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Phase II Study of Panobinostat (LBH589) for Recurrent Glioblastoma (GBM) Undergoing Planned Surgical Resection

Phase 2
18 Years
Not Enrolling
Recurrent Glioblastoma

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Trial Information

Phase II Study of Panobinostat (LBH589) for Recurrent Glioblastoma (GBM) Undergoing Planned Surgical Resection

This study will enroll a maximum of 24 subjects with recurrent GBM who are scheduled for
planned debulking craniotomy.

After screening and enrollment on the study, subjects will receive 20mg panobinostat 3 times
a week for one week prior to surgery. Within 2-6 weeks of resection, subjects will resume
panobinostat at 20mg panobinostat 3 times per week.

The primary endpoint will be 6-month progression-free survival. Each cycle of therapy will
be 28 days. All subjects will be assessed after every other cycle of therapy. Subjects will
remain on study therapy for at least one year unless they develop progressive disease,
unacceptable toxicity, non-compliance with study procedures or withdraw consent. Patients
may continue treatment with oral panobinostat until they experience unacceptable toxicity
that precludes further treatment, disease progression, and/or at the discretion of the

Inclusion Criteria:

- Patient age is ≥ 18 years

- Histologically-confirmed grade 4 malignant glioma patients;

- Candidate for surgical resection of tumor;

- No more than 3 prior episodes of progressive disease;

- An interval of at least 4 weeks between prior surgical resection or two weeks from
stereotactic biopsy;

- An interval of at least 12 weeks from the end of prior radiotherapy unless there is a
new area of enhancement consistent with recurrent tumor outside of the radiation
field, or there are progressive changes on MRI on at least two consecutive MRI scans
at least four weeks apart, or there is biopsy-proven tumor progression;

- An interval of at least 4 weeks from prior chemotherapy (6 weeks for nitrosoureas) or
investigational agent, unless the patient has recovered from all anticipated
toxicities associated with that therapy;

- Karnofsky * 70%;

- Hemoglobin ≥ 9 g/dL, ANC > 1,500 cells/*l, platelets > 150,000 cells/*l ;

- Serum creatinine < 1.5 mg/dl or 24-hour creatinine clearance ≥ 50 ml/min, serum SGOT
and bilirubin < 1.5 times upper limit of normal; total serum calcium (corrected for
serum albumin) or ionized calcium ≥ LLN; serum potassium ≥ LLN; serum sodium ≥ LLN;
serum albumin ≥ LLN or 3g/dl;

- Clinically euthyroid (Note: Patients are permitted to receive thyroid hormone
supplements to treat underlying hypothyroidism);

- Baseline MUGA or ECHO must demonstrate LVEF ≥ the lower limit of the institutional

- Ability to provide written informed consent obtained prior to participation in the
study and any related procedures being performed;

Exclusion Criteria:

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

- Patients who will need valproic acid for any medical condition during the study or
within 5 days prior to first panobinostat treatment;

- Use of CYP-3A inducing anti-epileptics (phenytoin, fosphenytoin, carbamazepine,
oxcarbazepine, phenobarbitol, primidone);

- Pregnancy or breast feeding;

- Co-medication that may interfere with study results; e.g. immuno-suppressive agents
other than corticosteroids;

- Active infection requiring intravenous antibiotics;

- Prior bevacizumab within 6 weeks of study enrollment;

- Therapeutic anti-coagulation with warfarin, aspirin, non-steroidal anti-inflammatory
drugs or clopidogrel;

- Impaired cardiac function including any one of the following:

- Complete left bundle branch block or use of a permanent cardiac pacemaker,
congenital long QT syndrome, history or presence of ventricular
tachyarrhythmias, clinically significant resting bradycardia (<50 beats per
minute), QTcF > 450 msec on screening ECG, or right bundle branch block + left
anterior hemiblock (bifascicular block);

- Presence of atrial fibrillation (ventricular heart rate >100 bpm);

- Previous history angina pectoris or acute MI within 6 months;

- Congestive heart failure (New York Heart Association functional classification
III-IV) or baseline MUGA/Echo shows LVEF < 45%;

- Uncontrolled hypertension;

- Concomitant use of drugs with a risk of causing Torsades de pointes (See Table 14-1);

- Patients with unresolved diarrhea ≥ grade 2;

- Patients with ≥ grade 2 peripheral neuropathy;

- Impairment of gastrointestinal (GI) function or GI disease that may significantly
alter the absorption of oral panobinostat (e.g., ulcerative disease, uncontrolled
nausea, vomiting, diarrhea, malabsorption syndrome, obstruction, or stomach and/or
small bowel resection)

- Other concurrent severe and/or uncontrolled medical conditions;

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

- Patients with a history of another primary malignancy within 5 years other than
curatively treated carcinoma in situ of the cervix, or basal or squamous cell
carcinoma of the skin;

- Patients with known positivity for human immunodeficiency virus (HIV) or hepatitis C;
baseline testing for HIV and hepatitis C is not required;

- Patients with any significant history of non-compliance to medical regimens or with
inability to grant a reliable informed consent.

- 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. WOCBP are defined as sexually
mature women who have not undergone a hysterectomy or who have not been naturally
postmenopausal for at least 12 consecutive months (i.e., who has had menses any time
in the preceding 12 consecutive months). Women of childbearing potential (WOCBP)
must have a negative serum pregnancy test within 7 days of the first administration
of oral panobinostat;

- 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.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Anti-tumor Activity as Measured by Percentage of Patients Who Remain Progression-free after Six Months

Outcome Description:

The primary objective will be to determine the anti-tumor activity of panobinostat among recurrent GBM patients as measured by the percentage of patients who remain progression-free after 6 months of therapy (PFS-6)

Outcome Time Frame:

18 months

Safety Issue:


Principal Investigator

David A Reardon, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Duke University


United States: Food and Drug Administration

Study ID:




Start Date:

April 2010

Completion Date:

April 2012

Related Keywords:

  • Recurrent Glioblastoma
  • glioblastoma
  • recurrent
  • surgical resection
  • Glioblastoma



Duke University Medical CenterDurham, North Carolina  27710