Study of Antineoplaston Therapy + Radiation vs. Radiation Only in Diffuse, Intrinsic, Brainstem Glioma (DIPG)

February 21, 2022 updated by: Burzynski Research Institute

A Randomized Phase 3 Study of Combination Antineoplaston Therapy [Antineoplastons A10 (Atengenal) and AS2-1 (Astugenal)] Plus Radiation Therapy vs. Radiation Therapy Only in Subjects With Newly Diagnosed Diffuse, Intrinsic, Brainstem Glioma

Patients ≥ 3 years of age with newly-diagnosed, diffuse, intrinsic pontine glioma will be enrolled in this study. However, the primary objectives of this study are to 1) compare overall survival, the time from randomization to death from any cause, for study subjects 3-21 years of age with newly-diagnosed, diffuse, intrinsic pontine glioma who receive Antineoplaston therapy (Atengenal + Astugenal) + radiation therapy vs. radiation therapy alone and 2) describe the toxicity profile (all subjects) for Antineoplaston therapy + radiation therapy vs. radiation therapy alone.

A secondary objective is to compare progression-free survival for study subjects 3-21 years of age with newly-diagnosed, diffuse, intrinsic pontine glioma treated with Antineoplaston therapy + radiation therapy vs. radiation therapy alone.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a randomized Phase 3 protocol study of Antineoplaston therapy + radiation therapy vs. radiation therapy alone in subjects ≥ 3 years of age with newly-diagnosed, diffuse, intrinsic pontine glioma. In those subjects randomized to Antineoplaston therapy + radiation therapy, Antineoplaston therapy is administered for 104 weeks while radiation therapy commences on day one of Antineoplaston therapy and continues for 6 weeks. Subjects continue on Antineoplaston therapy if an objective response or stable disease is achieved during therapy and are maintained on Antineoplaston therapy to the end of the protocol study unless they develop progressive disease. Subjects randomized to radiation therapy alone receive 6 weeks of radiation therapy.

Exploratory objectives are to compare the following in the two treatment arms: 1) overall survival for study subjects ≥ 21 years of age; 2) progression-free survival for subjects ≥ 21 years of age; 3) objective response, complete response, partial response, and progressive disease rates, based on the enhancing portion of the tumor, for all subjects, using bidimentional measurement of tumor; 4) objective response, complete response, partial response, and progressive disease rates, for all subjects with non-enhancing tumors, using unidimentional measurement of tumor; and 5) objective response, complete response, partial response, and progressive disease rates, based on the enhancing + non-enhancing portions of the tumor, for all subjects, using unidimentional measurement of tumor.

Study Type

Interventional

Enrollment (Anticipated)

92

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

3 years to 99 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Subjects with Diffuse, Intrinsic Pontine Glioma as defined by the following criteria are eligible:

    • A characteristic MRI appearance, including variable contrast enhancement after gadolinium administration, diffuse T2/FLAIR signal, and involvement of more than 50% of the pons.
    • Confirmation of anaplastic glioma (i.e., oligodendroglioma, astrocytoma, oligoastrocytoma) or GBM histology if there is less than 50% involvement of the pons.
  • Screening evaluation requires a MRI performed within 14 days prior to the start of ANP therapy. Study subjects must be on a fixed dose of steroids for at least five days prior to the screening MRI. If the steroid dose is changed between the date of imaging and the start of treatment, a new baseline MRI is required. All MRIs must be performed at an accredited radiology center. All MRIs should include at a minimum: T1-weighted images pre/post gadolinium administration, fluid attenuated inversion recovery (FLAIR), and T-2 weighted images.
  • Subjects 3-21 years of age must have a clinical history of disease of less than 6 months and at least two of the following clinical findings: cranial nerve deficit, long tract signs (i.e. hemiparesis) and ataxia are eligible. Subjects > 21 years of age do not need to meet these criteria.
  • Subjects must be ≥ 3 years of age. RT is not recommended for subjects less than 3 years of age.
  • Subjects ≤ 16 years of age with a Lansky performance status of > 40 are eligible. Subjects > 16 years of age with a Karnofsky performance status of > 40 are eligible.

  • Subjects with organ and marrow function (as defined below) are eligible.

    • Hemoglobin ≥ 9 g/dL
    • Leukocytes > 2000/mm3
    • Absolute neutrophil count >1,000/ mm3
    • Serum Na+ ≤ 150 mmol/L
    • Serum K+ ≤ 5.5 mmol/L
    • Serum creatinine ≤ 1.5 times institutional upper limit
    • Platelets >50,000/ mm3
    • Total bilirubin < 2.5 mg/dL
    • AST (SGOT) / ALT (SGPT) <5 times institutional upper limit
  • At the recommended therapeutic dose, the effects of ANP therapy on the developing human fetus are unknown. For this reason, women of child-bearing potential who agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to protocol study entry and for the duration of the protocol study are eligible. Should a woman become pregnant or suspect she is pregnant while participating in this protocol study, she will inform her treating physician immediately.
  • Subjects, parents, and/or guardians who are able to understand a written informed consent document, and are willing to sign it, are eligible.

Exclusion Criteria:

  • No type of prior therapy, including other investigational agents, is allowable. A prior diagnostic biopsy or surgical shunt for hydrocephalus is permitted.
  • Subjects with disseminated disease, multicentric tumors, leptomeningeal disease, or the history of retrotumoral bleeding are not eligible. The screening / baseline MRI includes the spinal cord to rule out leptomeningeal disease.
  • Subjects with a known history of ganglioglioma are not eligible.
  • Subjects with a current diagnosis or family history of neurofibromatosis I or II are not eligible. - Subjects with a current diagnosis or family history of neurofibromatosis are not eligible.
  • Subjects with an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, uncontrolled hypertension despite maximal medical management (three supine blood pressure measurements ≥ 150/99 taken at least one hour apart) or psychiatric illness/social situations that would limit compliance with protocol study requirements are not eligible.
  • Subjects with a history of New York Heart Association Class II congestive heart failure are not eligible.
  • Pregnant women are not eligible because the teratogenic and abortifacient effects of ANP therapy in humans are unknown. Because there is an unknown but potential risk for adverse events in nursing infants secondary to the mother receiving ANP therapy, breastfeeding is discontinued if the mother receives ANP therapy.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Radiation
Study subjects receive a single daily radiation fraction of 180cGy, 5 days a week for 6 weeks overall, to a total radiation dose of 5400cGy.
Radiation: Radiation
Subjects ≥ 3 years of age with a diffuse, intrinsic brain stem glioma will receive radiation.
Experimental: Antineoplaston therapy + Radiation
Antineoplaston therapy (Atengenal + Astugenal) by IV infusion every four hours for 104 weeks. 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 6 weeks overall, to a total radiation dose of 5400cGy.
Radiation: Radiation
Subjects ≥ 3 years of age with a diffuse, intrinsic brain stem glioma will receive radiation.
Drug: Atengenal
Subjects ≥ 3 years of age with a diffuse, intrinsic brain stem glioma will receive Atengenal in combination with Astugenal (Antineoplaston therapy) and radiation
Other Names:
  • A10
Drug: Astugenal
Subjects ≥ 3 years of age with a diffuse, intrinsic brain stem glioma will receive Astugenal in combination with Atengenal (Antineoplaston therapy) and radiation
Other Names:
  • AS2-1

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Percentage of Participants Who Survived (Overall Survival)
Time Frame: 6 months, 12 months, 24 months, 36 months, 48 months, 60 months
The Kaplan-Meier nonparametric method is used to evaluate overall survival in the two therapy groups. Survival difference is evaluated using a log-rank test, which compares the two therapy groups. A Cox proportional hazards model is used as a supportive analysis to assess the magnitude of difference between the two therapy groups. The median survival rate in the two therapy groups (and 95% confidence intervals) is evaluated. Hazard ratio and its 95% confidence interval are estimated.
6 months, 12 months, 24 months, 36 months, 48 months, 60 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Percentage of Participants Who Survived (Progression-free Survival)
Time Frame: 6 months, 12 months, 24 months, 36 months, 48 months, 60 months
The Kaplan-Meier nonparametric method is used to evaluate progression-free survival in the two therapy groups. Progression-free survival difference is evaluated using a log-rank test, which compares the two therapy groups. A Cox proportional hazards model is used as a supportive analysis to assess the magnitude of difference between the two therapy groups. The median progression-free survival rate in the two therapy groups (and 95% confidence intervals) is evaluated. Hazard ratio and its 95% confidence interval are estimated.analysis is provided.
6 months, 12 months, 24 months, 36 months, 48 months, 60 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Burzynski Research Institute

Investigators

  • Study Chair: Stanislaw R. Burzynski, MD, PhD, Burzynski Research Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

June 1, 2024

Primary Completion (Anticipated)

June 1, 2026

Study Completion (Anticipated)

June 1, 2026

Study Registration Dates

First Submitted

August 9, 2016

First Submitted That Met QC Criteria

August 29, 2016

First Posted (Estimate)

September 1, 2016

Study Record Updates

Last Update Posted (Actual)

February 22, 2022

Last Update Submitted That Met QC Criteria

February 21, 2022

Last Verified

February 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BRI-BT-52

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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