Antineoplaston Therapy in Treating Children With Recurrent or Refractory High-Grade Glioma

• Sponsor: Burzynski Research Institute (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00003535
• Collaborator: (none)
• Enrollment: 9
• Location: 1
• Arm: 1
• Duration (Months): 45
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

RATIONALE: Current therapies for children with recurrent/progressive high grade gliomas provide very limited benefit to the patient. The anti-cancer properties of Antineoplaston therapy suggest that it may prove beneficial in the treatment of children with recurrent/progressive high grade gliomas.

PURPOSE: This study is being performed to determine the effects (good and bad) that Antineoplaston therapy has on children (> 6 months of age) with recurrent/progressive high grade gliomas.

Condition or Disease	Intervention/Treatment	Phase
High Grade Glioma	Drug: Antineoplaston therapy (Atengenal + Astugenal)	Phase 2

Detailed Description

OBJECTIVES:

• To determine the efficacy of Antineoplaston therapy in children with recurrent/progressive high grade gliomas, as measured by an objective response to therapy (complete response, partial response or stable disease).

• To determine the safety and tolerance of Antineoplaston therapy in children with recurrent/progressive high grade gliomas.

OVERVIEW: This is a single arm, open-label study in which children with recurrent/progressive high grade gliomas receive gradually escalating doses of intravenous Antineoplaston therapy (Atengenal + Astugenal) until the maximum tolerated dose is reached. Treatment continues for at least 12 months in the absence of disease progression or unacceptable toxicity. After 12 months, patients with a complete or partial response or with stable disease may continue treatment.

To determine objective response, tumor size is measured utilizing MRI scans, which are performed every 8 weeks for the first two years, every 3 months for the third and fourth years, every 6 months for the 5th and sixth years, and annually thereafter.

PROJECTED ACCRUAL: A total of 20-40 patients will be accrued for this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 9 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Antineoplastons A10 and AS2-1 in Children With High Grade Glioma
• Study Start Date: Apr 1, 1994
• Actual Primary Completion Date: Jan 1, 1998
• Actual Study Completion Date: Jan 1, 1998

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Antineoplaston therapy Antineoplaston therapy (Atengenal + Astugenal) by IV infusion every four hours for at least 12 months. Study subjects receive increasing dosages of Atengenal and Astugenal until the maximum tolerated dose is reached.	Drug: Antineoplaston therapy (Atengenal + Astugenal); Children with a recurrent/progressive high grade glioma will receive Antineoplaston therapy (Atengenal + Astugenal).; Other Names: A10 (Atengenal); AS2-1 (Astugenal)

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Objective Response [12 months]

   Objective response rate per Response Assessment in Neuro-Oncology (RANO) for target lesions and assessed by MRI: Complete Response (CR), disappearance of all disease sustained for at least four weeks; Partial Response (PR), >=50% decrease in the sum of the products of of the greatest perpendicular diameters of all measurable enhancing lesions, sustained for at least four weeks.

Secondary Outcome Measures

1. Percentage of Participants Who Survived [6 months, 12 months, 24 months]

   6 months, 12 months, 24 months overall survival

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Months to 18 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically confirmed high-grade glioma (glioblastoma multiforme or anaplastic astrocytoma) that is recurrent or progressive or with residual tumor after standard therapy, including radiotherapy

• Measurable tumor by MRI scan performed within two weeks prior to study entry

• Male or female patients

• Children 6 months to 17 years

• Performance status: Karnofsky 60-100%

• Life expectancy of at least 2 months

• WBC greater than 1,500/mm^3

• Platelet count greater than 50,000/mm^3

• No evidence of hepatic or renal insufficiency and a total bilirubin and serum creatinine no greater than 2.5 mg/dL and SGOT/SGPT no greater than 5 times upper limit of normal

• Must have recovered from adverse effect of previous therapy

• At least 8 weeks elapsed since last dose of radiation

• At least 4 weeks elapsed since last dose of chemotherapy (6 weeks for nitrosoureas)

• Corticosteroids permitted using the smallest dose that is compatible with preservation of optimal neurologic function

• Acceptable methods of birth control (in females of child-bearing potential or in sexually active males)during and up to four weeks following completion of study

Exclusion Criteria:

• Prior A10 and AS2-1 treatment

• Severe heart disease

• Uncontrolled hypertension

• Lung disease

• Hepatic failure

• Serious active infections, fever or other serious concurrent disease that would interfere with the evaluation of the treatment drug.

• Pregnant or nursing

• Serious concurrent disease

• Concurrent antineoplastic or immunomodulatory agents

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Burzynski Clinic	Houston	Texas	United States	77055-6330

Sponsors and Collaborators

• Burzynski Research Institute

Investigators

• Principal Investigator: Stanislaw R. Burzynski, MD, PhD, Burzynski Research Institute

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Burzynski Research Institute
• Burzynski Clinic

Publications

None provided.

• Responsible Party: Burzynski Research Institute
• ClinicalTrials.gov Identifier: NCT00003535
• Other Study ID Numbers: CDR0000066582; BC-BT-06
• First Posted: Jan 27, 2003
• Last Update Posted: Mar 21, 2018
• Last Verified: Mar 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Burzynski Research Institute: childhood anaplastic astrocytoma; childhood glioblastoma multiforme
• Additional relevant MeSH terms: Glioma

Study Results

Participant Flow

Recruitment Details	Nine patients were recruited between April 1994 and August 1997. All study subjects were seen at the Burzynski Clinic in Houston TX

Arm/Group Title	Antineoplaston Therapy
Arm/Group Description	Antineoplaston therapy (Atengenal + Astugenal) by IV infusion every four hours for at least 12 months. Study subjects receive increasing dosages of Atengenal and Astugenal until the maximum tolerated dose is reached. Antineoplaston therapy (Atengenal + Astugenal): Children with a recurrent/progressive high grade glioma will receive Antineoplaston therapy (Atengenal + Astugenal).
Period Title: Overall Study
STARTED	9
COMPLETED	4
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	Antineoplaston Therapy
Arm/Group Description	Antineoplaston therapy (Atengenal + Astugenal) by IV infusion every four hours for at least 12 months. Study subjects receive increasing dosages of Atengenal and Astugenal until the maximum tolerated dose is reached. Antineoplaston therapy (Atengenal + Astugenal): Children with a recurrent/progressive high grade glioma will receive Antineoplaston therapy (Atengenal + Astugenal).
Overall Participants	9
Age (Years) [Median (Full Range) ]
Median (Full Range) [Years]	9.7
Sex: Female, Male (Count of Participants)
Female	1 11.1%
Male	8 88.9%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Objective Response
Description	Objective response rate per Response Assessment in Neuro-Oncology (RANO) for target lesions and assessed by MRI: Complete Response (CR), disappearance of all disease sustained for at least four weeks; Partial Response (PR), >=50% decrease in the sum of the products of of the greatest perpendicular diameters of all measurable enhancing lesions, sustained for at least four weeks.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Antineoplaston Therapy
Arm/Group Description	Antineoplaston therapy (Atengenal + Astugenal) by IV infusion every four hours for at least 12 months. Study subjects receive increasing dosages of Atengenal and Astugenal until the maximum tolerated dose is reached. Antineoplaston therapy (Atengenal + Astugenal): Children with a recurrent/progressive high grade glioma will receive Antineoplaston therapy (Atengenal + Astugenal).
Measure Participants	4
Complete Response	1 11.1%
Partial Response	1 11.1%
Progressive Disease	2 22.2%

2. Secondary Outcome

Title	Percentage of Participants Who Survived
Description	6 months, 12 months, 24 months overall survival
Time Frame	6 months, 12 months, 24 months

Outcome Measure Data

Analysis Population Description

All study subjects receiving any Antineoplaston therapy

Arm/Group Title	Antineoplaston Therapy
Arm/Group Description	Antineoplaston therapy (Atengenal + Astugenal) by IV infusion every four hours for at least 12 months. Study subjects receive increasing dosages of Atengenal and Astugenal until the maximum tolerated dose is reached. Antineoplaston therapy (Atengenal + Astugenal): Children with a recurrent/progressive high grade glioma will receive Antineoplaston therapy (Atengenal + Astugenal).
Measure Participants	9
6 months overall survival	22.2 246.7%
12 months overall survival	11.1 123.3%
24 months overall survival	0.0 0%

Adverse Events

Time Frame	3 years, 9 months
Adverse Event Reporting Description	Thirteen patients were recruited between April 1994 and August 1997. All study subjects were seen at the Burzynski Clinic in Houston TX
Arm/Group Title	Antineoplaston Therapy
Arm/Group Description	Antineoplaston therapy (Atengenal + Astugenal) by IV infusion every four hours for at least 12 months. Study subjects receive increasing dosages of Atengenal and Astugenal until the maximum tolerated dose is reached. Antineoplaston therapy (Atengenal + Astugenal): Children with a recurrent/progressive high grade glioma will receive Antineoplaston therapy (Atengenal + Astugenal).
All Cause Mortality
	Antineoplaston Therapy
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Antineoplaston Therapy
	Affected / at Risk (%)	# Events
Total	7/9 (77.8%)
Blood and lymphatic system disorders
Platelets	1/9 (11.1%)
Gastrointestinal disorders
Dehydration	1/9 (11.1%)
Vomiting	1/9 (11.1%)
General disorders
Central Venous Catheter: Infection	1/9 (11.1%)
Infections and infestations
Infection: Other	1/9 (11.1%)
Infection (documented clinically): Lung (pneumonia)	1/9 (11.1%)
Investigations
Hypernatremia	1/9 (11.1%)
Nervous system disorders
Seizure	1/9 (11.1%)
Somnolence/depressed level of consciousness	1/9 (11.1%)
Pain: Head/headache	1/9 (11.1%)
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)	1/9 (11.1%)
Pleural effusion (non-malignant)	1/9 (11.1%)
Other (Not Including Serious) Adverse Events
	Antineoplaston Therapy
	Affected / at Risk (%)	# Events
Total	9/9 (100%)
Blood and lymphatic system disorders
Hemoglobin	1/9 (11.1%)
Leukocytes (total WBC)	1/9 (11.1%)
Lymphopenia	1/9 (11.1%)
Neutrophils/granulocytes (ANC/AGC)	2/9 (22.2%)
Platelets	3/9 (33.3%)
Cardiac disorders
Supraventricular and nodal arrhythmia: Sinus tachycardia	1/9 (11.1%)
Hypertension	1/9 (11.1%)
Gastrointestinal disorders
Dehydration	1/9 (11.1%)
Diarrhea	2/9 (22.2%)
Nausea	2/9 (22.2%)
Vomiting	4/9 (44.4%)
General disorders
Fatigue (asthenia, lethargy, malaise)	3/9 (33.3%)
Fever	1/9 (11.1%)
Edema/Fluid retention	1/9 (11.1%)
Immune system disorders
Allergic reaction/hypersensitivity (including drug fever)	1/9 (11.1%)
Infections and infestations
Central Venous Catheter: Infection	1/9 (11.1%)
Infection: Other	1/9 (11.1%)
Infection (documented clinically): Lung (pneumonia)	2/9 (22.2%)
Infection (documented clinically): Mucosa	2/9 (22.2%)
Infection (documented clinically): Upper airway NOS	1/9 (11.1%)
Investigations
Hypercholesteremia	1/9 (11.1%)
Hyperglycemia	2/9 (22.2%)
Hypokalemia	8/9 (88.9%)
Hypomagnesemia	1/9 (11.1%)
Hypophosphatemia	1/9 (11.1%)
Proteinuria	1/9 (11.1%)
Hypernatremia	5/9 (55.6%)
Nervous system disorders
Confusion	2/9 (22.2%)
Seizure	1/9 (11.1%)
Somnolence/depressed level of consciousness	4/9 (44.4%)
Speech impairment	2/9 (22.2%)
Pain: Head/headache	1/9 (11.1%)
Renal and urinary disorders
Hemorrhage, GU: Bladder	1/9 (11.1%)
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)	3/9 (33.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.