Efficacy and Safety of Selumetinib in Adults With NF1 Who Have Symptomatic, Inoperable Plexiform Neurofibromas (KOMET)
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT04924608 |
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Recruitment Status :
Active, not recruiting
First Posted : June 14, 2021
Last Update Posted : May 22, 2023
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Sponsor:
AstraZeneca
Collaborator:
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
AstraZeneca
- Study Details
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Brief Summary:
A global study to demonstrate the effectiveness of selumetinib in participants with NF1 who have symptomatic, inoperable plexiform neurofibromas.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Neurofibromatosis 1 Plexiform Neurofibroma (PN) | Drug: Selumetinib Other: Placebo | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 146 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase III, Multicentre, International Study With a Parallel, Randomised, Double-blind, Placebo-controlled, 2 Arm Design to Assess the Efficacy and Safety of Selumetinib in Adult Participants With NF1 Who Have Symptomatic, Inoperable Plexiform Neurofibromas (KOMET) |
| Actual Study Start Date : | November 19, 2021 |
| Estimated Primary Completion Date : | October 24, 2024 |
| Estimated Study Completion Date : | May 22, 2025 |
Resource links provided by the National Library of Medicine
MedlinePlus related topics:
Neurofibromatosis
Drug Information available for:
Selumetinib
| Arm | Intervention/treatment |
|---|---|
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Experimental: Arm A
Selumetinib
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Drug: Selumetinib
Selumetinib oral capsules (10 mg and 25 mg)
Other Name: AZD6244 |
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Placebo Comparator: Arm B
Placebo
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Other: Placebo
Placebo oral capsules for Selumetinib masking (10 mg and 25 mg) |
Primary Outcome Measures :
- Confirmed Objective Response Rate (ORR) for Arm A versus Arm B [ Time Frame: Approximately 3 years ]ORR will be defined as the proportion of patients who have a confirmed complete response or confirmed partial response as determined by ICR per REiNS criteria
Secondary Outcome Measures :
- Change in chronic target PN pain intensity from baseline for Arm A versus Arm B as assessed using a PRO questionnaire [ Time Frame: Approximately 3 years ]Difference in mean change from baseline in chronic target PN pain intensity score between Arm A and Arm B, obtained using an NRS-11 scale to assess pain intensity of a target plexiform neurofibroma
- Duration of response (DoR) for Arm A [ Time Frame: Approximately 3 years ]DoR will be defined as the time from the date of first documented response (which is subsequently confirmed) until progression by ICR per REiNS criteria or death due to any cause
- Progression Free Survival (PFS) for Arm A [ Time Frame: Approximately 3 years ]PFS will be defined as the time from first selumetinib dose until date of disease progression by ICR per REiNS criteria or death due to any cause
- Time to progression (TTP) for Arm A [ Time Frame: Approximately 3 years ]TTP is defined as the time from the date of first selumetinib dose until date of disease progression by ICR per REiNS criteria
- Time to Response (TTR) for Arm A [ Time Frame: Approximately 3 years ]TTR is defined as the time from date of first selumetinib dose until the date of objective response by ICR per REiNS criteria
- Target PN volume for Arm A vs Arm B [ Time Frame: Approximately 3 years ]Difference in best percentage change from baseline in target PN volume by ICR per REiNS criteria
- Physical functioning assessed using PROMIS physical function items [ Time Frame: Approximately 3 years ]Difference in change from baseline between Arm A and Arm B
- Health Related Quality of Life (HRQoL) outcomes assessed using PlexiQoL [ Time Frame: Approximately 3 years ]Difference in change from baseline between Arm A and Arm B
Other Outcome Measures:
- Safety and tolerability of selumetinib as assessed by number and grade of adverse events [ Time Frame: Approximately 3 years ]Adverse events are defined according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0
- Pharmacokinetics (PK) of selumetinib for exposure-response analyses [ Time Frame: Approximately 3 years ]Selumetinib and N-desmethyl selumetinib plasma concentrations assessment
Information from the National Library of Medicine
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Key Inclusion Criteria:
- Adults ≥ 18 years at enrollment with diagnosis of NF1 with symptomatic, inoperable PN
- At least one inoperable 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
Key Exclusion Criteria:
- 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)
- 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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04924608
Locations
| United States, Florida | |
| Research Site | |
| Gainesville, Florida, United States, 32610 | |
| United States, Maryland | |
| Research Site | |
| Rockville, Maryland, United States, 20852 | |
| United States, Missouri | |
| Research Site | |
| Saint Louis, Missouri, United States, 63156 | |
| United States, New York | |
| Research Site | |
| Commack, New York, United States, 11725 | |
| Australia | |
| Research Site | |
| Melbourne, Australia, 3000 | |
| Research Site | |
| St Leonards, Australia, 2065 | |
| Brazil | |
| Research Site | |
| Porto Alegre, Brazil, 90035-903 | |
| Research Site | |
| Ribeirão Preto, Brazil, 14051-140 | |
| Research Site | |
| São Paulo, Brazil, 045202-001 | |
| Canada, Ontario | |
| Research Site | |
| Toronto, Ontario, Canada, M5G 2C4 | |
| Canada, Quebec | |
| Research Site | |
| Montreal, Quebec, Canada, H4A 3J1 | |
| China | |
| Research Site | |
| Beijing, China, 100070 | |
| Research Site | |
| Beijing, China, 100730 | |
| Research Site | |
| Guangzhou, China, 510060 | |
| Research Site | |
| Shenyang, China, 110001 | |
| France | |
| Research Site | |
| Creteil, France, 94010 | |
| Research Site | |
| Lyon, France, 69008 | |
| Research Site | |
| Toulouse Cedex 09, France, 31059 | |
| Germany | |
| Research Site | |
| Hamburg, Germany, 20246 | |
| Research Site | |
| Tübingen, Germany, 72076 | |
| Research Site | |
| Würzburg, Germany, 97080 | |
| Italy | |
| Research Site | |
| Milano, Italy, 20133 | |
| Research Site | |
| Napoli, Italy, 80131 | |
| Research Site | |
| Roma, Italy, 00165 | |
| Japan | |
| Research Site | |
| Minato-ku, Japan, 105-8471 | |
| Research Site | |
| Nagoya-shi, Japan, 466-8560 | |
| Research Site | |
| Shinjuku-ku, Japan, 160-8582 | |
| Poland | |
| Research Site | |
| Bydgoszcz, Poland, 85-094 | |
| Research Site | |
| Gdańsk, Poland, 80-952 | |
| Russian Federation | |
| Research Site | |
| Moscow, Russian Federation, 115522 | |
| Research Site | |
| Moscow, Russian Federation, 125412 | |
| Spain | |
| Research Site | |
| Badalona, Spain, 08916 | |
| Research Site | |
| Madrid, Spain, 28041 | |
| United Kingdom | |
| Research Site | |
| London, United Kingdom, SE1 9RT | |
| Research Site | |
| Manchester, United Kingdom, M20 4BX | |
Sponsors and Collaborators
AstraZeneca
Merck Sharp & Dohme LLC
Investigators
| Principal Investigator: | Geraldine O'Sullivan Coyne, MD PhD | National Cancer Institute (NCI) |
| Responsible Party: | AstraZeneca |
| ClinicalTrials.gov Identifier: | NCT04924608 |
| Other Study ID Numbers: |
D134BC00001 2020-005607-39 ( EudraCT Number ) |
| First Posted: | June 14, 2021 Key Record Dates |
| Last Update Posted: | May 22, 2023 |
| Last Verified: | May 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | 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 Materials: |
Study Protocol Statistical Analysis Plan (SAP) |
| 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. |
| URL: | https://astrazenecagroup-dt.pharmacm.com/DT/Home |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by AstraZeneca:
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Neurofibromatosis Type 1 NF1 Plexiform Neurofibroma (PN) |
PNs Selumetinib MEK inhibitor |
Additional relevant MeSH terms:
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Neurofibromatoses Neurofibromatosis 1 Neurofibroma Neurofibroma, Plexiform Nerve Sheath Neoplasms Neoplasms, Nerve Tissue Neoplasms by Histologic Type Neoplasms Neoplastic Syndromes, Hereditary |
Neurocutaneous Syndromes Nervous System Diseases Heredodegenerative Disorders, Nervous System Neurodegenerative Diseases Genetic Diseases, Inborn Peripheral Nervous System Diseases Neuromuscular Diseases Peripheral Nervous System Neoplasms Nervous System Neoplasms |