A Phase 2 interventional study of Selumetinib in Plexiform Neurofibromas (PN), sponsored by West China Hospital. Not yet recruiting at 1 site in China. Open to participants aged 3 Years to 18 Years. Per ClinicalTrials.gov, last updated 2025-01-08.
Sponsored by West China Hospital · Phase 2, Interventional, and Treatment
The goal of this study is to compare the efficacy and safety of low-dose and internationally recommended standard dose of selumetinib in the treatment of plexiform neurofibromas in Chinese children.
Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder that affects multiple organ systems, with an estimated prevalence of approximately 1/3000. Around 50% of NF1 develop plexiform neurofibromas (PN), which can exhibit invasive growth, leading to compression of surrounding tissues. PN can progress rapidly within a short period, resulting in severe deformities and functional impairments that significantly impact the patient's quality of life.
In 2020, selumetinib was approved in the United States for the treatment of symptomatic PN patients aged ≥2 years who were ineligible for surgery, bringing new breakthroughs to this large patient population in China. In recent years, clinical trials have been conducted in many countries and regions to evaluate the efficacy and safety of selumetinib in the treatment of PN. Studies have demonstrated that after one year of treatment, 70% of patients achieved confirmed partial lesion reduction, accompanied by significant improvements in pain symptoms and quality of life. Furthermore, the safety was favorable, with 97.7% of adverse reactions classified as Grade I or II. In China, a single-arm clinical trial involving 16 children also showed that all patients had controlled lesions, of which 63% of children had confirmed partial relief. However, the current dosage for children in China refers to the recommended value of Phase I clinical trials (25 mg/m²) in the United States. There remains a lack of pharmacokinetic and pharmacodynamic data specific to the Chinese population. Since racial differences can influence drug metabolism, the current dosage may exceed the tolerance level for some Chinese children, potentially increasing the risk of serious adverse reactions. Clinically, families frequently report a high incidence of adverse effects such as paronychia, abdominal pain, and rash.
Therefore, conducting a dose optimization study based on the Chinese population and exploring the efficacy and safety of low-dose selumetinib in the treatment of PN in Chinese children is of great significance. These efforts will guide clinical practice, reduce adverse reactions, and enhance treatment outcomes.
63 studies on the registry are indexed under Neurofibroma, Plexiform; 19 are open to participants now.
This study's planned enrollment of 50 is above the median of 36 across 43 interventional studies indexed under Neurofibroma, Plexiform.
Browse Neurofibroma, Plexiform studies →West China Hospital is the lead sponsor of 501 studies on the registry; 246 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The total daily dose is 25 mg/m², twice a day, once every 12 hours, and the treatment is continued and followed up for 24 cycles (28 days as one cycle).
Drug: Selumetinib
The total daily dose is 20 mg/m², twice a day, once every 12 hours, and the treatment is continued and followed up for 24 cycles (28 days as one cycle).
Drug: Selumetinib
Use of the internationally recommended standard dose and low dose of the same drug
Also known as: AZD6244, Koselugo
The change in tumor volume of plexiform neurofibromas
Treatment response was measured by volumetric magnetic resonance imaging (MRI) analysis performed at the start of treatment and after 3, 6, 9, 12, 18, and 24 cycles of treatment and independently assessed by 2 radiologists. Changes in PN size were categorized as further growth (increase of ≥20%), no change (\<20% increase and \<20% decrease), partial involution (decrease of ≥20% and \<75%), nearly complete involution (decrease of ≥75% and \<100%), or complete involution (100%).
Time frame: Once every 3 cycles for the first 12 cycles, once every 6 cycles for the next 12 cycles (each cycle is 28 days).
Frequency of adverse events
Frequency of adverse events (e.g. gastrointestinal disorders, eye disorders, skin disorders, paronychia, abnormal left ventricular ejection fraction, abnormal myocardial marker, abnormal liver function etc.) collected regularly during follow-up by the investigators and reported by the parents. All adverse events were collected and graded according to Common Terminology Criteria for Adverse Events, version 4.0 (CTCAE v4.0). The causality of the adverse event was determined by the multidisciplinary staff and was classified as definitively not related, probably not related, possibly related, probably related, or definitively related. Any dose reductions, interruptions, or cessations enacted at the discretion of the investigators were recorded.
Time frame: Once per cycle in the first 3 cycles, once every 3 cycles in the 4th to 12th cycles, and once every 6 cycles in the last 12 cycles (each cycle is 28 days).
Quality of life (QOL) in patients and their families
The Pediatric Quality of Life Inventory (PedsQLTM) 4.0 was used. This genetic core scale is a multidimensional child self-report and parent proxy report measure that assesses health-related quality of life (QOL) in children, adolescents, and young adults aged 2 to 25 years. The PedsQL contains 23 global core measures of QOL, including subscales assessing four domains (physical, emotional, social, and school functioning).
Time frame: Once every 3 cycles for the first 12 cycles, once every 6 cycles for the next 12 cycles (each cycle is 28 days).
The change of pain intensity
The Numerical Rating Scale-11 (NRS-11) was used. This scale is a self-report measure that assesses pain intensity on an 11-point numeric scale. It consists of a horizontal line with 0 on the right end, representing "no pain," and 10 on the left end, representing "the worst pain you can imagine." Children aged 8 to 18 years were asked to circle a number from 0 to 10 that best described their worst pain in the past week, including: 1) self-selected most important tumor pain, 2) physician-selected target tumor pain, 3) overall tumor pain, and 4) other types of pain.
Time frame: Once every 3 cycles for the first 12 cycles, once every 6 cycles for the next 12 cycles (each cycle is 28 days).
The change of pain interference
The Pain Interference Index (PII) is a six-item measure that assesses the extent to which pain has interfered with daily activities over the past week, including concentration, spending time with friends, leisure and physical activities, mood, and sleep. The scale was slightly adapted after translation into English, and a parallel parent version was developed and validated in parents of children with chronic pain. In this study, children aged 8 to 18 years completed the self-report PII, and parents of children aged 5 to 18 years completed the parent-report PII. The total PII score is the average of all six items.
Time frame: Once every 3 cycles for the first 12 cycles, once every 6 cycles for the next 12 cycles (each cycle is 28 days).
The change of physical functioning (mobility and upper extremity)
The Patient-Reported Outcome Measurement Information System (PROMIS®) Physical Function Mobility and Upper Extremity 8-item short forms were used. This short form is used to assess the ability of a person to perform a variety of physical functions over the past 7 days, ranging from motor movements (e.g., standing up from the floor) to activities including self-care skills and vigorous exercise. Children aged 8-18 years completed the Pediatric Self-Report Short Form, and parents of children aged 5-18 years completed the parallel Parent Report Form. These PROMIS Physical Functioning Short Forms demonstrated good psychometric properties, including good reliability and construct validity in adolescents with a variety of medical conditions.
Time frame: Once every 3 cycles for the first 12 cycles, once every 6 cycles for the next 12 cycles (each cycle is 28 days).
The change of neurocognitive abilities-attention and memory
The Continuous Performance Test (CPT) was used. It assesses the subject's attention, response control, and sustained attention ability by presenting continuous visual or auditory stimuli and requiring the subject to respond according to specific rules. The test content usually includes quickly identifying specific stimuli and responding while ignoring other distracting stimuli. Evaluation indicators include reaction time, accuracy of correct responses, frequency of impulsive responses, and the individual's ability to maintain attention during the task, helping to identify attention deficits or response control problems.
Time frame: Once every 3 cycles for the first 12 cycles, once every 6 cycles for the next 12 cycles(each cycle is 28 days).
The change of neurocognitive abilities-language ability
Peabody Picture Vocabulary Test (PPVT) was used. It is a standardized tool for assessing an individual's vocabulary comprehension ability. It presents a set of pictures and verbal words and asks the subject to choose the picture that best matches the meaning of the word. The test covers words of varying difficulty and assesses an individual's auditory comprehension of words. The main evaluation indicators include language comprehension level, vocabulary, and cognitive ability, which help detect language development, language disorders, and intelligence level.
Time frame: Once every 3 cycles for the first 12 cycles, once every 6 cycles for the next 12 cycles (each cycle is 28 days).
The change of neurocognitive abilities-executive function
The Stroop test was used. It assesses an individual's inhibitory control and selective attention. It consists of two tasks: one is to ask the subject to report the font color of a word while ignoring the meaning of the word (color word task), and the other is to simply report the font color (simple color task). The test evaluates an individual's cognitive inhibition ability in conflict situations by comparing the performance of these two tasks. The main evaluation indicators include reaction time, task accuracy, and conflict inhibition ability.
Time frame: Once every 3 cycles for the first 12 cycles, once every 6 cycles for the next 12 cycles (each cycle is 28 days).
Plan to share: No
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Studies of the drug tested here: AZD 6244