A Randomized, Double-blind, Placebo-controlled Study of RAD0001 in the Treatment of Angiomyolipoma in Patients With Either Tuberous Sclerosis Complex (TSC) or Sporadic Lymphangioleiomyomatosis (LAM)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 118
- 试验地点
- 7
- 主要终点
- Angiomyolipoma Response Rate as Per Central Radiology Review
研究概览
简要总结
This study will evaluate the safety and efficacy of RAD001 in treating patients with Angiomyolipoma associated with Tuberous Sclerosis Complex or Sporadic Lymphangioleiomyomatosis.
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
- •Male or Female 18 years or older
- •Clinically definite diagnosis of Tuberous Sclerosis Complex according to the modified Gomez criteria or sporadic LAM (biopsy-proven or compatible chest CT scan)
- •Clinically definite diagnosis of renal angiomyolipoma
- •At least one Angiomyolipoma of ≥ 3 cm in its longest diameter using CT or MRI
- •Females of child bearing potential must use birth control and have documentation of negative pregnancy test
- •Written informed consent according to local guidelines
排除标准
- •Recent heart attack, cardiac related chest pain or stroke
- •Severely impaired lung function
- •Bleeding related to angiomyolipoma or embolization during 6 months prior to randomization
- •Clinically significant chylous ascites
- •Clinically significant hematological or hepatic abnormality
- •Severe liver dysfunction
- •Severe kidney dysfunction
- •Pregnancy or breast feeding
- •Current infection
- •History of organ transplant
- •Surgery within two months prior to study enrollment
- •Prior therapy with a medication in the same class as Everolimus
- •Recent use of an investigational drug
- •Bleeding diathesis or on oral anti-vitamin K medication
- •Uncontrolled high cholesterol
- •Uncontrolled diabetes
- •Inability to attend scheduled clinic visits
- •Patients with metal implants thus prohibiting MRI evaluations
- •Angiomyolipoma which requires surgery at the time of randomization
- •History of malignancy
- •Severe or uncontrolled medical conditions which would cause an unacceptable safety risk or compromise compliance with the protocol
研究组 & 干预措施
Everolimus
Study drug was given by continuous oral daily dosing of two 5 mg tablets.
干预措施: Everolimus (RAD001) (Drug)
Placebo
Placebo was given by continuous oral daily dosing of two 5 mg tablets.
干预措施: Everolimus Placebo (Drug)
结局指标
主要结局
Angiomyolipoma Response Rate as Per Central Radiology Review
时间窗: From date of randomization until the earliest date of first documented AML progression, date of further anti-AML medication (including open-label Everolimus)/surgery or up to 5.7 years
Angiomyolipoma response defined as the combination of the following criteria: reduction in angiomyolipoma volume of ≥ 50% relative to baseline, where angiomyolipoma volume was sum of volumes of all target lesions identified at baseline, and with a confirmatory scan performed approximately 12 weeks later (no sooner than 8 weeks later); no new angiomyolipoma lesions ≥ 1.0 cm in longest diameter were identified; there were no kidney increases in volume \> 20% from nadir. The patient did not have any angiomyolipoma-related bleeding of ≥ grade 2. For the everolimus (core/extension periods) treatment group, the baseline means the latest value on or before starting everolimus.
次要结局
- Skin Lesion Response Rate as Per Investigator (Only Patients With at Least One Skin Lesion at Baseline)(From date of randomization until the earliest date of first documented AML progression, date of further anti-AML medication (including open-label Everolimus)/surgery or up to 5.7 years)
- Change From Baseline in Plasma Angiogenic Molecules - Vascular Endothelial Growth Factor (VEGF) Marker(4 weeks, 12 weeks, 24 weeks, 36 weeks 48 weeks, 60 weeks, 72 weeks)
- Everolimus Trough Concentrations (Cmin)(Prior to dosing at weeks 2, 4, 12, 24, 48)
- Time to Angiomyolipoma Progression as Per Central Radiology Review(From date of randomization until the earliest date of first documented AML progression, date of further anti-AML medication (including open-label Everolimus)/surgery or up to about 5.7 years)
- Everolimus Blood Concentrations (C2h) at 2 Hours Post-dose(2 hours post-dose administration at Weeks 2, 4, 12, 24, 48)
- Percentage of Participants With Renal Impairment(Day 1 up to 28 days after end of treatment)
- Time to Angiomyolipoma Response - Only Everolimus Patients With Angiomyolipoma Response(From date of randomization until the earliest date of first documented AML progression, date of further anti-AML medication (including open-label Everolimus)/surgery or up to 5.7 years)
- Duration of Angiomyolipoma Response - Only Everolimus Patients With Angiomyolipoma Response(From date of randomization until the earliest date of first documented AML progression, date of further anti-AML medication (including open-label Everolimus)/surgery or up to about 5.7 years)
- Duration of Skin Lesion Response - Only Everolimus Patients With Best Overall Skin Lesion Response of Complete Clinical Response (CCR) or Partial Response (PR)(From date of randomization until the earliest date of first documented AML progression, date of further anti-AML medication (including open-label Everolimus)/surgery or up to about 5.7 years)