Antineoplaston Therapy in Treating Children With Primary Malignant Brain Tumors

• Sponsor: Burzynski Research Institute (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00003476
• Collaborator: (none)
• Enrollment: 8
• Location: 1
• Arm: 1
• Duration (Months): 190
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Current therapies for children with primary malignant brain tumors provide limited benefit to the patient. The anti-cancer properties of Antineoplaston therapy suggest that it may prove beneficial in the treatment of children with primary malignant brain tumors.

PURPOSE: This study is being performed to determine the effects (good and bad) that Antineoplaston therapy has on children with primary malignant brain tumors.

Condition or Disease	Intervention/Treatment	Phase
Childhood Brain Tumor	Drug: Antineoplaston therapy (Atengenal + Astugenal)	Phase 2

Detailed Description

OBJECTIVES:

• To determine the efficacy of Antineoplaston therapy in children with primary malignant brain tumors 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 primary malignant brain tumors.

OVERVIEW: This is a single arm, open-label study in which children with primary malignant brain tumors 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 to this study

Study Design

• Study Type: Interventional
• Actual Enrollment: 8 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 Primary Malignant Brain Tumors
• Study Start Date: Mar 1, 1996
• Actual Primary Completion Date: Jan 1, 2012
• Actual Study Completion Date: Jan 1, 2012

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 primary malignant brain tumor 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; Stable Disease (SD), <50% decrease and <25% increase in the sum of the products of of the greatest perpendicular diameters of all measurable enhancing lesions, sustained for at least eight weeks; Progressive Disease (PD), >=25% increase in the sum of the products of of the greatest perpendicular diameters of all measurable enhancing lesions.

Secondary Outcome Measures

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

   Six months and Twelve months overall survival

Eligibility Criteria

Criteria

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

DISEASE CHARACTERISTICS:

• Histologically confirmed incurable primary malignant brain tumor that has progressed, recurred, or persisted after initial therapy (must have failed standard therapy).

• Evidence of residual tumor by MRI performed within two weeks prior to study entry

PATIENT CHARACTERISTICS:

Age:

• 6 months to 17 years

Performance status:

• Karnofsky 60-100%

Life expectancy:

• At least 2 months

Hematopoietic:

• WBC at least 1,500/mm^3

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

Hepatic:

• No hepatic failure

• Bilirubin no greater than 2.5 mg/dL

• SGOT/SGPT no greater than 5 times upper limit of normal

Renal:

• Creatinine no greater than 2.5 mg/dL

Cardiovascular:

• No severe heart disease

• No uncontrolled hypertension

Pulmonary:

• No severe lung disease

Other:

• Not pregnant or nursing

• Fertile patients must use effective contraception during and for 4 weeks after study participation

• No serious active infections or fever

• No other serious concurrent disease

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 4 weeks since prior immunotherapy and recovered

• No concurrent immunomodulating agents

Chemotherapy:

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered

• No concurrent antineoplastic agents

Endocrine therapy:

• Recovered from prior endocrine therapy

• Concurrent corticosteroids for cerebral edema allowed

Radiotherapy:

• At least 8 weeks since prior radiotherapy (unless clear radiological evidence of progression) and recovered

Surgery:

• At least 4 weeks since prior surgery (unless clear radiological evidence of progression) and recovered

Other:

• No prior antineoplaston therapy

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

• Burzynski SR, Janicki TJ, Burzynski GS, Marszalek A, Brookman, S. A phase II study of Antineoplastons A10 and AS2-1 in children with recurrent, refractory or progressive primary brain tumors - Final Report (Protocol BT-22). Journal of Cancer Therapy, 5:977-988, 2014.

• Responsible Party: Burzynski Research Institute
• ClinicalTrials.gov Identifier: NCT00003476
• Other Study ID Numbers: CDR0000066513; BC-BT-22
• First Posted: Jan 27, 2003
• Last Update Posted: Aug 24, 2017
• Last Verified: Jul 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Burzynski Research Institute: childhood anaplastic astrocytoma; recurrent childhood anaplastic astrocytoma; childhood glioblastoma multiforme; recurrent childhood glioblastoma multiforme; childhood brainstem glioma; recurrent childhood brainstem glioma; childhood primitive neuroectodermal tumor; recurrent childhood primitive neuroectodermal tumor
• Additional relevant MeSH terms: Brain Neoplasms

Study Results

Participant Flow

Recruitment Details	Eight patients were recruited between March 1966 and November 2011. 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 primary malignant brain tumor will receive Antineoplaston therapy (Atengenal + Astugenal).
Period Title: Overall Study
STARTED	8
COMPLETED	7
NOT COMPLETED	1

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 primary malignant brain tumor will receive Antineoplaston therapy (Atengenal + Astugenal).
Overall Participants	8
Age (Years) [Median (Full Range) ]
Median (Full Range) [Years]	9.1
Sex: Female, Male (Count of Participants)
Female	6 75%
Male	2 25%

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; Stable Disease (SD), <50% decrease and <25% increase in the sum of the products of of the greatest perpendicular diameters of all measurable enhancing lesions, sustained for at least eight weeks; Progressive Disease (PD), >=25% increase in the sum of the products of of the greatest perpendicular diameters of all measurable enhancing lesions.
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 primary malignant brain tumor will receive Antineoplaston therapy (Atengenal + Astugenal).
Measure Participants	7
Partial Response	1 12.5%
Stable Disease	1 12.5%
Progressive Disease	5 62.5%

2. Secondary Outcome

Title	Percentage of Participants Who Survived
Description	Six months and Twelve months overall survival
Time Frame	6 months, 12 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 primary malignant brain tumor will receive Antineoplaston therapy (Atengenal + Astugenal).
Measure Participants	8
6 months overall survival	50.0 625%
12 months overall survival	0 0%

Adverse Events

Time Frame	15 years, 10 months
Adverse Event Reporting Description	Eight patients were recruited between March 1996 and November 2011. 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 primary malignant brain tumor 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	2/8 (25%)
Gastrointestinal disorders
Vomiting	1/8 (12.5%)
General disorders
Central venous catheter: Thrombosis/embolism	1/8 (12.5%)
Fever	1/8 (12.5%)
Infections and infestations
Infection (documented clinically): Lung (pneumonia)	1/8 (12.5%)
Nervous system disorders
Hydrocephalus	1/8 (12.5%)
Seizure	1/8 (12.5%)
Respiratory, thoracic and mediastinal disorders
Aspiration	1/8 (12.5%)
Other (Not Including Serious) Adverse Events
	Antineoplaston Therapy
	Affected / at Risk (%)	# Events
Total	8/8 (100%)
Blood and lymphatic system disorders
Hemoglobin	2/8 (25%)
Leukocytes (total WBC)	1/8 (12.5%)
Lymphopenia	3/8 (37.5%)
Neutrophils/granulocytes (ANC/AGC)	1/8 (12.5%)
Ear and labyrinth disorders
Hearing (without monitoring program)	1/8 (12.5%)
Endocrine disorders
Cushingoid appearance	2/8 (25%)
Eye disorders
Diplopia	1/8 (12.5%)
Vision-blurred vision	1/8 (12.5%)
Gastrointestinal disorders
Anorexia	1/8 (12.5%)
Dry mouth/salivary gland (xerostomia)	2/8 (25%)
Dysphagia (difficulty swallowing)	1/8 (12.5%)
Nausea	3/8 (37.5%)
Vomiting	5/8 (62.5%)
General disorders
Central venous catheter: Thrombosis/embolism	1/8 (12.5%)
Fatigue (asthenia, lethargy, malaise)	3/8 (37.5%)
Fever	4/8 (50%)
Rigors/chills	1/8 (12.5%)
Weight gain	2/8 (25%)
Infections and infestations
Infection (documented clinically): Conjunctiva	1/8 (12.5%)
Infection (documented clinically): Lung (pneumonia)	1/8 (12.5%)
Infection (documented clinically): Mucosa	1/8 (12.5%)
Infection (documented clinically): Sinus	1/8 (12.5%)
Infection (documented clinically): Upper airway NOS	1/8 (12.5%)
Sinus	1/8 (12.5%)
Hypercholesteremia	1/8 (12.5%)
Investigations
Alkaline phosphatase	2/8 (25%)
Bicarbonate, serum-low	1/8 (12.5%)
GGT (gamma-Glutamyl transpeptidase)	1/8 (12.5%)
Hyperchloremia	1/8 (12.5%)
Hyperglycemia	1/8 (12.5%)
Hypernatremia	1/8 (12.5%)
Hypocalcemia	1/8 (12.5%)
Hypoglycemia	1/8 (12.5%)
Hypokalemia	8/8 (100%)
Hypomagnesemia	2/8 (25%)
Metabolic/Laboratory - Other	1/8 (12.5%)
Uric acid, serum-high (hyperuricemia)	1/8 (12.5%)
Nervous system disorders
Apnea	1/8 (12.5%)
Ataxia (incoordination)	1/8 (12.5%)
Hydrocephalus	1/8 (12.5%)
Neuropathy - motor	1/8 (12.5%)
Neuropathy: CN III Pupil, upper eyelid, extra ocular movements	1/8 (12.5%)
Neuropathy: cranial: CN V Motor-jaw muscles; Sensory-facial	1/8 (12.5%)
Neuropathy: cranial: CN VII Motor-face; Sensory-taste	1/8 (12.5%)
Neuropathy: cranial: CN VIII Hearing and balance	1/8 (12.5%)
Neuropathy: motor	1/8 (12.5%)
Seizure	1/8 (12.5%)
Somnolence/depressed level of consciousness	6/8 (75%)
Speech impairment	1/8 (12.5%)
Pain: Head/headache	3/8 (37.5%)
Respiratory, thoracic and mediastinal disorders
Aspiration	1/8 (12.5%)
Dyspnea (shortness of breath)	2/8 (25%)
Nasal cavity/paranasal sinus reactions	1/8 (12.5%)
Skin and subcutaneous tissue disorders
Flushing	1/8 (12.5%)
Rash/desquamation	1/8 (12.5%)

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.