2|
I. Determine if selumetinib can result in shrinkage of cutaneous neurofibromas.
I. Assess the effect of selumetinib on target inhibition in cutaneous neurofibroma(s) excised prior treatment and on treatment with selumetinib for analysis of percent inhibition of phosphorylated ERK (pERK), and changes in phosphorylated AKT (pAKT).
I. Assess the effect of selumetinib on the development on new cutaneous neurofibromas while on treatment with selumetinib.
II. Assess the effect of selumetinib on target inhibition in cutaneous neurofibroma(s) excised prior treatment and on treatment with selumetinib for analysis of the tumor kinome.
III. Assess the effect of selumetinib skin related morbidity and pain using the Skindex, the Global Impression of Change Scale and Numeric Rating Scale, all of which are patient reported outcome measures.
IV. Quantify the development of new cutaneous neurofibromas on treatment with selumetinib.
V. Detailed pathologic analysis of cutaneous neurofibromas pretreatment and on treatment with selumetinib for changes in cell composition (including macrophage and mast cell infiltration).
VI. Investigate alterations that correlate with cutaneous neurofibroma (cNF) response to selumetinib treatment with pilot genomic, deoxyribonucleic acid (DNA) methylation, and transcriptomic studies.
Patients receive selumetinib orally (PO) twice daily (BID) on days 1-28. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients who experience a volume decrease in the target cutaneous neurofibromas may continue treatment for 12 additional cycles.
After completion of study treatment, patients are followed up every 4 months for 1 year.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||24 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Pilot Study of the MEK1/2 Inhibitor Selumetinib (AZD6244 Hydrogen Sulfate) for Adults With Neurofibromatosis Type 1 (NF1) and Cutaneous Neurofibromas (CNF)|
|Actual Study Start Date :||April 11, 2017|
|Estimated Primary Completion Date :||December 31, 2021|
|Estimated Study Completion Date :||December 31, 2021|
Experimental: Treatment (selumetinib)
Patients receive selumetinib PO BID on days 1-28. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients who experience a volume decrease in the target cutaneous neurofibromas may continue treatment for 12 additional cycles.
Other: Laboratory Biomarker Analysis
Drug: Selumetinib Sulfate
- Change in the size of neurofibromatosis type 1 (NF1) tumors and cutaneous neurofibromas assessed by digital photography [ Time Frame: Baseline to up to 1 year ]The width, length, and height will be measured, and the volume of each of the neurofibromas measured will be calculated. The effect of selumetinib will be separately evaluated 3-5 small (longest neurofibroma diameter 3-7 mm) and 3-5 larger (longest neurofibroma diameter >= 8 mm) neurofibromas in each of the 3 regions. The sum of the on-treatment volumes for the smaller tumors will be subtracted from the pre-treatment volumes of the same tumors to arrive at an overall percentage change in tumor size for each patient. This will be repeated for the larger tumors. Then, the average percentage change for each size category will be reported along with its 95% confidence interval, and other associated statistics.
- Change in the number of neurofibromas [ Time Frame: Baseline to up to 1 year ]At the time of each response evaluation the number of neurofibromas will be counted in the picture frames, and the volume of the target neurofibromas will be measured.
- Incidence of toxicity [ Time Frame: Up to 1 year ]Will be summarized descriptively and tabulations on the type, severity, and relationship to study treatment will be performed.
- Changes in skin related morbidity [ Time Frame: Baseline to up to 1 year ]Assessed by Skindex, Global Impression of Change Scale, and Numeric Rating Scale evaluations. May be compared to changes in average volume for tumors of a given size. Will be summarized using descriptive statistics and when feasible compared using Wilcoxon rank test or pairwise t-test.
- Changes in pathway biomarkers assessed by kinome analysis [ Time Frame: Baseline to up to 1 year ]Will be tested for statistical significance using a Wilcoxon signed rank test.
- Changes in levels of pERK and pAKT assessed by quantitative enzyme-linked immunosorbent assay [ Time Frame: Baseline to up to 1 year ]Will be correlated with tumor volume changes using Spearman rank correlation. Exploratory comparisons between patients with a tumor response and those without a response will be done using a Wilcoxon rank sum test.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02839720
|United States, Alabama|
|University of Alabama at Birmingham Cancer Center||Recruiting|
|Birmingham, Alabama, United States, 35233|
|Contact: Bruce R. Korf 205-934-9411 email@example.com|
|Principal Investigator: Bruce R. Korf|
|United States, Maryland|
|National Institutes of Health Clinical Center||Not yet recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: Brigitte C. Widemann 240-760-6203 firstname.lastname@example.org|
|Principal Investigator: Brigitte C. Widemann|
|United States, Texas|
|UT Southwestern/Simmons Cancer Center-Dallas||Not yet recruiting|
|Dallas, Texas, United States, 75390|
|Contact: Lu Q. Le 214-648-7097 email@example.com|
|Principal Investigator: Lu Q. Le|
|Principal Investigator:||Bruce R Korf||University of Alabama at Birmingham Cancer Center|