A Safety Study of RTA 744 in Patients With Recurrent High-Grade Gliomas - Full Text View

Sponsored by:	Reata Pharmaceuticals, Inc.
Information provided by:	Reata Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:	NCT00526812

Purpose

This study assesses the tolerability, safety, efficacy and pharmacokinetics of RTA 744 in recurrent high-grade gliomas.

Condition	Intervention	Phase
Glioma	Drug: RTA 744 Drug: RTA 744 injection	Phase I

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
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

Further study details as provided by Reata Pharmaceuticals, Inc.:

Primary Outcome Measures:

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 ]

Secondary Outcome Measures:

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 ]

Estimated Enrollment:	50
Study Start Date:	November 2005
Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Group A: Experimental 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.
Group C: Experimental 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.

Detailed Description:

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).

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Prior histologically confirmed anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic mixed oligo-astrocytoma, glioblastoma multiforme, or gliosarcoma, for whom no other effective therapy is available.
A prior histologic diagnosis of a lower grade of glioma is allowed if there is current histologic proof of progression to a diagnosis of AA, AO, AOA, GBM or GS
Unequivocal evidence of recurrence or progression by neuroimaging procedure.
Surgical resection at least 2 weeks prior to enrollment and must have completely recovered from the side effects.
A stable dose of steroids for at least 7 days prior to obtaining the Gd-MRI of the brain.
Previously implanted Gliadel® wafer may be eligible.
Karnofsky Performance Status (KPS) of ≥ 60.
Laboratory parameters: Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L, Hemoglobin (Hgb) ≥ 9 g/dl, Platelets ≥ 100 x 109/L, AST and ALT ≤ 3.0 x Upper Limit of Normal (ULN), Serum bilirubin ≤ 1.5 x ULN, Serum creatinine ≤ 1.5 x ULN and 24 hour creatinine clearance ≥ 50 ml/min
Life expectancy of greater than 12 weeks.
Written informed consent obtained.

Exclusion Criteria:

Pregnancy or breast feeding, or adults of reproductive potential not employing an effective method of birth control
Total urinary protein in 24 hours urine collection > 500 mg
Any concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study.
Impaired cardiac function, other significant prior cardiac disease or arrhythmia of any
A history of CHF or arrhythmias.
Therapeutic doses of warfarin sodium (Coumadin®).
Prior or concurrent therapy, or not recovered from the toxic effects of such therapy: investigational drugs, chemotherapy, metronomic daily dosing of chemotherapy agents, biologic, immunotherapy or cytostatic agents within 4 weeks prior to study entry; radiation therapy within 2 weeks prior to study entry, any medication known to cause QT interval prolongation
Any surgery other than resection of a brain tumor within 2 weeks prior to enrollment.
A contraindication to MRI imaging.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00526812

Locations

United States, California
UCLA School of Medicine, Department of Neurology
Los Angeles, California, United States, 90095
United States, Texas
The University of Texas M. D. Anderson Cancer Center
Houston, Texas, United States, 77030
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75309
Baylor University Medical Center: Neuro-Oncology Associates
Dallas, Texas, United States, 75246

Sponsors and Collaborators

Reata Pharmaceuticals, Inc.

More Information

Responsible Party:	Reata Pharmaceuticals, Inc
Study ID Numbers:	RTA 744-C-0401
Study First Received:	September 7, 2007
Last Updated:	December 19, 2008
ClinicalTrials.gov Identifier:	NCT00526812
Health Authority:	United States: Food and Drug Administration

Study placed in the following topic categories:

Neuroectodermal Tumors
Signs and Symptoms
Glioblastoma
Glioblastoma multiforme
Astrocytoma
Neoplasms, Germ Cell and Embryonal

Neuroepithelioma
Oligodendroglioma
Glioma
Gliosarcoma
Recurrence
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial

ClinicalTrials.gov processed this record on January 14, 2009