A Phase 3 interventional study of Selumetinib and Placebo in Neurofibromatosis 1 and Plexiform Neurofibroma (PN), sponsored by AstraZeneca. Active, not recruiting at 34 sites in 13 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-03-23.
Sponsored by AstraZeneca · Phase 3, Interventional, and Treatment
A global study to demonstrate the effectiveness of selumetinib in participants with NF1 who have symptomatic, inoperable plexiform neurofibromas.
This is a randomized, double-blind, placebo-controlled, 2 arm multicentre, global Phase III study to assess the efficacy and safety of selumetinib compared with placebo in adult participants with NF1 who have symptomatic, inoperable PN.
176 studies on the registry are indexed under Neurofibromatosis 1; 43 are open to participants now.
This study's enrollment of 145 is above the median of 35 across 114 interventional studies indexed under Neurofibromatosis 1.
Browse Neurofibromatosis 1 studies →AstraZeneca is the lead sponsor of 3,499 studies on the registry; 270 are open to participants now.
Of its 368 completed or terminated interventional studies of FDA-regulated products, 178 (48%) have results posted.
Counted across the registry records on this site, refreshed daily.
Key Inclusion Criteria:
Key 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.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
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.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
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.
Selumetinib
Drug: Selumetinib
Placebo
Other: Placebo
Selumetinib oral capsules (10 mg and 25 mg)
Also known as: AZD6244
Placebo oral capsules for Selumetinib masking (10 mg and 25 mg)
Confirmed Partial and Complete Response Rate (ORR) by End of Cycle 16 Using Volumetric MRI Analysis as Determined by ICR (Per REiNS Criteria) in Participants With NF1 Who Have Symptomatic, Inoperable PN.
Objective response rate is defined as the proportion of participants who have a confirmed CR (defined as disappearance of the target PN, confirmed by a consecutive scan within 3 to 6 months after the first response) or confirmed PR (defined as a target PN volume decrease ≥ 20%, compared to baseline, confirmed by a consecutive scan within 3 to 6 months after the first response) by end of Cycle 16 as determined by ICR per REiNS criteria. Increase in the volume of the target PN by 20% or more compared to baseline or the time of best response after documenting a PR is considered as PD.
Time frame: From first dose up until progression (if it occurs prior to the end of Cycle 16), or the last evaluable assessment up to and including the end of Cycle 16, excluding MRI during prolonged study intervention interruption (defined as interruption >= 28 days)
(First Key Secondary) The Difference of the Means in the Change From Baseline in PAINS-pNF Chronic Target PN Pain Intensity Score at Cycle 12 Between Selumetinib and Placebo, Primary Analysis
The PAINS-pNF (Pain Intensity Scale for Plexiform Neurofibroma) chronic target PN pain intensity measures the participants' experience of chronic PN-related pain intensity with score from 0 (no chronic tumor pain) to 10 (worst chronic tumor pain). Baseline PAINS-pNF chronic target PN pain score is defined as the average of the available daily PAINS-pNF chronic target PN pain scores in the screening perio, while for Cycle 12, it is defined as the average of the available daily scores for the 28-days cycle up to and including the last day assessment of cycle 12. The difference of the means in the change from baseline at Cycle 12 between selumetinib and placebo in participants with a PAINS-pNF chronic target PN pain score of ≥ 3 at baseline is presented.
Time frame: Baseline and end of cycle 12 of study intervention
(First Key Secondary) The Difference of the Means in the Change From Baseline in PAINS-pNF Chronic Target PN Pain Intensity Score at Cycle 12 Between Selumetinib and Placebo, Supplemental Analysis
The PAINS-pNF (Pain Intensity Scale for Plexiform Neurofibroma) chronic target PN pain intensity measures the participants' experience of chronic PN-related pain intensity with score from 0 (no chronic tumor pain) to 10 (worst chronic tumor pain). Baseline PAINS-pNF chronic target PN pain score is defined as the average of the available daily PAINS-pNF chronic target PN pain scores in the screening perio, while for Cycle 12, it is defined as the average of the available daily scores for the 28-days cycle up to and including the last day assessment of cycle 12. The difference of the means in the change from baseline at Cycle 12 between selumetinib and placebo participants is presented.
Time frame: Baseline and end of cycle 12 of study intervention
(Second Key Secondary Endpoint) The Difference of the Means in the Change From Baseline in PlexiQoL Total Score at Cycle 12
PlexiQoL (Plexiform Neurofibroma Quality of Life scale) is a patient-derived QoL measure specific to adults with NF1-associated PNs. It assesses the impact of PNs on patients' ability to fulfil their human needs. The measure consists of 18 dichotomous items with 0 =Not True and 1 = True. PlexiQoL total scores were calculated by the sum of all items to a maximum of 18, with lower scores indicating better quality of life. The change from baseline to the end of each cycle in PlexiQoL total score was derived as the PlexiQoL total score at the cycle 12 minus baseline PlexiQoL total score and presented.
Time frame: Baseline and end of Cycle 12 of study intervention
| Milestone | Selumetinib 25 mg/m2 | Placebo |
|---|---|---|
| Started | 71 | 74 |
| Completed | 0 | 0 |
| Not completed | 71 | 74 |
| Withdrew: Adverse event | 10 | 6 |
| Withdrew: Lost to follow-up | 1 | 1 |
| Withdrew: Ongoing at the data cut-off date | 54 | 60 |
| Withdrew: Progressive disease | 2 | 0 |
| Withdrew: Withdrawal by subject | 3 | 6 |
| Withdrew: Other reason | 1 | 1 |
Objective response rate is defined as the proportion of participants who have a confirmed CR (defined as disappearance of the target PN, confirmed by a consecutive scan within 3 to 6 months after the first response) or confirmed PR (defined as a target PN volume decrease ≥ 20%, compared to baseline, confirmed by a consecutive scan within 3 to 6 months after the first response) by end of Cycle 16 as determined by ICR per REiNS criteria. Increase in the volume of the target PN by 20% or more compared to baseline or the time of best response after documenting a PR is considered as PD.
| Percentage | Selumetinib 25 mg/m2 | Placebo |
|---|---|---|
| Confirmed Partial and Complete Response Rate (ORR) by End of Cycle 16 Using Volumetric MRI Analysis as Determined by ICR (Per REiNS Criteria) in Participants With NF1 Who Have Symptomatic, Inoperable PN. | 19.7 (11.2 to 30.9) | 5.4 (1.5 to 13.3) |
The PAINS-pNF (Pain Intensity Scale for Plexiform Neurofibroma) chronic target PN pain intensity measures the participants' experience of chronic PN-related pain intensity with score from 0 (no chronic tumor pain) to 10 (worst chronic tumor pain). Baseline PAINS-pNF chronic target PN pain score is defined as the average of the available daily PAINS-pNF chronic target PN pain scores in the screening perio, while for Cycle 12, it is defined as the average of the available daily scores for the 28-days cycle up to and including the last day assessment of cycle 12. The difference of the means in the change from baseline at Cycle 12 between selumetinib and placebo in participants with a PAINS-pNF chronic target PN pain score of ≥ 3 at baseline is presented.
| Scores on a scale | Selumetinib 25 mg/m2 | Placebo |
|---|---|---|
| (First Key Secondary) The Difference of the Means in the Change From Baseline in PAINS-pNF Chronic Target PN Pain Intensity Score at Cycle 12 Between Selumetinib and Placebo, Primary Analysis | -2.0 ± 0.30 | -1.3 ± 0.29 |
The PAINS-pNF (Pain Intensity Scale for Plexiform Neurofibroma) chronic target PN pain intensity measures the participants' experience of chronic PN-related pain intensity with score from 0 (no chronic tumor pain) to 10 (worst chronic tumor pain). Baseline PAINS-pNF chronic target PN pain score is defined as the average of the available daily PAINS-pNF chronic target PN pain scores in the screening perio, while for Cycle 12, it is defined as the average of the available daily scores for the 28-days cycle up to and including the last day assessment of cycle 12. The difference of the means in the change from baseline at Cycle 12 between selumetinib and placebo participants is presented.
| Scores on a scale | Selumetinib 25 mg/m2 | Placebo |
|---|---|---|
| (First Key Secondary) The Difference of the Means in the Change From Baseline in PAINS-pNF Chronic Target PN Pain Intensity Score at Cycle 12 Between Selumetinib and Placebo, Supplemental Analysis | -1.6 ± 0.22 | -0.9 ± 0.21 |
PlexiQoL (Plexiform Neurofibroma Quality of Life scale) is a patient-derived QoL measure specific to adults with NF1-associated PNs. It assesses the impact of PNs on patients' ability to fulfil their human needs. The measure consists of 18 dichotomous items with 0 =Not True and 1 = True. PlexiQoL total scores were calculated by the sum of all items to a maximum of 18, with lower scores indicating better quality of life. The change from baseline to the end of each cycle in PlexiQoL total score was derived as the PlexiQoL total score at the cycle 12 minus baseline PlexiQoL total score and presented.
| Scores on a scale | Selumetinib 25 mg/m2 | Placebo |
|---|---|---|
| (Second Key Secondary Endpoint) The Difference of the Means in the Change From Baseline in PlexiQoL Total Score at Cycle 12 | -0.4 ± 0.45 | -0.3 ± 0.44 |
Collected over All-cause mortality (death due to any cause) and Treatment emergent adverse events during randomised period, which is from the first dose of study intervention until the first date when selumetinib kit(s) are dispensed at Cycle 12 Day 28 (about 1 year), or 30 days after study intervention discontinuation, or up to one day prior to start of subsequent therapy, whichever occurs first. The medians of total treatment duration were 336 days for Selumetinib group and 335 days for Placebo group.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Selumetinib 25 mg/m2 | 0/71 (0%) | 10/71 (14.1%) | 70/71 (98.6%) |
| Placebo | 0/74 (0%) | 9/74 (12.2%) | 54/74 (73%) |
| Event | Selumetinib 25 mg/m2 | Placebo |
|---|---|---|
| NeurofibrosarcomaNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 1/71 | 3/74 |
| CellulitisInfections and infestations | 2/71 | 0/74 |
| PneumoniaInfections and infestations | 1/71 | 0/74 |
| Joint dislocationInjury, poisoning and procedural complications | 1/71 | 0/74 |
| Neurofibrosarcoma recurrentNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 1/71 | 0/74 |
| HeadacheNervous system disorders | 1/71 | 0/74 |
| ParaparesisNervous system disorders | 1/71 | 0/74 |
| Psychiatric decompensationPsychiatric disorders | 1/71 | 0/74 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 1/71 | 0/74 |
| Urinary tract infection bacterialInfections and infestations | 0/71 | 1/74 |
| Event | Selumetinib 25 mg/m2 | Placebo |
|---|---|---|
| Dermatitis acneiformSkin and subcutaneous tissue disorders | 42/71 | 8/74 |
| Blood creatine phosphokinase increasedInvestigations | 32/71 | 4/74 |
| DiarrhoeaGastrointestinal disorders | 30/71 | 9/74 |
| VomitingGastrointestinal disorders | 18/71 | 6/74 |
| NauseaGastrointestinal disorders | 18/71 | 12/74 |
| Covid-19Infections and infestations | 11/71 | 15/74 |
| FatigueGeneral disorders | 14/71 | 10/74 |
| Aspartate aminotransferase increasedInvestigations | 13/71 | 4/74 |
| AlopeciaSkin and subcutaneous tissue disorders | 13/71 | 8/74 |
| Dry skinSkin and subcutaneous tissue disorders | 13/71 | 4/74 |
| Age, Continuous(Years) | Selumetinib 25 mg/m2 | Placebo | Total |
|---|---|---|---|
| Mean | 32.6 ± 11.42 | 29.8 ± 8.72 | 31.2 ± 10.19 |
| Sex: Female, Male(Participants) | Selumetinib 25 mg/m2 | Placebo | Total |
|---|---|---|---|
| Female | 38 | 32 | 70 |
| Male | 33 | 42 | 75 |
| Ethnicity (NIH/OMB)(Participants) | Selumetinib 25 mg/m2 | Placebo | Total |
|---|---|---|---|
| Hispanic or Latino | 5 | 9 | 14 |
| Not Hispanic or Latino | 63 | 63 | 126 |
| Unknown or Not Reported | 3 | 2 | 5 |
| Baseline PAINS-pNF chronic target PN pain intensity score(Participants) | Selumetinib 25 mg/m2 | Placebo | Total |
|---|---|---|---|
| Baseline PAINS-pNF chronic target PN pain intensity score >= 3 | 50 | 53 | 103 |
| Baseline PAINS-pNF chronic target PN pain intensity score < 3 | 21 | 21 | 42 |
| Height(cm) | Selumetinib 25 mg/m2 | Placebo | Total |
|---|---|---|---|
| Mean | 163.517 ± 9.3702 | 165.798 ± 12.2517 | 164.698 ± 10.9784 |
| Weight(kg) | Selumetinib 25 mg/m2 | Placebo | Total |
|---|---|---|---|
| Mean | 65.896 ± 15.9763 | 66.271 ± 17.3971 | 66.087 ± 16.6596 |
| BSA(m^2) | Selumetinib 25 mg/m2 | Placebo | Total |
|---|---|---|---|
| Mean | 1.713 ± 0.2319 | 1.732 ± 0.2620 | 1.722 ± 0.2471 |
| Geographical region(count) | Selumetinib 25 mg/m2 | Placebo | Total |
|---|---|---|---|
| China | 11 | 13 | 24 |
| Europe (includes France, Germany, Italy, Poland, Russia, Spain, and United Kingdom) | 31 | 30 | 61 |
| Japan | 7 | 8 | 15 |
| Rest of World (includes Australia, Brazil, Canada, and United States) | 22 | 23 | 45 |
1 further baseline measures are reported on the registry.
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Supporting information: Study protocol, Statistical analysis plan
Time frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Data sharing details ↗ · astrazenecagroup-dt.pharmacm.com
This study is active, not recruiting, as verified in Mar 2026. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: AZD 6244