A Two-staged, Phase 2/3, Randomized, Multicenter Study to Evaluate the Efficacy and Safety of REC-2282 in Participants With Progressive NF2 Mutated Meningiomas
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 25
- 试验地点
- 20
- 主要终点
- Cohort A: Number of Participants with Progression-free survival (PFS) at 6 Months
研究概览
简要总结
This is a two-staged, Phase 2/3, randomized, multi-center study to investigate the efficacy and safety of REC-2282 in participants with progressive NF2 mutated meningiomas.
详细描述
Cohort A (Phase 2) will provide early data on efficacy and safety of REC-2282 in participants with progressive NF2 mutated meningiomas, and provide guidance for the dose in the confirmatory part of the study (Cohort B, Phase 3). The purpose of Cohort B of the study is to assess the efficacy and safety of REC-2282 compared with placebo in participants with progressive NF2 mutated meningiomas.
In both cohorts, there will be a screening period of up to 8 weeks, a treatment period, a 4-week safety follow-up period after the end of treatment, and a 6-month post-study follow-up. The first 8 participants enrolled in Cohort A will complete a food effect run-in sub study. At the end of the study period, participants may be offered participation in an open-label extension (OLE) period.
In Cohort A, adult participants will be randomized to one of two dose levels of REC-2282.
In Cohort B, participants will be randomized to REC-2282 treatment (dose to be determined from Cohort A) arm or placebo arm in a ratio of 2:1.
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
- Double (Participant, Investigator)
盲法说明
Masking applies to Cohort B only.
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥12 years of age and weighing at least 40 kg
- •Progressive meningioma that is amenable to volumetric analysis
- •Has either 1) sporadic meningioma with confirmed NF2 mutation; or, 2) confirmed diagnosis of NF2 disease (revised Manchester criteria); or, 3) at least one NF2-related tumor (with pathogenic germline or proven mosaic NF2 variant)
- •Adequate bone marrow function
- •Has provided written informed consent/assent to participate in the study
排除标准
- •Progressive disease associated with significant or disabling clinical symptoms likely to require surgery or radiation therapy within the next 3 months.
- •Received prior surgery, radiosurgery, or laser interstitial thermal therapy in the target tumor, or immediately adjacent to the target tumor within 12 months prior to screening.
- •Received an anti- tumor agent for meningioma within 3 months, or 5 half-lives (whichever is longer), prior to screening.
- •History of an active malignancy within the previous 3 years except for localized cancers that are considered cured, and, in the opinion of the investigator, present a low risk of recurrence.
- •Received another investigational drug within 30 days prior to screening
- •Pregnant, lactating, or is planning to attempt to become pregnant or impregnate someone during this study or within 90 days after the last dosing cycle.
研究组 & 干预措施
Cohort B REC-2282
Participants will receive REC-2282.
干预措施: REC-2282 (Drug)
Cohort A Adults, REC-2282 60 mg
Adult participants will receive REC-2282.
干预措施: REC-2282 (Drug)
Cohort A Adolescents, REC-2282
Adolescent participants will receive REC-2282.
干预措施: REC-2282 (Drug)
Cohort B Placebo
Participants will receive placebo.
干预措施: Placebo (Drug)
Cohort A Adults, REC-2282 40 mg
Adult participants will receive REC-2282.
干预措施: REC-2282 (Drug)
结局指标
主要结局
Cohort A: Number of Participants with Progression-free survival (PFS) at 6 Months
时间窗: 6 months
In Cohort A, PFS is defined as the number of participants who are alive and progression-free at 6 months with progression defined as having an increase of 20% or more in the target tumor identified.
Cohort B: Number of Participants with PFS up to 3 years
时间窗: Up to 3 years
In Cohort B, PFS is defined as the time from the date of randomization until disease progression or death from any cause, whichever occurs first.
次要结局
- Cohort A: Number of Participants with PFS at 12 and 24 Months(12 and 24 Months)
- Cohort A: Change from Baseline in Target Tumor Volume at 6 Months(6 months)
- Cohorts A and B: Objective Response Rate (ORR)(Up to 3 years)
- Cohorts A and B: Disease Control Rate (DCR)(Up to 3 years)
- Cohorts A and B: Time to Response (TTR)(Up to 3 years)
- Cohorts A and B: Duration of Response (DOR)(Up to 3 years)
- Cohorts A and B: Time to Surgery/radiation for Target Tumors(Up to 3 years)
- Cohorts A and B: Maximum Observed Plasma Concentration (Cmax) of REC-2282(Up to 3 years)
- Cohorts A and B: Time to Maximum Plasma Concentration (Tmax) of REC-2282(Up to 3 years)
- Cohorts A and B: Area under the curve from 0 to 24hr (AUC) of REC-2282(Predose to 24 hours postdose)