An Open-Label, Single-Arm Exploratory Clinical Study of Everolimus for the Treatment of Vascular Malformations
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Objective Response Rate (ORR) assessed by MRI
研究概览
简要总结
This study is a single-arm exploratory trial conducted by Xuanwu Hospital, Capital Medical University, aiming to evaluate the efficacy and safety of everolimus monotherapy in adult patients with vascular malformations.
详细描述
This study is a single-arm exploratory trial designed to evaluate the efficacy and safety of everolimus monotherapy in adult patients with vascular malformations.
A total of 10 participants aged 18 to 65 years with a confirmed diagnosis of vascular malformation will be enrolled. Eligible patients must be deemed by the investigator to be unsuitable for effective surgical treatment. After screening, qualified participants will receive oral everolimus once daily in continuous cycles of 28 days. The daily dosage of everolimus for adult patients will be 10 mg. Treatment will continue until disease progression, intolerable toxicity, lack of clinical benefit as determined by the investigator, study termination, or any other pre-defined discontinuation criteria-whichever occurs first.
The primary objective of this study is to assess the therapeutic efficacy of everolimus in patients with vascular malformations, primarily through evaluation of lesion volume using MRI sequences. All participants will undergo MRI-based target lesion volume analysis and assessments of microbleeding, iron deposition, and hemorrhage risk during the screening period, at the end of treatment cycles 3, 6, and 12, every 6 cycles thereafter, and at the end-of-treatment (EOT) visit. Clinical signs, symptom scores, and quality-of-life improvements will also be evaluated. The acceptable window for these assessments is ±7 days. If a participant has not undergone efficacy evaluation within 3 months, a final assessment should be conducted at the EOT visit.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Diagnosed with Hereditary Hemorrhagic Telangiectasia (HHT), Arteriovenous Malformation (AVM), or PTEN Hamartoma Tumor Syndrome (PHTS);
- •Patients who have previously received any of the following treatments after birth: participation in other interventional clinical trials targeting cerebral cavernous malformations (CM);
- •Presence of malignant tumors currently or within the past three years, except for curatively treated non-melanoma skin basal cell carcinoma, ductal carcinoma in situ of the breast, or cervical carcinoma in situ;
- •Unable to undergo MRI scans and/or have contraindications for MRI (e.g., interference from prosthetics, orthodontic devices, etc., affecting target lesion volume analysis on MRI);
- •Modified Rankin Scale (mRS) score of 5, respiratory failure, or currently experiencing severe bleeding requiring life-support treatment;
- •Severe renal failure (e.g., creatinine clearance \[CrCl] < 30 mL/min, or significantly elevated serum creatinine not correctable by other means), recent history (within past 3 months) of renal failure or end-stage renal disease without effective treatment, or currently undergoing dialysis;
- •Severe hepatic failure, including but not limited to: Child-Pugh Class C or higher, recent (within 3 months) uncontrolled symptoms related to hepatic failure such as ascites, jaundice, coagulopathy, or hepatic encephalopathy, or patients requiring liver transplantation;
- •Currently using other immunosuppressants or patients with immunodeficiency;
- •Patients requiring use of medications that interfere with or inhibit CYP3A4 enzyme activity, or medications such as cisapride or metoclopramide;
- •Patients with dysphagia, active gastrointestinal disorders, malabsorption syndrome, or other conditions that may affect the absorption of the investigational drug;
- •Interstitial pneumonitis, including clinically significant radiation pneumonitis;
- •Severe asthma;
- •Uncontrolled diabetes mellitus;
- •Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements;
- •First-degree relatives with a history of sudden cardiac death before the age of
- •First-degree relatives are defined as those with a direct bloodline, such as parents and children, grandparents and grandchildren, or maternal grandparents and maternal grandchildren;
- •Active bacterial, fungal, or viral infections, including active hepatitis B (HBsAg positive with HBV DNA > 1000 IU/mL or meeting local diagnostic criteria for active HBV infection), hepatitis C (HCV RNA positive), or HIV infection (HIV positive);
- •Pregnant or breastfeeding women. Any patient who becomes pregnant during the trial must withdraw from the study;
- •Known hypersensitivity to everolimus, other rapamycin derivatives, or any of the excipients in this product. Observed allergic reactions to everolimus or related compounds include but are not limited to: hypersensitivity, dyspnea, flushing, chest pain, or angioedema (e.g., airway or tongue swelling with or without respiratory compromise);
- •Other factors, as determined by the investigator, that may lead to early study termination, such as presence of other severe diseases (including psychiatric disorders) requiring concomitant treatment, significantly abnormal lab values, or social/family issues that may affect patient safety or data collection.
研究组 & 干预措施
An Open-Label, Single-Arm Exploratory Study of Everolimus
Subjects will receive everolimus 10 mg orally once daily in continuous 28-day treatment cycles, until the occurrence of disease progression, intolerable toxicity, lack of clinical benefit as determined by the investigator, end of study, or other protocol-specified criteria for treatment discontinuation (whichever occurs first).
干预措施: Everolimus 10mg daily (Drug)
结局指标
主要结局
Objective Response Rate (ORR) assessed by MRI
时间窗: 1 year
次要结局
- Duration of Response (DOR) and 1-year DOR rate assessed by MRI(1 year)
- Mean Percentage Reduction in Target Lesion Volume at 3, 6, and 12 Months Assessed by MRI(1 year)
- Changes in Perilesional Microbleeds and Iron Deposition at 3, 6, and 12 Months Assessed by MRI QSM Sequence.(1 year)
- Changes in lesion hemorrhage risk during the follow-up period(1 year)
- Changes in patients' clinical signs and symptom scores from baseline.(1 year)
- The frequency and severity of intracranial hemorrhage events during the follow-up period were assessed through clinical records, imaging examinations (MRI), and the mRS scoring system.(1 year)
- Disease Control Rate (DCR) assessed by MRI(1 year)
- Progression-Free Survival (PFS) and 1-year PFS rate assessed by MRI(1 year)
- The frequency and types of seizures during the follow-up period were recorded and assessed through seizure event logs and classification of seizure types.(1 year)