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

Phase 2

Completed

• Conditions: Paraneoplasia; remote effect of cancer; 10003816; 10007951

• Registration Number: NL-OMON32182
• Lead Sponsor: Erasmus MC, Universitair Medisch Centrum Rotterdam

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 13 May 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 17

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.

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
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary endpoint of the study is the functional and neurological<br /><br>improvement after 8 wees of sirolimus. Functional improvement is defined as a<br /><br>decrease of one point or more on the Rankin scale after the 8th week of<br /><br>sirolimus as compared to the baseline evaluation. Improvement of neurological<br /><br>impairment is defined as a positive score (>0) in the EFIT overall evaluation<br /><br>after the 8th week of sirolimus as compared to the baseline evaluation.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>The secondary research variables are anti-Hu antibody titers in serum and CSF,<br /><br>antigen specific T cells in blood and CSF, oculomotor function, sirolimus<br /><br>concentration in serum and CSF and MDR1 polymorphisms and improvement in the<br /><br>Barthel Index, AMC Linear Disability Score and the PNS Neurological scale.</p><br>