A Safety Study of RTA 744 in Patients With Recurrent High-Grade Gliomas
This study assesses the tolerability, safety, efficacy and pharmacokinetics of RTA 744 in recurrent high-grade gliomas.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Dose-finding and Pharmacokinetic Study of Intravenous RTA 744 Injection in Patients With Recurrent or Refractory Anaplastic Astrocytoma (AA), Anaplastic Oligodendroglioma (AO), Anaplastic Mixed Oligo-astrocytoma (AOA), Glioblastoma Multiforme (GBM) or Gliosarcoma (GS), With or Without Concurrent Treatment With Enzyme-inducing Anticonvulsant Therapy|
- To determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of RTA 744 Injection in the patient population studied and to determine the qualitative and quantitative toxic effects of RTA 744 Injection. [ Time Frame: at end of first cycle for each patient cohort ] [ Designated as safety issue: Yes ]
- To characterize the multiple-dose pharmacokinetics of RTA 744 and to document any potential antitumor activity of RTA 744 in those patients with measurable disease. [ Time Frame: end of study ] [ Designated as safety issue: No ]
|Study Start Date:||November 2005|
|Primary Completion Date:||December 2008 (Final data collection date for primary outcome measure)|
Experimental: Group A (RTA 744)
Receive study drug for three consecutive days, Cycle repeated every 21 days.
Drug: RTA 744
Aqueous solution added to 10%D/W and infused over 2 hours on three consecutive days. 5 mg vials contain 1 mg/ml.
Experimental: Group C (RTA 744 Injection)
Receive study drug once a week for four consecutive weeks. Repeat cycle every 5 weeks.
Drug: RTA 744 injection
Aqueous solution in 1mg/ml. Doses are escalated. Drug is infused intravenously over 2 hours one day a week for four consecutive weeks.
Malignant gliomas, glioblastoma multiforme and anaplastic astrocytoma, are rapidly growing primary brain tumors associated with a high degree of morbidity and mortality. Despite aggressive treatment, the median survival rate for GBM is approximately 12 months, with two-year survival rates no more than 8 to 12%, while median survival for patients with AA ranges from 2 to 3 years from time of first diagnosis.
RTA 744 is a close chemical analogue of the well characterized anti-cancer agent doxorubicin. Unlike doxorubicin, RTA 744 has shown ability to cross the blood brain barrier and to achieve high concentration in CNS tumor tissue in animal models. It will be administered by i.v. infusions either daily for 3 consecutive days repeated every three weeks, or once weekly for 4 consecutive weeks repeated every 5 weeks. Once the maximum tolerated dose is determined , a new group of patients will be enrolled into the study to evaluate the tolerability and MTD when administered on an expanded schedule (once a week).
Please refer to this study by its ClinicalTrials.gov identifier: NCT00526812
|United States, California|
|UCLA School of Medicine, Department of Neurology|
|Los Angeles, California, United States, 90095|
|United States, Texas|
|Baylor University Medical Center: Neuro-Oncology Associates|
|Dallas, Texas, United States, 75246|
|University of Texas Southwestern Medical Center|
|Dallas, Texas, United States, 75309|
|The University of Texas M. D. Anderson Cancer Center|
|Houston, Texas, United States, 77030|