Everolimus Added to Long Acting Octreotide as a Volume Reducing Treatment of Polycystic Livers
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- Liver volume
研究概览
简要总结
The aim of this study is to reduce polycystic liver volume by treating with octreotide, whether or not combined with everolimus; to assess whether combination therapy of everolimus and octreotide gives a bigger reduction of polycystic liver volume than octreotide monotherapy.
详细描述
This is a single center randomized, open-label, parallel study comparing the safety and efficacy of everolimus-octreotide LAR treatment to monotherapy octreotide LAR in adult symptomatic patients with polycystic livers because of polycystic liver disease (PCLD).
We aim to include 44 patients affected by a polycystic liver either due to PCLD, 22 patients in the combination group and 22 patients in the mono therapy group.The duration of the trial will be 52 weeks. The treatment will be 48 weeks and the last control visit will take place four weeks after the treatment.
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
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18 < age ≤ 70 years
- •Polycystic liver disease (PCLD), defined as ≥ 20 liver cysts
- •Total liver volume must be at least 2500 mL
- •Symptomatic defined as ECOG-PS ≥ 1 (see fig 3.1)38, and having at least three out of ten PCLD symptoms:
- •Abdominal pain
- •Abdominal distension
- •Abdominal fullness
- •Early satiety
- •Back pain
- •Nausea/vomiting
- •Weight loss
- •Informed consent, patients are willing and able to comply with the study drug regimen and all other study requirements
排除标准
- •ADPKD patients
- •Use of oral anticonceptives or estrogen supplementation
- •Females who are pregnant or breast-feeding or patients of reproductive potential not employing an effective method of birth control. Women of childbearing potential must have a negative serum pregnancy test within 48 hours prior to the administration of study medication.
- •Intervention (aspiration or surgical intervention) within three months before baseline
- •Treatment with somatostatin analogues within three months before baseline
- •Patients with a kidney transplant
- •History or other evidence of chronic pulmonary disease associated with functional limitation
- •History of severe cardiac disease (eg, NYHA Functional Class III or IV, myocardial infarction within 6 months, ventricular tachyarrhythmias requiring ongoing treatment, unstable angina or other significant cardiovascular diseases). In addition, patients with documented or presumed coronary artery disease or cerebrovascular disease should not be enrolled.
- •History or other evidence of severe illness or any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study
- •Symptomatic gallstones (octreotide decreases gall bladder volume)
- •Hypercholesterolemia (fasting cholesterol > 8 mmol/l) or hypertriglyceridaemia (> 5 mmol/l) not controlled by lipid lowering therapy
- •Granulocytopenia (white blood cell < 3,000/mm3) or thrombocytopenia (platelets < 100,000/mm3)
- •Infection with hepatitis B, hepatitis C, HIV, TBC (in medical history)
- •Mental illness that interferes with the patient ability to comply with the protocol
- •Drug or alcohol abuse within one year of baseline
- •Co-medication with strong inhibitor of CYP3A4 and or P-gp like voriconazole, ketoconazole, diltiazem, verapamil, erythromycin or with a strong CYP3A4 and or P-gp inductor like rifampicin
- •Known hypersensitivity to everolimus or one of its excipients
- •Enrolment in another clinical trial of an investigational agent while participating in this study
- •Moderate or severe reaction on contrast in medical history
- •Treatment with I131 during the course of the trial
- •Use of metformin
- •Morbus Kahler or Morbus Waldenstrom with excretion of light chains in urine in medical history
- •Kidney dysfunction (MDRD-GFR < 60 ml/min/1.73m2 and ECC < 60 ml/min, calculated by the Cockcroft-Gault formula); in case of decreased body muscle mass, exact ECC is measured using serum and urine creatinine
研究组 & 干预措施
Everolimus + octreotide LAR
Octreotide LAR combined with everolimus
干预措施: Everolimus (Drug)
Everolimus + octreotide LAR
Octreotide LAR combined with everolimus
干预措施: Octreotide LAR (Drug)
Octreotide LAR
Octreotide LAR monotherapy
干预措施: Octreotide LAR (Drug)
结局指标
主要结局
Liver volume
时间窗: at baseline and at 12 months
change of total liver volume in terms of percentage from baseline to 12 months as determined by CT
次要结局
- Responders(baseline and 12 months)
- Symptoms(baseline and 12 months)
- Quality of Life(baseline and 12 months)
- Adverse events(During 12 months of treatment)
研究者
Joost Drenth
MD, PhD
Radboud University Medical Center