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

Primary Purpose

Glioma

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

RTA 744

RTA 744 injection

About this trial

This is an interventional treatment trial for Glioma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

UCLA School of Medicine, Department of Neurology
Baylor University Medical Center: Neuro-Oncology Associates
University of Texas Southwestern Medical Center
The University of Texas M. D. Anderson Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Group A (RTA 744)

Group C (RTA 744 Injection)

Arm Description

Receive study drug for three consecutive days, Cycle repeated every 21 days.

Receive study drug once a week for four consecutive weeks. Repeat cycle every 5 weeks.

Outcomes

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.

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.

Full Information

NCT ID

NCT00526812

First Posted

September 7, 2007

Last Updated

November 5, 2014

Sponsor

Reata Pharmaceuticals, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT00526812

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2014

Overall Recruitment Status

Completed

Study Start Date

November 2005 (undefined)

Primary Completion Date

December 2008 (Actual)

Study Completion Date

undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Reata Pharmaceuticals, Inc.

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Glioma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

54 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Group A (RTA 744)

Arm Type

Experimental

Arm Description

Receive study drug for three consecutive days, Cycle repeated every 21 days.

Arm Title

Group C (RTA 744 Injection)

Arm Type

Experimental

Arm Description

Receive study drug once a week for four consecutive weeks. Repeat cycle every 5 weeks.

Intervention Type

Drug

Intervention Name(s)

RTA 744

Intervention Description

Aqueous solution added to 10%D/W and infused over 2 hours on three consecutive days. 5 mg vials contain 1 mg/ml.

Intervention Type

Drug

Intervention Name(s)

RTA 744 injection

Intervention Description

Aqueous solution in 1mg/ml. Doses are escalated. Drug is infused intravenously over 2 hours one day a week for four consecutive weeks.

Primary Outcome Measure Information:

Title

Time Frame

at end of first cycle for each patient cohort

Secondary Outcome Measure Information:

Title

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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.

Facility Information:

Facility Name

UCLA School of Medicine, Department of Neurology

City

Los Angeles

State/Province

California

ZIP/Postal Code

90095

Country

United States

Facility Name

Baylor University Medical Center: Neuro-Oncology Associates

City

Dallas

State/Province

Texas

ZIP/Postal Code

75246

Country

United States

Facility Name

University of Texas Southwestern Medical Center

City

Dallas

State/Province

Texas

ZIP/Postal Code

75309

Country

United States

Facility Name

The University of Texas M. D. Anderson Cancer Center

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

12. IPD Sharing Statement

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

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