Everolimus and LongActing Octreotide Trial in Polycystic Livers

Polycystic Liver Disease Clinical Trial

— ELATE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01157858
• Other study ID #: CSMS995 ANLIIT
• Status: Completed
• Phase: Phase 2
• First received: July 6, 2010
• Last updated: June 26, 2015
• Start date: June 2010
• Est. completion date: July 2012

Study information

• Verified date: June 2015
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Medical Ethics Review Committee (METC)Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: July 2012
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Cysts
• Liver Diseases
• Polycystic Liver Disease

Intervention

Drug:
• Everolimus
2.5 mg every day orally
• Octreotide LAR
40 mg every 28 days IM

Locations

Country	Name	City	State
Netherlands	Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre	Nijmegen

Sponsors (2)

Lead Sponsor	Collaborator
Radboud University	Novartis

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Symptoms	Change in symptoms, measured by GI-questionnaire	baseline and 12 months	Yes
Secondary	Quality of Life	Change in quality of life, measured by EuroQoL-questionnaire	baseline and 12 months	No
Secondary	Responders	Proportion of patients having any reduction in total liver volume after 12 months	baseline and 12 months	No
Secondary	Adverse events	Adverse events that occur in these 12 months	During 12 months of treatment	Yes