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

Phase

Condition

Brain Tumor

Astrocytoma

Neurofibromatosis

Treatment

Radiation

Astugenal

Atengenal

Clinical Study ID

NCT02887040

BRI-BT-52

Ages 3-99
All Genders

Study Summary

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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

Subjects with Diffuse, Intrinsic Pontine Glioma as defined by the following criteriaare eligible:
A characteristic MRI appearance, including variable contrast enhancement aftergadolinium administration, diffuse T2/FLAIR signal, and involvement of morethan 50% of the pons.
Confirmation of anaplastic glioma (i.e., oligodendroglioma, astrocytoma,oligoastrocytoma) or GBM histology if there is less than 50% involvement of thepons.
Screening evaluation requires a MRI performed within 14 days prior to the start ofANP therapy. Study subjects must be on a fixed dose of steroids for at least fivedays prior to the screening MRI. If the steroid dose is changed between the date ofimaging and the start of treatment, a new baseline MRI is required. All MRIs must beperformed at an accredited radiology center. All MRIs should include at a minimum:T1-weighted images pre/post gadolinium administration, fluid attenuated inversionrecovery (FLAIR), and T-2 weighted images.
Subjects 3-21 years of age must have a clinical history of disease of less than 6months 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 ofage do not need to meet these criteria.
Subjects must be ≥ 3 years of age. RT is not recommended for subjects less than 3years 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 developinghuman fetus are unknown. For this reason, women of child-bearing potential who agreeto use adequate contraception (hormonal or barrier method of birth control;abstinence) prior to protocol study entry and for the duration of the protocol studyare eligible. Should a woman become pregnant or suspect she is pregnant whileparticipating in this protocol study, she will inform her treating physicianimmediately.
Subjects, parents, and/or guardians who are able to understand a written informedconsent document, and are willing to sign it, are eligible.

Exclusion

Exclusion Criteria:

No type of prior therapy, including other investigational agents, is allowable. Aprior diagnostic biopsy or surgical shunt for hydrocephalus is permitted.
Subjects with disseminated disease, multicentric tumors, leptomeningeal disease, orthe history of retrotumoral bleeding are not eligible. The screening / baseline MRIincludes 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 arenot eligible. - Subjects with a current diagnosis or family history ofneurofibromatosis are not eligible.
Subjects with an uncontrolled intercurrent illness including, but not limited to,ongoing or active infection, uncontrolled hypertension despite maximal medicalmanagement (three supine blood pressure measurements ≥ 150/99 taken at least onehour apart) or psychiatric illness/social situations that would limit compliancewith protocol study requirements are not eligible.
Subjects with a history of New York Heart Association Class II congestive heartfailure are not eligible.
Pregnant women are not eligible because the teratogenic and abortifacient effects ofANP therapy in humans are unknown. Because there is an unknown but potential riskfor adverse events in nursing infants secondary to the mother receiving ANP therapy,breastfeeding is discontinued if the mother receives ANP therapy.

Study Design

Radiation

October 01, 2025

June 30, 2026

Study 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.