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Phase II Trial of LBH589 (Panobinostat) in Adult Patients With Recurrent Malignant Gliomas

Phase 2
18 Years
Not Enrolling
Recurrent Malignant Gliomas

Thank you

Trial Information

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

Inclusion Criteria:

- Recurrent malignant glioma with radiographic progression

- No more than three prior therapies.

- Male or female patients >=18 years old

- KPS >=60.

- Ability to provide written informed consent or consent obtained from responsible
healthcare proxy.

- Contrast-enhanced MRI within 2 weeks of enrollment.

- Life expectancy >= 8 weeks

- Neutrophils >1500/mm3

- Platelets > 100,000/mm3L

- Hemoglobin >=9 g/dL

- AST/SGOT and ALT/SGPT <= 2.5 x upper limit of normal (ULN) or < 5.0 x ULN if the
transaminase elevation is due to disease involvement

- Serum bilirubin <= 1.5 x ULN

- Serum creatinine <= 1.5 x ULN or 24-hour creatinine clearance >= 50 ml/min

- Total serum calcium or ionized calcium WNL

- Serum potassium WNL

- Serum sodium WNL

- Serum albumin >= LLN or 3g/dl

- Elevated Alkaline Phosphatase due to bone metastasis can be enrolled

- Baseline MUGA or ECHO must demonstrate LVEF >= the LLN

- TSH and free T4 WNL (patients may be on thyroid hormone replacement)

- Women of childbearing potential (WOCBP) must have a negative serum pregnancy test
within 7 days of the first administration of study treatment and must be willing to
use two methods of contraception one of them being a barrier method during the study
and for 3 months after last study drug administration.

- No concurrent antitumor therapy.

- No enzyme-inducing antiepileptic drugs.

- No significant comorbidities

- Patients must have recovered from toxic effects of prior therapy.

Exclusion criteria

- Prior HDAC, DAC, HSP90 inhibitors or valproic acid for the treatment of cancer

- Valproic acid for any medical condition during the study or within 5 days prior to
first LBH589 treatment

- Impaired cardiac function including:

- Screening ECG with a QTc > 450 msec

- Congenital long QT syndrome

- History of sustained ventricular tachycardia

- History of ventricular fibrillation or torsades de pointes

- Bradycardia < 50 beats per minute. Patients with a pacemaker and heart rate > = 50
beats per minute are eligible.

- Myocardial infarction or unstable angina within 6 months

- Congestive heart failure (NYHA class III or IV)

- RBBB and LAH (bifascicular block)

- Uncontrolled hypertension

- Concomitant use of drugs with a risk of causing torsades de pointes Concomitant use
of CYP3A4 inhibitors

- Patients with unresolved diarrhea

- Impairment of gastrointestinal (GI) function or GI disease that may significantly
alter absorption of LBH589

- Concurrent severe and/or uncontrolled medical conditions

- Chemotherapy, any investigational drug or major surgery < 4 weeks prior to starting
study drug or have not recovered from side effects of such therapy.

- Concomitant use of any anti-cancer therapy or radiation therapy.

- Women who are pregnant or breast feeding or women of childbearing potential (WOCBP)
not willing to use a double barrier method of contraception during the study and 3
months after the end of treatment. One of these methods of contraception must be a
barrier method.

- Male patients whose sexual partners are WOCBP not using a double method of
contraception during the study and 3 months after the end of treatment. One of these
methods must be a condom

- History of another primary malignancy within 5 years other than curatively treated
CIS of the cervix, or basal or squamous cell carcinoma of the skin

- Known human immunodeficiency virus (HIV) or hepatitis C positivity

- Significant history of non-compliance to medical regimens or inability to grant a
reliable informed consent

- More than three prior therapies

- Hepatic or renal diseases or any diseases that will obscure toxicity or alter drug

- Known active malignancies

- Active infection requiring iv antibiotics

- Systemic anticoagulants

- Enzyme-inducing antiepileptic drugs

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label

Outcome Measure:

To generate preliminary data of anti-tumor efficacy of LBH589 in adults with recurrent malignant gliomas.

Outcome Time Frame:

12 months

Safety Issue:


Principal Investigator

J. Paul Duic, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Long Island Brain Tumor Center at Neurological Surgery PC / Long Island Neuro-Oncology Associates


United States: Food and Drug Administration

Study ID:




Start Date:

November 2008

Completion Date:

April 2009

Related Keywords:

  • Recurrent Malignant Gliomas
  • LBH859
  • Panobinostat
  • GBM
  • Glioma
  • Glioblastoma
  • Astrocytoma
  • oligodendroglioma
  • oligoastrocytoma
  • gliosarcoma
  • anaplastic
  • Brain Neoplasms
  • Glioma



Long Island Brain Tumor Center at Neurological Surgery PC / Long Island Neuro-Oncology AssociatesCommack, New York  11725