Paraneoplasia remote effect of cancer
Conditions
Interventions
Treatment will be initiated with an oral loading dose of 6 mg sirolimus per day
for three consecutive days followed by oral maintenance dosing of 3 mg/day. The
dosing will be adjusted weekly to main
Sponsors
Erasmus MC, Universitair Medisch Centrum Rotterdam
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
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
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 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint of the study is the functional and neurological improvement after 8 wees of sirolimus. Functional improvement is defined as a 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. | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary research variables are anti-Hu antibody titers in serum and CSF, antigen specific T cells in blood and CSF, oculomotor function, sirolimus concentration in serum and CSF and MDR1 polymorphisms and improvement in the Barthel Index, AMC Linear Disability Score and the PNS Neurological scale. | — |
Countries
Netherlands
Outcome results
None listed