Neurofibromatosis Type 1 (NF1) Related Plexiform Neurofibromas (PN) MedDRA version: 20.0 Level: LLT Classification code 10029270 Term: Neurofibromatosis, type 1 (von Recklinghausen's disease) System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Trade Name: Koselugo 10mg
Product Name: Selumetinib 10mg capsule
Product Code: AZD6244
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Selumetinib sulfate
CAS Number: 943332-08-9
Other descrip
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female participants aged = 12 to =65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1. Evidence or suspicion of optic glioma, malignant glioma, MPNST, or other cancer requiring treatment with chemotherapy or radiation therapy 2. Prior malignancy requiring active treatment (except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the participant had been disease free for = 2 years or which would not have limited survival to 1.5 × the ULN for age (with the exception of those with Gilbert syndrome) or AST/ALT > 2 × upper limit of normal. 6. Renal Function: Creatinine clearance or radioisotope glomerular filtration rate 1.2 mg/dL (for participants aged between 12 and 15 years) or > 1.5 mg/dL for participants aged > 15 years). 7. Participants with abnormal ophthalmological findings/conditions as listed in the protocol. 8. Have any unresolved chronic toxicity, associated with previous therapy for NF1-PN: - Gastrointestinal toxicity of CTCAE Grade 1 or higher. - Have any other unresolved chronic toxicity with CTCAE Grade = 2, except hair changes (such as alopecia or high lightening). 9. Participants who have previously been treated with a MEKi (including selumetinib) and either discontinued treatment or required a dose reduction due to toxicity 10. Have had recent major surgery within a minimum of 4 weeks prior to starting study intervention, with the exception of surgical placement for vascular access. Have planned major surgery during the treatment period. 11. Any multivitamin containing vitamin E must be stopped at least 7 days prior to initiation of selumetinib.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the effect of a low fat meal on the PK of selumetinib capsules after multiple doses at 25 mg/m2 [If T3 is conducted] To investigate the effect of a low fat meal on the PK of selumetinib capsules after multiple doses at the adjusted dose To investigate the GI toxicities of selumetinib capsules after multiple doses under fed conditions (T1 and T3) compared to fasted conditions (T2);Secondary Objective: To further assess the safety and tolerability of selumetinib capsules by assessment of all AEs, laboratory variables and vital signs To further evaluate the PK of selumetinib and N-desmethyl selumetinib metabolite after multiple doses under fed conditions, compared to fasted conditions;Primary end point(s): 1. Geometric mean ratio and 90% CI of selumetinib AUC0-12, SS for T1 (fed) versus T2 (fasted) 2. Geometric mean ratio and 90% CI of selumetinib AUC0-12, SS for T3 (fed) versus T2 (fasted) 3. Descriptive statistics for GI AEs graded by CTCAE Version 5.0; Gastrointestinal toxicity diary incorporating the mBSFS-C and Nausea and Vomiting Symptom Rating Scale (adapted from the Children’s Cancer and Leukaemia Group); Usage of GI concomitant medication;Timepoint(s) of evaluation of this end point: PK: Day 8 of each treatment period; Safety: from screening until 30 days after last dose | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Safety and tolerability will be evaluated in terms of AEs, clinical safety laboratory assessments (clinical chemistry, haematology, urinalysis), physical examination, weight, vital signs, ECG, ECHO or cardiac MRI, ophthalmologic assessment and performance status; Assessments related to AEs will include: occurrence/frequency, relationship to study intervention, CTCAE grade, seriousness, death, AEs leading to discontinuation of study intervention, AEs of special interest 2. Plasma concentrations and PK parameters of selumetinib and N-desmethyl selumetinib after multiple dose administration, including, but not limited to: Cmax, AUClast, tmax, tlast;Timepoint(s) of evaluation of this end point: PK: Day 8 of each treatment period; Safety: from screening until 30 days after last dose | — |
Countries
Poland, Russian Federation, Spain, United States
Contacts
Public ContactInformation centre
AstraZeneca
Outcome results
None listed