Sirolimus (Rapamune®) for the treatment of anti-Hu associated paraneoplastic neurological syndromes - Sirolimus for Hu-PNS

• Conditions: Paraneoplastic Neurological Syndromes associated with anti-Hu antibodies; MedDRA version: 9.1Level: LLTClassification code 10014619Term: Encephalomyelitis

• Registration Number: EUCTR2008-000793-20-NL
• Lead Sponsor: Erasmus MC

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-03-06
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

i)PEM/PSN associated with high (>=1:400 by IIF) titer anti-Hu antibodies.
ii)IIF (indirect immunofluorescence) has been confirmed by Western blotting using purified HuD fusion protein as substrate.
iii)The neurological symptoms must still be progressing defined as neurological deterioration over the last 4 weeks.
iv)Patients aged >=18 years.
v)Patients who receive or will receive concomitant anti-tumor therapy are allowed to participate.
vi)Patients who have given written informed consent.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

i)Patients who have reached a neurological plateau phase more than 4 weeks before inclusion date (‘damage is done’).
ii)Patients who are unwilling to undergo lumbar puncture.
iii)Liver enzyme elevations of more than 5-fold normal values
iv)Renal failure (GFR < 30 ml/min)
v)Extreme hypertriglyceridemia (> 10 mmol/L) and extreme hypercholesterolemia (> 10 mmol/L)
vi)Active infection
vii)Women of childbearing potential who are pregnant or lactating, seeking pregnancy or failing to take adequate contraceptive precautions.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The main objective of the trial is to study the efficacy of sirolimus in paraneoplastic neurological syndromes associated with anti-Hu antibodies.<br>;Secondary Objective: Secondary objectives are to correlate clinical improvement with anti-Hu antibody titers in serum and cerebrospinal fluid (CSF), HuD specific T cells in blood and CSF, sirolimus levels in blood and CSF and with MDR1 polymorphism.;Primary end point(s): The primary endpoint of the study is the functional and neurological improvement after 8 weeks of sirolimus. Functional improvement is defined as an decrease of one point or more on the Rankin scale after the 8th week of sirolimus as compared to the baseline evaluation. Improvement of neurological impairment is defined as a positive score (>0) in the EFIT overall evaluation after the 8th week of sirolimus as compared to the baseline evaluation.