Phase II Trial of LBH589 (Panobinostat) in Adult Patients With Recurrent Malignant Gliomas
The prognosis for recurrent malignant gliomas remains dismal despite advances in
neurological surgery, radiation oncology and chemotherapy. Median overall survival remains
a mere 14.6 months and 2 yr survival 25% (Stupp et al.) Novel treatments are clearly needed
for recurrent gliomas.
Preclinical data suggests that histone deacetylase inhibition may be an effective treatment
for recurrent malignant gliomas.
In 1999, in the Proceedings of the National Academy of Sciences, Saito reported that
MS-27-275, a benzamide derivative and inhibitor of histone deacetylase, inhibited the growth
of several different human tumor cell lines.
The drug you are being asked to take is called LBH589 or panobinostat. It belongs to a new
class of drugs called "histone deacetylase inhibitors." Histones are proteins located in
the nucleus of cells that bind to DNA, the chemical that makes up genes. These proteins
help control which genes are turned "on" and "off". Studies have shown that drugs like
panobinostat (LBH589) may lead to tumor cell death.
Before starting on-study, we will require that some standard blood tests be done. You may
have other tests done as well.
LBH589 (panobinostat) is a drug that you will take three times weekly by mouth on Monday,
Wednesday and Friday. You will take the capsules with an 8 ounce glass of water (not
grapefruit or orange juice) on an empty stomach at least 2 hours after meals and 2 hours
before next meal. Cycles are twenty eight (28) days long.
The study drug may affect your heart rhythm. Therefore, we will closely monitor your heart
by doing an electrocardiogram (ECG) while you are taking the study drug. On the first day
that you start taking the drug, we will record your ECG at several different time points:
three ECG's at 5 minute intervals before you take your first dose and then again at 2 hours,
4-6 hours and 24-32 hours after you take your first dose. On days 5 and 19 of the first
cycle (the first twenty eight days) we will also obtain (3) more ECG's: one before you take
your daily dose and then two more at 2 hours and 4-6 hours after taking the medication.
On future cycles (cycle 2 and thereafter) we will obtain single ECG's on days # 5 and 22 if
there had been no prior abnormal readings.
You will return to clinic for follow-up examination midway through the first cycle and then
again upon completion of the first cycle and each following cycle.
Follow-up blood tests will be obtained at the end of the first, second and fourth weeks of
the first cycle and then at the end of each following cycle.
Follow-up MRI (or CAT) scans will be obtained according to standard of care after each
second cycle unless medically indicated at other time points.
Other scans, such as PET scans, may be obtained if medically indicated as per standard of
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label
To generate preliminary data of anti-tumor efficacy of LBH589 in adults with recurrent malignant gliomas.
J. Paul Duic, MD
Long Island Brain Tumor Center at Neurological Surgery PC / Long Island Neuro-Oncology Associates
United States: Food and Drug Administration
|Long Island Brain Tumor Center at Neurological Surgery PC / Long Island Neuro-Oncology Associates||Commack, New York 11725|