Non-randomised Open Label Pilot Study of Sirolimus Therapy for Segmental Overgrowth Due to PIK3CA- Related Overgrowth
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 22
- 主要终点
- Measure of the relative percentage of the excess tissue volume evolution at the affected site by volumetric MRI.
研究概览
简要总结
It was found that people who have an excessive growth in one or more parts of their body and normal growth in other parts, may have a change in genes responsible for controlling cell growth. This genetic discovery identified a possible treatment for this overgrowth, called Sirolimus.
This is a pilot study, which help the investigators prepare a larger international study, which will aim to determine whether a treatment based Sirolimus is able to stop the excessive growth of one or more parties of their body in people who carry a genetic change in the PIK3CA gene (phosphatidylinosilol-3-kinase encoded by the gene PIK3CA).
详细描述
The duration of participation is 15 months:
- Visit screening: blood test, pre-clinical evaluation, urine collection and chest X-ray.
- First 6 months: participants will have their overgrowth monitored. This step includes 2 visits taking place at the University Hospital of Dijon: complete clinical evaluation, MRI of the body part by the overgrowth and Dual-energy X-ray absorptiometry (DXA).
- Next 6 months: participants will take Sirolimus. This step includes 2 visits (4 and 13 weeks after the start of treatment at local hospital): blood test, urine collection and clinical evaluation.
and 1 end of study visit after 6 months of treatment taking place at the University Hospital of Dijon: blood test, complete clinical evaluation, urine collection, MRI and DXA.
Participants will have several blood and urine tests between visits (1 and 2 weeks after the start of treatment at a local laboratory).
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
- 3 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Post-zygotic PIK3CA mutation
- •Age: 3-65 years
- •Measurable overgrowth, in current progression or with clinical history of overgrowth progression
- •Patient clinically stable
- •Presence of a disability, social or cosmetic impairment requiring treatment from the patient perspective,
- •Written informed consent form signed and dated by the subject or by the patient's legal representative
排除标准
- •Pregnancy or lactation
- •Women and men of reproductive age without any effective method of contraception (during treatment and up to 12 weeks after sirolimus discontinuation)
- •Hypersensitivity to the active substance (sirolimus) or to any of the excipients
- •Impossibility to obtain written informed consent form signed by the subject or the patient's legal representative, or vulnerable adults
- •Treatment with Sirolimus in the last 4 weeks before the trial
- •Personal history of malignancy or current investigations for suspected malignancy
- •Active skin infection requiring antibiotics or antiviral treatments
- •HIV or hepatitis B or C infection
- •Past history of Mycobacterium tuberculosis infection
- •Active pneumopathy
- •Uncontrolled infection
- •Chronic liver disease (ASAT or Alanine amino transférase (ALAT)> 3 times upper normal limit)
- •Stage 3 (or more) chronic renal insufficiency (eGFR< 60mls/min)
- •Neutropenia with neutrophiles < 1.0 x10^9/L
- •Uncontrolled dyslipidemia
- •Inability to attend study visits
结局指标
主要结局
Measure of the relative percentage of the excess tissue volume evolution at the affected site by volumetric MRI.
时间窗: Change from baseline at 6 and 12 months
次要结局
- quality of life measured by a questionnaire in the pre- and post-treatment periods(At 6 and 12 months)
- Measure sites of overgrowth by DXA, MRI and circumferential measurements(Change from baseline at 6 and 12 months)
- To determine optimal sirolimus dosing algorithms by plasma assay(12 months)
- Number of hospitalisation and surgery(12 months)