Clinical trial NCT01157858: Everolimus and LongActing Octreotide Trial in Polycystic Livers
Official title: Everolimus Added to Long Acting Octreotide as a Volume Reducing Treatment of Polycystic Livers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Polycystic Liver Disease
Keywords: liver cyst
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: Novartis
First posted: 2010-07-07
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Liver volume
timeFrame: at baseline and at 12 months
Secondary outcomes:
measure: Symptoms
timeFrame: baseline and 12 months
measure: Quality of Life
timeFrame: baseline and 12 months
measure: Responders
timeFrame: baseline and 12 months
measure: Adverse events
timeFrame: During 12 months of treatment
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre
Study officials:
affiliation: Radboud University Medical Center
name: Joost PH Drenth, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Radboud University Medical Center
name: Melissa Chrispijn, MD
role: STUDY_DIRECTOR
References:
citation: Chrispijn M, Drenth JP. Everolimus and long acting octreotide as a volume reducing treatment of polycystic livers (ELATE): study protocol for a randomized controlled trial. Trials. 2011 Nov 21;12:246. doi: 10.1186/1745-6215-12-246.