Everolimus and LongActing Octreotide Trial in Polycystic Livers (ELATE)

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

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.

Study Overview

• Status: Completed
• Conditions: Polycystic Liver Disease
• Intervention / Treatment: Drug: Everolimus; Drug: Octreotide LAR

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.

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • Nijmegen, Netherlands, 6500 HB
    • Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Everolimus + octreotide LAR; Octreotide LAR combined with everolimus	Drug: Everolimus; 2.5 mg every day orally; Other Names: Afinitor; Drug: Octreotide LAR; 40 mg every 28 days IM; Other Names: Sandostatine LAR
Active Comparator: Octreotide LAR; Octreotide LAR monotherapy	Drug: Octreotide LAR; 40 mg every 28 days IM; Other Names: Sandostatine LAR

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symptoms	Change in symptoms, measured by GI-questionnaire	baseline and 12 months
Quality of Life	Change in quality of life, measured by EuroQoL-questionnaire	baseline and 12 months
Responders	Proportion of patients having any reduction in total liver volume after 12 months	baseline and 12 months
Adverse events	Adverse events that occur in these 12 months	During 12 months of treatment

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Collaborators: Novartis
• Investigators: Principal Investigator: Joost PH Drenth, MD, PhD, Radboud University Medical Center; Study Director: Melissa Chrispijn, MD, Radboud University Medical Center

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: July 6, 2010
• First Submitted That Met QC Criteria: July 6, 2010
• First Posted (Estimate): July 7, 2010

Study Record Updates

• Last Update Posted (Estimate): June 29, 2015
• Last Update Submitted That Met QC Criteria: June 26, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: liver cyst
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Physiological Effects of Drugs; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gastrointestinal Agents; Antineoplastic Agents, Hormonal; Octreotide; Everolimus
• Other Study ID Numbers: CSMS995 ANLIIT