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Everolimus and LongActing Octreotide Trial in Polycystic Livers (ELATE)

Primary Purpose

Polycystic Liver Disease

Status
Completed
Phase
Phase 2
Locations
Netherlands
Study Type
Interventional
Intervention
Everolimus
Octreotide LAR
Sponsored by
Radboud University Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Polycystic Liver Disease focused on measuring liver cyst

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Everolimus + octreotide LAR

Octreotide LAR

Arm Description

Octreotide LAR combined with everolimus

Octreotide LAR monotherapy

Outcomes

Primary Outcome Measures

Liver volume
change of total liver volume in terms of percentage from baseline to 12 months as determined by CT

Secondary Outcome Measures

Symptoms
Change in symptoms, measured by GI-questionnaire
Quality of Life
Change in quality of life, measured by EuroQoL-questionnaire
Responders
Proportion of patients having any reduction in total liver volume after 12 months
Adverse events
Adverse events that occur in these 12 months

Full Information

First Posted
July 6, 2010
Last Updated
June 26, 2015
Sponsor
Radboud University Medical Center
Collaborators
Novartis
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1. Study Identification

Unique Protocol Identification Number
NCT01157858
Brief Title
Everolimus and LongActing Octreotide Trial in Polycystic Livers
Acronym
ELATE
Official Title
Everolimus Added to Long Acting Octreotide as a Volume Reducing Treatment of Polycystic Livers
Study Type
Interventional

2. Study Status

Record Verification Date
June 2015
Overall Recruitment Status
Completed
Study Start Date
June 2010 (undefined)
Primary Completion Date
July 2012 (Actual)
Study Completion Date
July 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Radboud University Medical Center
Collaborators
Novartis

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Polycystic Liver Disease
Keywords
liver cyst

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
44 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Everolimus + octreotide LAR
Arm Type
Active Comparator
Arm Description
Octreotide LAR combined with everolimus
Arm Title
Octreotide LAR
Arm Type
Active Comparator
Arm Description
Octreotide LAR monotherapy
Intervention Type
Drug
Intervention Name(s)
Everolimus
Other Intervention Name(s)
Afinitor
Intervention Description
2.5 mg every day orally
Intervention Type
Drug
Intervention Name(s)
Octreotide LAR
Other Intervention Name(s)
Sandostatine LAR
Intervention Description
40 mg every 28 days IM
Primary Outcome Measure Information:
Title
Liver volume
Description
change of total liver volume in terms of percentage from baseline to 12 months as determined by CT
Time Frame
at baseline and at 12 months
Secondary Outcome Measure Information:
Title
Symptoms
Description
Change in symptoms, measured by GI-questionnaire
Time Frame
baseline and 12 months
Title
Quality of Life
Description
Change in quality of life, measured by EuroQoL-questionnaire
Time Frame
baseline and 12 months
Title
Responders
Description
Proportion of patients having any reduction in total liver volume after 12 months
Time Frame
baseline and 12 months
Title
Adverse events
Description
Adverse events that occur in these 12 months
Time Frame
During 12 months of treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joost PH Drenth, MD, PhD
Organizational Affiliation
Radboud University Medical Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Melissa Chrispijn, MD
Organizational Affiliation
Radboud University Medical Center
Official's Role
Study Director
Facility Information:
Facility Name
Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre
City
Nijmegen
ZIP/Postal Code
6500 HB
Country
Netherlands

12. IPD Sharing Statement

Citations:
PubMed Identifier
22104015
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.
Results Reference
derived

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Everolimus and LongActing Octreotide Trial in Polycystic Livers

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