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