A Phase I Trial of Nanoliposomal CPT-11 (NL CPT-11) in Patients With Recurrent High-Grade Gliomas
This is a Phase I study of Nanoliposomal CPT-11 in patients with Recurrent high-grade gliomas. Patients must have a histologically proven intracranial malignant glioma, which includes glioblastoma multiforme (GBM), gliosarcoma (GS), anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), anaplastic mixed oligoastrocytoma (AMO), or malignant astrocytoma NOS (not otherwise specified). Patients who are wild type or heterozygous for the UGT1A1*28 gene will received Nanoliposomal CPT-11. The total anticipated accrual will be approximately 36 patients (depending upon the actual MTD). The investigators hypothesis is that this new formulation of CPT-11 will increase survival over that seen in historical controls who have recurrent gliomas because CPT-11 will be encapsulated in a liposome nanoparticle, which has been seen to reduce toxicities from the drug.
Drug: Nanoliposomal CPT-11
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Trial of Nanoliposomal CPT-11 (NL CPT-11) in Patients With Recurrent High-Grade Gliomas|
- To assess the safety and pharmacokinetics of NL CPT-11 in patients with recurrent malignant glioma stratified based on UGT1A1 genotyping. [ Time Frame: 1-2 years ] [ Designated as safety issue: Yes ]
- To determine the maximum tolerated dose of NL CPT-11 in these patient populations. [ Time Frame: 1-2 years ] [ Designated as safety issue: Yes ]
|Study Start Date:||August 2008|
|Study Completion Date:||December 2014|
|Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
Experimental: Nanoliposomal CPT-11
All patients are treated with nanoliposomal CPT-11
Drug: Nanoliposomal CPT-11
Depending on UGT1A1 genotyping status, patients are either given a starting dose of 120 mg/m^2 (wild type) or 60 mg/m^2 IV q3 weeks.
Patients with recurrent malignant glioma will receive Nanoliposomal CPT-11 at the time of relapse. The dose will be adjusted according to a phase-1 dose escalation scheme. Patients will receive drug intravenously every 3 weeks until tumor progression or excessive toxicity. Weekly follow up will occur to assess toxicities during the DLT phase of the trial. Patients will have different dose escalation if UGT1A1 is 6/6 versus UGT1A1 is 6/7. Patients with UGT 1A1 of 7/7 will not be eligible. All patients must have UGT 1A1 status know as an eligibility requirement. Patients will be followed for both toxicity and progression, and progression will be evaluated by MR imaging every 6 weeks. Pharmacokinetics will be obtained in the first treatment cycle.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00734682
|United States, California|
|University of California, San Francisco|
|San Francisco, California, United States, 94143|
|Principal Investigator:||Michael Prados, MD||University of California, San Francisco|