Everolimus and LongActing Octreotide Trial in Polycystic Livers (ELATE)

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