NCT04924608进行中（未招募）3 期
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)
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- AstraZeneca
- 入组人数
- 145
- 试验地点
- 35
- 主要终点
- 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.
研究概览
简要总结
A global study to demonstrate the effectiveness of selumetinib in participants with NF1 who have symptomatic, inoperable plexiform neurofibromas.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Arm A
Experimental
Selumetinib
干预措施: Selumetinib (Drug)
Arm B
Placebo Comparator
Placebo
干预措施: Placebo (Other)
结局指标
主要结局
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.
时间窗: 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)
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.
次要结局
- (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(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(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(Baseline and end of Cycle 12 of study intervention)
研究者
研究点 (35)
Loading locations...
相似试验
招募中
2 期
Selumetinib for the Prevention of Plexiform Neurofibroma Growth in NF Type 1Neurofibromatosis 1Plexiform NeurofibromaNCT06188741University of Alabama at Birmingham200
终止
2 期
Study of Sutent®/Sunitinib (SU11248) in Subjects With NF-1 Plexiform NeurofibromasPlexiform NeurofibromasNeurofibromatosisNF1NCT01402817Indiana University19
进行中（未招募）
2 期
MEK 1/2 Inhibitor Selumetinib (AZD6244 Hydrogen Sulfate) in Adults With Neurofibromatosis Type 1 (NF1) and Inoperable Plexiform NeurofibromasNeurofibromatosis 1 (NF1)Plexiform Neurofibromas (PN)NCT02407405National Cancer Institute (NCI)36
已完成
1 期
Study of Selumetinib in Patients With Previously Treated or Untreated Advanced/Metastatic NSCLCNon Small Cell Lung CancerNCT01783197Canadian Cancer Trials Group39
已完成
1 期
Assess Safety & Efficacy of Selumetinib When Given in Combination With Standard First Line Treatment for Advanced Non-small Cell Lung CancerLocally Advanced or Metastatic NSCL Cancer Stage IIIB IVNCT01809210AstraZeneca55
相关资讯
Health Canada Approves Koselugo for Adult Neurofibromatosis Type 1 Patients with Plexiform Neurofibromas- Health Canada has approved Koselugo (selumetinib) for adult patients with neurofibromatosis type 1 who have symptomatic, inoperable plexiform neurofibromas, addressing a significant unmet medical need.
- The approval was based on the KOMET Phase III trial, which demonstrated a statistically significant 20% objective response rate compared to 5% with placebo.
- This marks the first treatment option for Canadian adults with this rare genetic condition, as Koselugo was previously only available for pediatric patients.
- The drug has been recently listed on the common drug list under Canada's National Strategy for Drugs for Rare Disease, reflecting its clinical impact.6 months agoSelumetinib Demonstrates Efficacy in Adult NF1 Patients with Inoperable Plexiform Neurofibromas- Selumetinib significantly improved the objective response rate (ORR) compared to placebo in adult patients with neurofibromatosis type 1 (NF1) and symptomatic, inoperable plexiform neurofibromas (PN).
- The phase 3 KOMET trial met its primary endpoint, showing clinically meaningful benefits for adult NF1 patients, who currently have limited therapeutic options.
- The safety profile of selumetinib in the KOMET trial was consistent with previous findings in pediatric and adolescent patients, with no new safety signals identified.
- These results suggest that selumetinib could expand beyond pediatric use to treat adult patients with this rare genetic condition, addressing a critical unmet need.last yearKoselugo Shows Promise in Phase 3 Trial for Adult Neurofibromatosis Type 1- KOSELUGO (selumetinib) demonstrated a statistically significant and clinically meaningful improvement in objective response rate (ORR) versus placebo in adults with neurofibromatosis type 1 (NF1).
- The Phase 3 KOMET trial is the largest global, randomized, double-blind, placebo-controlled study in adults with NF1 and symptomatic, inoperable plexiform neurofibromas (PN).
- The safety profile of KOSELUGO in the adult trial was consistent with previous trials in children, with no new safety signals identified, suggesting potential for expanded use.
- Alexion and Merck plan to share the KOMET trial data with regulatory authorities, potentially paving the way for the first approved targeted therapy for adults with NF1 plexiform neurofibromas.last year