Everolimus and LongActing Octreotide Trial in Polycystic Livers

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
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.

Official Title
-----------------
Everolimus Added to Long Acting Octreotide as a Volume Reducing Treatment of Polycystic Livers

Conditions
-----------------
Polycystic Liver Disease

Intervention / Treatment
-----------------
* Drug: Everolimus
* Drug: Octreotide LAR


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 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 Dyspnea Early satiety Back pain Nausea/vomiting Anorexia Weight loss Jaundice Informed consent, patients are willing and able to comply with the study drug regimen and all other study requirements Exclusion Criteria: 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Everolimus + octreotide LAR<br>Octreotide LAR combined with everolimus | Drug: Everolimus<br>* 2.5 mg every day orally<br>* Other names: Afinitor;Drug: Octreotide LAR<br>* 40 mg every 28 days IM<br>* Other names: Sandostatine LAR;|
| Active Comparator: Octreotide LAR<br>Octreotide LAR monotherapy | Drug: Octreotide LAR<br>* 40 mg every 28 days IM<br>* Other names: Sandostatine LAR;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Liver volume | change of total liver volume in terms of percentage from baseline to 12 months as determined by CT | at baseline and at 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Symptoms | Change in symptoms, measured by GI-questionnaire | baseline and 12 months | 
| Quality of Life | Change in quality of life, measured by EuroQoL-questionnaire | baseline and 12 months | 
| Responders | Proportion of patients having any reduction in total liver volume after 12 months | baseline and 12 months | 
| Adverse events | Adverse events that occur in these 12 months | During 12 months of treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
liver cyst