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Study Summary
No. 2005-0188:.......Brain; CNS......Charles A. Conrad......Neuro Oncology
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Study Summary Title
Study Summary
Number:
2005-0188
Study 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 Drug Therapy.
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Physician New Patient Referral
Name:Charles A. ConradPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Neuro OncologyReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-792-2883
Contact us about clinical trials
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General Information
Disease Group:Brain
CNS
Supported By:N/A
Phase of Study:Phase IReturn
Visit:
3 days every 3 weeks
Treatment
Agents:
RTA 744Home Care:None
Treatment Loc:Independent Multicenter Arrangements
Estimated
Length of Stay
in Houston:
None
Description/
Intervention:
The goal of this clinical research study is to find the highest safe dose of
RTA 744 that can be given to patients with primary brain tumors. The effect
of RTA 744 on brain tumor cells and the effect of giving RTA 744 with
anti-epilepsy medications will also be studied.
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Study Objectives / Outcomes
Primary Objectives:

· To determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of 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).
· To determine the qualitative and quantitative toxic effects of RTA 744 Injection and to study the predictability, duration, intensity, onset, reversibility and dose-relationship of the toxic side effects.
· To characterize these two primary objectives in: a) patients who are not receiving enzyme inducing anticonvulsant drugs and will receive RTA 744 administered daily x 3 every 21 days in (Group A); b) patients who are receiving concurrent enzyme-inducing anti-convulsant drugs and will receive RTA 744 administered daily x 3 every 21 days (Group B); and c) in patients who are not receiving enzyme inducing anticonvulsant drugs and will receive RTA 744 administered once weekly for 4 weeks repeated every 5 weeks (Group C).

Secondary Objectives:

· To characterize the multiple-dose pharmacokinetics of RTA 744 in patients enrolled into Group A, Group B and Group C as described in the primary objectives;
· To document any potential antitumor activity of RTA 774 in those patients with measurable disease.
· To correlate pharmacokinetic information with clinical (efficacy and safety) responses, as a possible help in selecting appropriate doses for later studies.
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Study Status Information
Study Activation / Registration Date:09/08/2005
IRB Review and Approval Date:06/01/2005
Study Type:Therapeutic
Recruitment Status:Terminated
Projected Accrual:65
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:1) Age >/= 18 years.

2) Prior histologically confirmed anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic mixed oligo-astrocytoma, glioblastoma multiforme, or gliosarcoma, who do not have any other effective therapy available to them. (Patients may have received any number of other chemotherapies prior to entry into this study.)

3) 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.

4) Unequivocal evidence of recurrence or progression by neuroimaging procedure.

5) If patient had surgical resection prior to enrollment, at least 2 weeks should have elapsed prior to enrollment into the study and patient must have completely recovered from the side effects of such therapy.

6) Patients should be on a stable dose of steroids for at least 7 days prior to obtaining the Gd-MRI of the brain, if medically feasible.

7) Patients with previously implanted Gliadel® wafer may be eligible after discussion with the principal investigator regarding evidence of disease progression, provided that Gliadel was implanted at least 6 week prior to study entry.

8) Karnofsky Performance Status (KPS) of >/= 60.

9) Laboratory parameters: (a) Absolute Neutrophil Count (ANC) >/= 1.5 x 10^9/L; (b) Hemoglobin (Hgb) >/= 9 g/dl; (c) Platelets >/= 100 x 10^9/L; (d) AST and ALT </= 3.0 x Upper Limit of Normal (ULN); (e) Serum bilirubin </= 1.5 x ULN; (f) Serum creatinine </= 1.5 x ULN and 24 hour creatinine clearance >/= 50 ml/min.

10) Life expectancy of greater than 12 weeks.

11) Written informed consent obtained.

Exclusion Criteria:1) Patients who are pregnant or breast feeding, or adults of reproductive potential not employing an effective method of birth control (such as oral, implantable, or injectable contraceptives). (Women of childbearing potential must have a negative serum pregnancy test 72 hours prior to administration of RTA 744 Injection).

2) Total urinary protein in 24 hours urine collection > 500 mg.

3) Any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study: (a)uncontrolled diabetes (patients diagnosed with Type 1 or Type 2 diabetes who are currently under treatment by a physician for this condition and are not able to control blood sugars with management for glucose levels above 250 mgs. per deciliter); (b)active or uncontrolled infection; (c)acute or chronic liver disease, (i.e., hepatitis, cirrhosis); or (d)confirmed diagnosis of HIV infection

4) Impaired cardiac function, major prior cardiac disease or arrhythmia: a) LVEF< 45 % as determined by MUGA scan/ECG; b) complete left bundle branch block; c) obligate use of a cardiac pacemaker; d) ST depression of >1mm in >/=2 leads and/or T wave inversions in >/=2 contiguous leads; e) congenital long QT syndrome; f) history/presence of ventricular/atrial tachyarrhythmias; g) clinically significant resting bradycardia (<50 bts/min); h) QTc >480 msec on screening ECG; i) uncontrolled high blood pressure, history of labile hypertension or of poor compliance with an antihypertensive regimen.

5) Patients with history of CHF or arrhythmias.

6) Patients who are taking therapeutic doses of warfarin sodium (Coumadin®).

7) Patients who have received the following types of prior or concurrent therapy, ow who have not recovered from the toxic effects of such therapy: (1) investigatonal drugs less than 4 weeks prior to entry on this study; (2) chemotherapy within 4 weeks prior (6 weeks for notrosourea or mitomycin-c or 2 weeks for vincristine) to entry on this study; (3) metronomic daily dosing of chemotherapy agents - patients may be enrolled 1 week after discontinuation of these agents as long as ANC returns to 1.0 x 10^9/L and platelet count returns to >/= 100,000;

8) Continued from # 7: (4) biologic, immunotherapy or cytostatic agents within 4 weeks prior to study entry;(5) radiation therapy within 2 weeks prior to entry on this study; (6) any medication known to cause QT interval prolongation.

9) Patients who have had any surgery other than resection of a brain tumor within 2 weeks prior to entry on this study.

10) Patient unwilling to or unable to comply with the protocol.

11) Patients who have a contraindication to MRI imaging (cardiac pacemaker, other ferromagnetic metal implants, claustrophobia not amenable to conscious sedation, and obesity greater than 300 lbs).

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Links
Registration Number: NCT00526812
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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