Everolimus and LongActing Octreotide Trial in Polycystic Livers

Condition(s) targeted: Polycystic Liver Disease

Intervention: Everolimus (Drug); Octreotide LAR (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: Radboud University

Official(s) and/or principal investigator(s):
Joost PH Drenth, MD, PhD, Principal Investigator, Affiliation: Radboud University
Melissa Chrispijn, MD, Study Director, Affiliation: Radboud University

Overall contact:
Melissa Chrispijn, MD, Phone: +3124 3614760, Email: M.Chrispijn@mdl.umcn.nl

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.

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

Study design: Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Liver volume

Secondary outcome:

Symptoms

Quality of Life

Responders

Adverse events

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.

Minimum age: 18 Years. Maximum age: 70 Years. Gender(s): Both.

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

Melissa Chrispijn, MD, Phone: +3124 3614760, Email: M.Chrispijn@mdl.umcn.nl

Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, Nijmegen 6500 HB, Netherlands; Recruiting
Melissa Chrispijn, MD, Phone: +3124 3614760, Email: M.Chrispijn@mdl.umcn.nl
Joost PH Drenth, MD, PhD, Phone: +3124 3614760, Email: joostphdrenth@cs.com
Joost PH Drenth, MD, PhD, Principal Investigator
Melissa Chrispijn, MD, Sub-Investigator

Starting date: June 2010
Last updated: July 6, 2010