Everolimus and LongActing Octreotide Trial in Polycystic Livers

Brief Title

Everolimus and LongActing Octreotide Trial in Polycystic Livers

Official Title

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

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.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Liver volume

Secondary Outcome

 Symptoms

Condition

Polycystic Liver Disease

Intervention

Everolimus

Study Arms / Comparison Groups

 Everolimus + octreotide LAR
Description:  Octreotide LAR combined with everolimus

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

44

Start Date

June 2010

Completion Date

July 2012

Primary Completion Date

July 2012

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
      

Gender

All

Ages

18 Years - 70 Years

Accepts Healthy Volunteers

No

Contacts

Joost PH Drenth, MD, PhD, , 

Location Countries

Netherlands

Location Countries

Netherlands

Administrative Informations


NCT ID

NCT01157858

Organization ID

CSMS995 ANLIIT


Responsible Party

Principal Investigator

Study Sponsor

Radboud University

Collaborators

 Novartis

Study Sponsor

Joost PH Drenth, MD, PhD, Principal Investigator, Radboud University


Verification Date

June 2015