Recurrent Malignant GliomasPhase 2NCT00848523
Study of LBH589 (Panobinostat) to Treat Malignant Brain Tumors
A Phase 2 study testing Panobinostat in people with Recurrent Malignant Gliomas, run by Neurological Surgery, P.C. at 2 sites in United States.
Trial summary
The drug LBH589 (panobinostat) is an experimental (investigational) drug that is being tested for recurrent (returning) malignant gliomas. An investigational drug is one that has not been approved by the U.S. Food and Drug Administration (FDA). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent Malignant Gliomas
- What is being tested?
- Panobinostat
- How many people
- 6 participants
- Where
- 2 sitesUnited States
- Study dates
- Nov 2008to Apr 2009
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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
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- 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 metabolism
- Known active malignancies
- Active infection requiring iv antibiotics
- Systemic anticoagulants
- Enzyme-inducing antiepileptic drugs
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Long Island Brain Tumor Center at Neurological Surgery PC / Long Island Neuro-Oncology Associates
Commack, New York, 11725
Long Island Brain Tumor Center at Neurological Surgery PC / Long Island Neuro-Oncology Associates
Great Neck, New York, 11021
About this study
Official title: Phase II Trial of LBH589 (Panobinostat) in Adult Patients With Recurrent Malignant Gliomas
The drug LBH589 (panobinostat) is an experimental (investigational) drug that is being tested for recurrent (returning) malignant gliomas. An investigational drug is one that has not been approved by the U.S. Food and Drug Administration (FDA). 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.
Read the detailed description
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 care.
- Conditions
- Recurrent Malignant Gliomas
- Being tested
- Panobinostat
- Keywords
- LBH859, Panobinostat, GBM, Glioma, Glioblastoma, Astrocytoma, oligodendroglioma, oligoastrocytoma, gliosarcoma, anaplastic
- Medical subject headings
- Glioma, Glioblastoma, Astrocytoma, Oligodendroglioma, Gliosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PanobinostatDrug
Also called LBH589
30 mg, three times a week, patients will continue with treatment until they experience unacceptable toxicity that precludes further treatment, disease progression, and/or at the discretion of the investigator.
What is being measured
The primary outcome is the main question the study is designed to answer.
To generate preliminary data of anti-tumor efficacy of LBH589 in adults with recurrent malignant gliomas.
Measured: 12 months
Secondary outcomes (2)
To determine primary efficacy endpoint PFS-6
Measured: 6 months
To determine objective response (CR + PR) Rate
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2009 (estimated)
- Study startNov 2008
- Primary completionApr 2009 (estimated)
- Study completionApr 2009
Why it stopped: insufficient accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent Malignant GliomasStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Neurological Surgery, P.C.
- Sponsor type
- University, hospital or other
- Investigators
- J. Paul Duic, MD, Principal investigator, Long Island Brain Tumor Center at Neurological Surgery PC / Long Island Neuro-Oncology AssociatesJai Grewal, MD, Principal investigator, Long Island Brain Tumor Center at Neurological Surgery PC/ Long Island Neuro-oncology Associates
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00848523
- Sponsor's protocol ID
- LIBTC-2008-1
- Status last verified
- Sep 2009
- First submitted
- 19 Feb 2009
- Last updated
- 16 Jul 2010
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 Jul 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of LBH589 (Panobinostat) in Adult Patients With Recurrent Malignant Gliomas
- ClinicalTrials.gov ID
- NCT00848523
- Acronym / sponsor ID
- LIBTC-2008-1
- Conditions
- Recurrent Malignant Gliomas
- Keywords
- LBH859, Panobinostat, GBM, Glioma, Glioblastoma, Astrocytoma, oligodendroglioma, oligoastrocytoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: insufficient accrual
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Neurological Surgery, P.C.University, hospital or other
- Study start
- Nov 2008
- Primary completion
- Apr 2009 (estimated)
- Study completion
- Apr 2009 (actual)
- First posted
- 20 Feb 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The drug LBH589 (panobinostat) is an experimental (investigational) drug that is being tested for recurrent (returning) malignant gliomas. An investigational drug is one that has not been approved by the U.S. Food and Drug Administration (FDA). 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.
Detailed description
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 care.
Study design
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- 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.
Key exclusion criteria (29 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PanobinostatAlso: LBH58930 mg, three times a week, patients will continue with treatment until they experience unacceptable toxicity that precludes further treatment, disease progression, and/or at the discretion of the investigator. | Drug | – |
Primary outcome
To generate preliminary data of anti-tumor efficacy of LBH589 in adults with recurrent malignant gliomas.
Time frame: 12 months
2 secondary outcomes
To determine primary efficacy endpoint PFS-6
Time frame: 6 months
To determine objective response (CR + PR) Rate
Time frame: 12 months
Results and safety
The study was stopped early (reason given: insufficient accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jul 2010.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
J. Paul Duic, MD principal investigator
Long Island Brain Tumor Center at Neurological Surgery PC / Long Island Neuro-Oncology Associates
Jai Grewal, MD principal investigator
Long Island Brain Tumor Center at Neurological Surgery PC/ Long Island Neuro-oncology Associates
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Panobinostat in people with Recurrent Malignant Gliomas, run by Neurological Surgery, P.C. at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 16 Jul 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: insufficient accrual). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To generate preliminary data of anti-tumor efficacy of LBH589 in adults with recurrent malignant gliomas. (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jul 2010.