KOMET: Efficacy and Safety of Selumetinib in Adults With NF1 Who Have Symptomatic, Inoperable Plexiform Neurofibromas
Study Details
Study Description
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 |
---|---|---|
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Phase 3 |
Detailed Description
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Arm A Selumetinib |
Drug: Selumetinib
Selumetinib oral capsules (10 mg and 25 mg)
Other Names:
|
Placebo Comparator: Arm B Placebo |
Other: Placebo
Placebo oral capsules for Selumetinib masking (10 mg and 25 mg)
|
Outcome Measures
Primary Outcome Measures
- Confirmed Objective Response Rate (ORR) for Arm A versus Arm B [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 [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 [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 [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 [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 [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 [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 [Approximately 3 years]
Difference in change from baseline between Arm A and Arm B
- Health Related Quality of Life (HRQoL) outcomes assessed using PlexiQoL [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 [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 [Approximately 3 years]
Selumetinib and N-desmethyl selumetinib plasma concentrations assessment
Eligibility Criteria
Criteria
Key Inclusion Criteria:
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Adults ≥ 18 years at enrollment with diagnosis of NF1 with symptomatic, inoperable PN
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At least one inoperable target PN measurable by volumetric MRI analysis
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Chronic target PN pain score documented for minimum period during screening period
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Stable chronic PN pain medication use at enrollment
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Adequate organ and marrow function
Key Exclusion Criteria:
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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)
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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
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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
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Ophthalmological findings/conditions including intraocular pressure > 21 mmHg, RPED/CSR or RVO
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Prior exposure to MEK inhibitors
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Research Site | Gainesville | Florida | United States | 32610 |
2 | Research Site | Rockville | Maryland | United States | 20852 |
3 | Research Site | Saint Louis | Missouri | United States | 63156 |
4 | Research Site | Commack | New York | United States | 11725 |
5 | Research Site | Richmond | Virginia | United States | 23219 |
6 | Research Site | Melbourne | Australia | 3000 | |
7 | Research Site | St Leonards | Australia | 2065 | |
8 | Research Site | Porto Alegre | Brazil | 90035-903 | |
9 | Research Site | Ribeirão Preto | Brazil | 14051-140 | |
10 | Research Site | São Paulo | Brazil | 045202-001 | |
11 | Research Site | Calgary | Alberta | Canada | T2N 4N2 |
12 | Research Site | Toronto | Ontario | Canada | M5G 2C4 |
13 | Research Site | Montreal | Quebec | Canada | H4A 3J1 |
14 | Research Site | Beijing | China | 100070 | |
15 | Research Site | Beijing | China | 100730 | |
16 | Research Site | Guangzhou | China | 510060 | |
17 | Research Site | Shenyang | China | 110001 | |
18 | Research Site | Creteil | France | 94010 | |
19 | Research Site | Lyon | France | 69008 | |
20 | Research Site | Nantes cedex 1 | France | 44093 | |
21 | Research Site | Toulouse Cedex 09 | France | 31059 | |
22 | Research Site | Hamburg | Germany | 20246 | |
23 | Research Site | Hamburg | Germany | 20246 | |
24 | Research Site | Tübingen | Germany | 72076 | |
25 | Research Site | Würzburg | Germany | 97080 | |
26 | Research Site | Milano | Italy | 20133 | |
27 | Research Site | Napoli | Italy | 80131 | |
28 | Research Site | Roma | Italy | 00165 | |
29 | Research Site | Trieste | Italy | 34100 | |
30 | Research Site | Minato-ku | Japan | 105-8471 | |
31 | Research Site | Nagoya-shi | Japan | 466-8560 | |
32 | Research Site | Shinjuku-ku | Japan | 160-8582 | |
33 | Research Site | Bydgoszcz | Poland | 85-094 | |
34 | Research Site | Gdańsk | Poland | 80-952 | |
35 | Research Site | Moscow | Russian Federation | 115522 | |
36 | Research Site | Moscow | Russian Federation | 125047 | |
37 | Research Site | Moscow | Russian Federation | 125412 | |
38 | Research Site | Badalona | Spain | 08916 | |
39 | Research Site | Madrid | Spain | 28041 | |
40 | Research Site | London | United Kingdom | SE1 9RT | |
41 | 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)
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- D134BC00001
- 2020-005607-39