Effect of Antineoplaston Therapy on the QT/QTc Interval In Subjects With Diffuse, Intrinsic, Brainstem Glioma

Study Overview
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Brief Summary
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The primary objective of this protocol study is to investigate the effect of Antineoplaston therapy on the QT/QTc interval in study subjects age 3 to 21 years with newly-diagnosed, diffuse, intrinsic brainstem glioma. This investigation is to be conducted in parallel with a phase 3 efficacy and safety study of combination Antineoplaston therapy + radiation vs. radiation alone (BRI-BT-52).

Detailed Description
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QT/QTc interval prolongation is investigated during the first two weeks of subject participation in the parallel phase 3 study. The pre-cordial leads and lead II will be utilized to determine QT/QTc prolongation. Descriptive information is provided on changes in T and U wave morphologies. The percentage of subjects in each therapy group who have worsening of the T and U wave morphology is documented. Discrete U waves are excluded from the QT/QTc interval measurement. Except for the pre-therapy ECGs, all ECGs are performed during one ANP therapy infusion daily, that being an afternoon infusion to account for diurnal variation in the QT/QTc interval. The study subject is at rest in the supine position for 30 minutes prior to the ECG study. The baseline QTc is derived from 3 ECGs taken on day 1 during the hour preceding the first Antineoplaston therapy infusion or the first radiation session.

Official Title
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A Controlled, Study of the Effect of Combination Antineoplaston Therapy [Atengenal (A10) and Astugenal (AS2-1)] on the QT/QTc Interval In Subjects With Newly Diagnosed Diffuse, Intrinsic, Brainstem Glioma

Conditions
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Brain Stem Glioma

Intervention / Treatment
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* Radiation: Radiation
* Drug: Atengenal
* Drug: Astugenal


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Enrolled in BRI-BT-52 Exclusion Criteria: Not enrolled in BRI-BT-52

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Radiation<br>Study subjects receive a single daily radiation fraction of 180cGy, 5 days a week, for the 2 weeks of the QT/QTc study and for 6 weeks overall to a total radiation dose of 1600 cGy and 5400cGy, respectively. | Radiation: Radiation<br>* Children with a diffuse, intrinsic brain stem glioma will receive radiation.<br>|
| Experimental: Antineoplaston therapy + Radiation<br>Antineoplaston therapy (Atengenal + Astugenal) by IV infusion every four hours for at least 24 months. Study subjects receive increasing dosages of Atengenal and Astugenal until the maximum tolerated dose is reached.Study subjects also receive a single daily radiation fraction of 180cGy, 5 days a week, for the 2 weeks of the QT/QTc study and for 6 weeks overall to a total radiation dose of 1600 cGy and 5400cGy, respectively. | Radiation: Radiation<br>* Children with a diffuse, intrinsic brain stem glioma will receive radiation.<br>Drug: Atengenal<br>* Children with a diffuse, intrinsic brain stem glioma will receive Atengenal in combination with Astugenal (Antineoplaston therapy) and radiation<br>* Other names: A10;Drug: Astugenal<br>* Children with a diffuse, intrinsic brain stem glioma will receive Astugenal in combination with Atengenal (Antineoplaston therapy) and radiation<br>* Other names: AS2-1;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with an Increase in the QTc interval | The mean maximum increase in QTc interval, as determined by repeated ECGs, for the Antineoplaston therapy + Radiation study group and the Radiation only study group. | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with Alterations in T and U Wave Morphology | Alterations in T and U wave morphology, as determined by repeated ECGs, for the Antineoplaston therapy + Radiation study group and the Radiation only study group. | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diffuse, intrinsic brain stem glioma, QT/QTc interval, Radiation, Antineoplaston therapy