Clinical trial • Phase III • Neurology|Rare Disease
SELUMETINIB (selumetinib hyd-sulfate) for Neurofibromatosis type 1 (NF1) with symptomatic, inoperable plexiform neurofibromas
Phase III trial of SELUMETINIB (selumetinib hyd-sulfate) for Neurofibromatosis type 1 (NF1) with symptomatic, inoperable plexiform neurofibromas.
Overview
- Trial Therapeutic Area
- Neurology|Rare Disease
- Trial Disease
- Neurofibromatosis type 1 (NF1) with symptomatic, inoperable plexiform neurofibromas
- Trial Stage
- Phase III
- Drug Modality
- Small molecule
- Orphan Drug
- Yes
Key dates
- Initial CTIS Submission Date
- 11-04-2024
- First CTIS Authorization Date
- 21-05-2024
Trial design
Randomised, selumetinib orally bid (experimental arm); placebo to match selumetinib capsules, 10 and 25 mg, orally bid (placebo comparator arm).-controlled Phase III trial in Germany, Italy, Spain and others.
- Randomised
- Yes
- Comparator
- Selumetinib orally bid (experimental arm); Placebo to match Selumetinib capsules, 10 and 25 mg, orally bid (placebo comparator arm).
- Target Sample Size
- 96
Eligibility
Recruits 96 No vulnerable populations selected (isVulnerablePopulationSelected=false). Participants are adults (≥18 years) and informed consent is from the adult participant; no pediatric assent procedures indicated..
- Vulnerable Population
- No vulnerable populations selected (isVulnerablePopulationSelected=false). Participants are adults (≥18 years) and informed consent is from the adult participant; no pediatric assent procedures indicated.
Inclusion criteria
- {"criterion_text":"- Adults ≥ 18 years at enrollment with diagnosis of NF1 with symptomatic, inoperable PN\n- At least one target PN measurable by volumetric MRI analysis\n- Chronic target PN pain score documented for minimum period during screening period\n- Stable chronic PN pain medication use at enrollment\n- Adequate organ and marrow function"}
Exclusion criteria
- {"criterion_text":"- Confirmed or suspected malignant glioma or MPNST (low grade glioma, including optic glioma not requiring systemic therapy or radiation therapy are exempt from this exclusion)\n- 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\n- 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\n- Ophthalmological findings/conditions including intraocular pressure > 21 mmHg, RPED/CSR or RVO\n- Prior exposure to MEK inhibitors"}
Endpoints
Primary endpoints
- {"endpoint_text":"- Objective Response Rate (ORR) using volumetric MRI analysis as determined by ICR per REiNS criteria.","definition_or_measurement_approach":"ORR assessed using volumetric MRI analysis as determined by Independent Central Review (ICR) per REiNS criteria."}
Secondary endpoints
- {"endpoint_text":"- Change from baseline in chronic target PN pain intensity.\n- Change from baseline in PlexiQoL total score.\n- Objective Response Rate.\n- Duration of Response.\n- Progression Free Survival.\n- Time to progression.\n- Time to Response.\n- Best percentage change from baseline in target PN vol.\n- Pain palliation, pain medication use, pain interference, physical functioning, health related quality of life PROs&health status.\n- Safety&tolerability.\n- Plasma concentrations&PK parameters of selumetinib&Ndesmethyl selumetinib.","definition_or_measurement_approach":"Endpoints are generally measured as change from baseline (for pain intensity and PlexiQoL), standard oncology metrics (ORR, Duration of Response, PFS, Time to progression, Time to Response), volumetric MRI for target PN volume changes, patient-reported outcomes for pain palliation/physical functioning/HRQoL, safety and tolerability by standard safety assessments, and plasma concentrations/PK parameters measured for selumetinib and N-desmethyl selumetinib."}
Recruitment
- Planned Sample Size
- 96
- Recruitment Window Months
- 58
- Consent Approach
- Informed consent obtained from adult participants (participants are ≥18 years). Subject Information Sheets and Informed Consent Forms (L1 SIS and ICF) are available for adult participants and for pregnant partners; ICF documents are provided in multiple languages across member states (including German, Italian, Polish, Spanish, French and English as indicated by available SIS/ICF documents). No pediatric assent arrangements are indicated.
Geography
- Total Number Of Sites
- 10
- Total Number Of Participants
- 49
Germany
- Earliest CTIS Part Ii Submission Date
- 21-03-2024
- Latest Decision Or Authorization Date
- 16-10-2025
- Processing Time Days
- 574
- Number Of Sites
- 3
- Number Of Participants
- 10
Sites
- Site Name
- Universitaetsklinikum Wuerzburg AöR
- Department Name
- Neurochirurgische Klinik und Poliklinik des Universitätsklinikums
- Principal Investigator Name
- Cordula Matthies
- Principal Investigator Email
- Matthies_C@ukw.de
- Contact Person Name
- Cordula Matthies
- Contact Person Email
- Matthies_C@ukw.de
- Site Name
- University Medical Center Hamburg-Eppendorf
- Department Name
- Klinik und Poliklinik f. Neurologie
- Principal Investigator Name
- Said Farschtschi
- Principal Investigator Email
- s.farschtschi@uke.de
- Contact Person Name
- Said Farschtschi
- Contact Person Email
- s.farschtschi@uke.de
- Site Name
- Universitaetsklinikum Tuebingen AöR
- Department Name
- Klinik für Neurochirurgie Pädiatrische Neurochirurgie und periphere Neurochirurgie
- Principal Investigator Name
- Martin Schuhmann
- Principal Investigator Email
- Martin.Schuhmann@med.uni-tuebingen.de
- Contact Person Name
- Martin Schuhmann
- Contact Person Email
- Martin.Schuhmann@med.uni-tuebingen.de
Italy
- Earliest CTIS Part Ii Submission Date
- 21-03-2024
- Latest Decision Or Authorization Date
- 20-10-2025
- Processing Time Days
- 578
- Number Of Sites
- 2
- Number Of Participants
- 9
Sites
- Site Name
- Azienda Ospedaliera Universitaria Universita' Degli Studi Della Campania Luigi Vanvitelli
- Department Name
- Dipartimento della donna, del bambino e di chirurgia generale e specialistica
- Principal Investigator Name
- Silverio Perrotta
- Principal Investigator Email
- Silverio.PERROTTA@unicampania.it
- Contact Person Name
- Silverio Perrotta
- Contact Person Email
- Silverio.PERROTTA@unicampania.it
- Site Name
- IRCCS Foundation Istituto Neurologico Carlo Besta
- Department Name
- Neurological science
- Principal Investigator Name
- Marica Eoli
- Principal Investigator Email
- Marica.Eoli@istituto-besta.it
- Contact Person Name
- Marica Eoli
- Contact Person Email
- Marica.Eoli@istituto-besta.it
Spain
- Earliest CTIS Part Ii Submission Date
- 21-03-2024
- Latest Decision Or Authorization Date
- 23-10-2025
- Processing Time Days
- 581
- Number Of Sites
- 2
- Number Of Participants
- 8
Sites
- Site Name
- Hospital Germans Trias I Pujol
- Department Name
- Servicio de Oncologia
- Principal Investigator Name
- Ignacio Blanco Guillermo
- Principal Investigator Email
- iblanco.germanstrias@gencat.cat
- Contact Person Name
- Ignacio Blanco Guillermo
- Contact Person Email
- iblanco.germanstrias@gencat.cat
- Site Name
- Hospital Universitario 12 De Octubre
- Department Name
- Servicio de Oncologia
- Principal Investigator Name
- Juan Manuel Sepulveda Sanchez
- Principal Investigator Email
- sepulvedasanchez@seom.org
- Contact Person Name
- Juan Manuel Sepulveda Sanchez
- Contact Person Email
- sepulvedasanchez@seom.org
France
- Earliest CTIS Part Ii Submission Date
- 21-03-2024
- Latest Decision Or Authorization Date
- 17-10-2025
- Processing Time Days
- 575
- Number Of Sites
- 2
- Number Of Participants
- 12
Sites
- Site Name
- Hôpital Henri Mondor
- Department Name
- Service de Dermatologie
- Principal Investigator Name
- Laura Fertitta
- Principal Investigator Email
- laura.fertitta@aphp.fr
- Contact Person Name
- Laura Fertitta
- Contact Person Email
- laura.fertitta@aphp.fr
- Site Name
- Centre Hospitalier Universitaire De Toulouse
- Department Name
- Service de Dermatologie
- Principal Investigator Name
- Maëlla Severino-Freire
- Principal Investigator Email
- severino-freire.m@chu-toulouse.fr
- Contact Person Name
- Maëlla Severino-Freire
- Contact Person Email
- severino-freire.m@chu-toulouse.fr
Poland
- Earliest CTIS Part Ii Submission Date
- 21-03-2024
- Latest Decision Or Authorization Date
- 21-10-2025
- Processing Time Days
- 579
- Number Of Sites
- 1
- Number Of Participants
- 10
Sites
- Site Name
- Szpital Uniwersytecki Nr 1 Im. Dr. A. Jurasza W Bydgoszczy
- Department Name
- Klinika Pediatrii, Hematologii i Onkologii
- Principal Investigator Name
- Jan Styczynski
- Principal Investigator Email
- jstyczynski@cm.umk.pl
- Contact Person Name
- Jan Styczynski
- Contact Person Email
- jstyczynski@cm.umk.pl
Sponsor
Primary sponsor
- Full Name
- Astrazeneca AB
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- Sweden
Contract research organisations
- Name
- Parexel International (IRL) Limited
- Responsibilities
- sponsorDuties codes: 1,12,14,5,8; contact Clinicaltrial.Enquiries@parexel.com; phone +35314739500
Third parties
- {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"sponsorDuties codes: 1,12,14,5,8","organisation_type":"Pharmaceutical company"}
Investigational products
- Investigational Product Name
- SELUMETINIB
- Active Substance
- SELUMETINIB (selumetinib hyd-sulfate)
- Modality
- Small molecule
- Routes Of Administration
- ORAL USE
- Route
- oral
- Orphan Designation
- Yes
- Frequency
- bid
- Investigational Product Name
- Placebo to match Selumetinib capsules, 10 and 25 mg.
- Modality
- Other
- Routes Of Administration
- ORAL (matched capsules)
- Route
- oral
- Frequency
- bid
Related trials
Other published trials that may interest you.
- NIPOCALIMAB for Chronic inflammatory demyelinating polyneuropathy
- ROZANOLIXIZUMAB for Myelin oligodendrocyte glycoprotein antibody-associated disease (MOG-AD)
- Propranolol for Von Hippel-Lindau disease
- BEXICASERIN HYDROCHLORIDE for Developmental and Epileptic Encephalopathies
- DESCARTES-08 for Generalized myasthenia gravis|Myasthenia gravis|AChR myasthenia gravis