Pharmacokinetics (PK) Study of AC480 for Recurrent Glioma
The primary objective is to evaluate the intratumoral and plasma pharmacokinetics of AC480 among patients who are candidates for a resection with a recurrent malignant glioma who are not on CYP-3A enzyme inducing anti-epileptic drugs (EIAEDS). Secondary objectives include the following: to evaluate the antiproliferative effect of AC480 by FDG-PET Scan; to evaluate the safety and tolerability of AC480; and, to describe 6-month progression-free survival (PFS) and radiographic response.
This is a single institution, open label, pharmacokinetic study of AC480 in patients with recurrent malignant glioma. The study will enroll 5 patients who are not on enzyme inducing anti-epileptic drugs (EIAEDs) and are scheduled to undergo salvage surgical resection for preoperative treatment with AC480 at 300 mg orally twice daily (BID) for 14 (plus or minus 2) days before surgery (Part I- Induction Therapy). After surgery (Part II- Maintenance Therapy), patients will continue to be dosed with AC480 until disease progression or intolerance, and will be evaluated after every other cycle (1 cycle is 28 days).
|Study Design:||Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Pharmacokinetic Study of AC480 Administered Twice Daily in Surgically Resectable Malignant Glioma Patients Not on Enzyme-Inducing Anticonvulsants|
- Intratumoral and plasma pharmacokinetics of AC480 will be obtained on surgical tissue specimens from 5 patients treated pre-operatively with AC480. [ Time Frame: At time of resection ] [ Designated as safety issue: No ]
- Anti-proliferative effect of AC480 by FDG-PET [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
- Intratumoral and plasma pharmacodynamics of AC480 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
- 6-month progression-free survival (PFS) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
- Radiographic response [ Time Frame: 6 months ] [ Designated as safety issue: No ]
- Adverse event and toxicity monitoring [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
|Study Start Date:||November 2009|
|Study Completion Date:||June 2012|
|Primary Completion Date:||October 2010 (Final data collection date for primary outcome measure)|
Patients who are not on enzyme inducing anti-epileptic drugs (EIAEDs) and are scheduled to undergo salvage surgical resection treated with preoperative AC480 at 300 mg BID followed by post-surgical AC480 at 300 mg BID.
Subjects will be initiated on AC480 300mg orally BID for 14 (+/-2 days) before surgery. After surgery, subjects will continue to be dosed with AC480 until either disease progression or intolerance, and will be evaluated every other cycle (i.e., every 4 weeks).
Plasma and tumoral pharmacokinetics, as well as FDG-PET data will be analyzed to determine the intratumoral and plasma levels of AC480 obtained and its antiproliferative activity. After recovery from surgery, all patients will resume AC480 at 300 mg orally BID until evidence of disease progression or toxicity (Part II: Maintenance Therapy). Those patients will be followed for determination of 6-month progression free survival. Patients will remain on treatment for as long as they have clinical benefit from the treatment. There will be no limit to the number of cycles of treatment a patient can receive providing they continue to benefit from and are not intolerant to AC480 administration.
The data collected in this study will be summarized in tables listing the mean, standard deviation, and number of patients for continuous data, or in tables listing count and percentage for categorical data, where appropriate. All patient data will be listed by patient or by parameter, all statistical analyses will be performed and all data appendices will be created by using the SAS system. Pharmacokinetic analysis will be made to determine if AC480 reaches the intracerebral tumor tissue. Comparisons will be made between the data obtained from the plasma of the same patients treated on AC480, including determination of the tumor-to-plasma ratio. The most common side effects of AC480 are generally mild to moderate in severity and include: nausea, vomiting, diarrhea, fatigue, cough, elevation of the liver enzymes, anemia, and rash.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00979173
|United States, North Carolina|
|The Preston Robert Tisch Brain Tumor Center at Duke University Medical Center|
|Durham, North Carolina, United States, 27710|
|Principal Investigator:||Annick Desjardins, MD, FRCPC||Duke University Health System|