A Panobinostat Presurgery (CLBH589C)
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.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Study of Panobinostat (LBH589) for Recurrent Glioblastoma (GBM) Undergoing Planned Surgical Resection|
- Anti-tumor Activity as Measured by Percentage of Patients Who Remain Progression-free after Six Months [ Time Frame: 18 months ] [ Designated as safety issue: No ]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)
- Safety Evaluation of Panobinostat [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]A secondary objective is to further evaluate the safety of panobinostat in recurrent GBM patients
- Evaluation of Intratumoral Pharmacokinetics and Pharmacodynamics of Panobinostat [ Time Frame: 24 months ] [ Designated as safety issue: No ]A secondary objective is to evaluate the intratumoral pharmacokinetics and pharmacodynamics of panobinostat among recurrent GBM patients scheduled for surgical debulking
- Evaluation of Systemic Pharmacokinetics [ Time Frame: 24 months ] [ Designated as safety issue: No ]A secondary objective is to evaluate the systemic pharmacokinetics of panobinostat among recurrent GBM patients.
|Study Start Date:||April 2010|
|Estimated Study Completion Date:||April 2012|
|Estimated Primary Completion Date:||April 2011 (Final data collection date for primary outcome measure)|
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.
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.
|United States, North Carolina|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27710|
|Principal Investigator:||David A Reardon, MD||Duke University|