In the current study, the investigators will evaluate intratumoral pharmacodynamic and pharmacokinetic data associated with the administration of the HDACI, Panobinostat, among recurrent GBM patients. In addition, this study will evaluate the safety and tolerability of this agent, as well as evidence of anti-tumor activity in the patient population.
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 investigator.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Oral panobinostat will be administered at 20mg by mouth 3 times a week one week prior to surgical resection. Within 2-6 weeks of resection, patients will resume panobinostat at 20mg 3 times per week. A cycle will be 28 days.
Duke University Medical Center
Durham, North Carolina, United States
Anti-tumor Activity as Measured by Percentage of Patients Who Remain Progression-free after Six Months
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)
Time frame: 18 months
Safety Evaluation of Panobinostat
A secondary objective is to further evaluate the safety of panobinostat in recurrent GBM patients
Time frame: 24 months
Evaluation of Intratumoral Pharmacokinetics and Pharmacodynamics of Panobinostat
A secondary objective is to evaluate the intratumoral pharmacokinetics and pharmacodynamics of panobinostat among recurrent GBM patients scheduled for surgical debulking
Time frame: 24 months
Evaluation of Systemic Pharmacokinetics
A secondary objective is to evaluate the systemic pharmacokinetics of panobinostat among recurrent GBM patients.
Time frame: 24 months
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