Everolimus and LongActing Octreotide Trial in Polycystic Livers

• Status: Completed
• Trial end date: 2012-07-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Radboud University
• Collaborator: Novartis
• Treatments: Everolimus; Octreotide; Sirolimus

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