Efficacy and Safety of Selumetinib in Adults with NF1 who have Symptomatic, Inoperable Plexiform Neurofibromas
- Conditions
- eurofibromatosis Type 1 (NF1) with Symptomatic, Inoperable Plexiform Neurofibromas (PN)MedDRA version: 20.0Level: LLTClassification code 10029270Term: Neurofibromatosis, type 1 (von Recklinghausen's disease)System Organ Class: 100000004850Therapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2020-005607-39-IT
- Lead Sponsor
- ASTRAZENECA AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 146
- Adults = 18 years at enrollment with diagnosis of NF1 with symptomatic, inoperable PN
- At least one target PN measurable by volumetric MRI analysis
- Chronic target PN pain score documented for minimum period during screening period
- Stable chronic PN pain medication use at enrollment
- Adequate organ and marrow function
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 139
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 7
- Confirmed or suspected malignant glioma or MPNST (optic glioma not requiring chemotherapy or radiation therapy are exempt from this exclusion)
- History of malignancy except for malignancy treated with curative intent with no known active disease = 5 years before the first dose of study intervention and of low potential risk for recurrence
- Clinically significant cardiovascular disease, including inherited coronary disease, acute coronary syndrome within 6 months prior to enrollment, uncontrolled angina, symptomatic heart failure,
cardiomyopathy, severe valvular heart disease, abnormal LVEF and uncontrolled hypertension
- Ophthalmological findings/conditions including intraocular pressure > 21 mmHg, RPED/CSR or RVO
- Prior exposure to MEK inhibitors
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To demonstrate the effectiveness of Selumetinib by assessment of ORR in participants with NF1 who have symptomatic, inoperable PN;Secondary Objective: - To compare the effect of selumetinib relative to placebo by assessment of chronic target PN pain intensity<br>- To demonstrate the effectiveness of selumetinib alone and as compared to placebo by assessment of additional tumour response variables, chronic target PN pain palliation, pain medication use, pain interference, physical functioning, HRQoL and health status<br>- To assess the safety and tolerability of selumetinib alone and as compared to placebo<br>- To assess the PK of selumetinib;Primary end point(s): Objective Response Rate (ORR) using volumetric MRI analysis as determined by ICR per REiNS criteria;Timepoint(s) of evaluation of this end point: Assessments for ORR will be collected regularly at predefined time points until disease progression
- Secondary Outcome Measures
Name Time Method Secondary end point(s): - Change from baseline in chronic target PN pain intensity<br>- Duration of Response (DoR)<br>- Progression Free Survival (PFS)<br>- Time to progression (TTP)<br>- Time to Response (TTR)<br>- Best percentage change from baseline in target PN volume<br>- Pain palliation, pain medication use, pain interference, physical functioning, health related quality of life PROs and health status.<br>- Safety and tolerability<br>- Plasma concentrations and PK parameters of selumetinib and Ndesmethyl selumetinib;Timepoint(s) of evaluation of this end point: Assessments will be made regularly until disease progression or until the end of the study