AA: Antineoplaston Therapy in Treating Patients With Anaplastic Astrocytoma

• Sponsor: Burzynski Research Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT00003470
• Collaborator: (none)
• Enrollment: 27
• Location: 1
• Arm: 1
• Duration (Months): 165
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

RATIONALE: Current therapies for adults with anaplastic astrocytomas that have not responded to standard therapy provide very limited benefit to the patient. The anti-cancer properties of Antineoplaston therapy suggest that it may prove beneficial in the treatment of adults with anaplastic astrocytomas that have not responded to standard therapy.

PURPOSE: This study is being performed to determine the effects (good and bad) that Antineoplaston therapy has on adults with anaplastic astrocytomas that have not responded to standard therapy.

Condition or Disease	Intervention/Treatment	Phase
Anaplastic Astrocytoma	Drug: Antineoplaston therapy (Atengenal + Astugenal)	Phase 2

Detailed Description

OBJECTIVES:

• To determine the efficacy of Antineoplaston therapy in patients with anaplastic astrocytomas that have not responded to standard therapy, 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 patients with a anaplastic astrocytoma

OVERVIEW: This is a single arm, open-label study in which adults withanaplastic astrocytomas that have not responded to standard therapy 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: 27 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 Adult Patients With Anaplastic Astrocytoma
• Study Start Date: Mar 1, 1996
• Actual Primary Completion Date: Dec 1, 2008
• Actual Study Completion Date: Dec 1, 2009

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); Adults with an anaplastic astrocytoma that has not responded to standard therapy will receive Antineoplaston therapy (Atengenal + Astugenal). The daily doses of A10 and AS2-1 are divided into six infusions, which are given at 4-hourly intervals. Each infusion starts with infusion of A10 and is immediately followed by infusion of AS2-1.; 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, 24 months, 36 months, 48 months, 60 months]

   6 months, 12 months, 24 months, 36 months, 48 months, 60 months overall survival

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 99 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed incurable adult anaplastic astrocytoma

• Evidence of progressive or recurrent tumor by MRI scan performed within 2 weeks prior to study entry

• Must have received and failed standard therapy

• Tumor must be at least 5 mm

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 60-100%

Life expectancy:

• At least 2 months

Hematopoietic:

• WBC at least 2000/mm^3

• Platelet count at least 50,000/mm^3

Hepatic:

• Bilirubin no greater than 2.5 mg/dL

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

• No hepatic failure

Renal:

• Creatinine no greater than 2.5 mg/dL

• No history of renal conditions that contraindicate high dosages of sodium

Cardiovascular:

• No uncontrolled hypertension

• No history of congestive heart failure

• No history of other cardiovascular conditions that contraindicate high dosages of sodium

Pulmonary:

• No serious lung disease such as severe chronic obstructive pulmonary disease

Other:

• Not pregnant or nursing

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

• No active infection

• 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:

• Concurrent corticosteroids allowed

Radiotherapy:

• At least 8 weeks since prior radiotherapy and recovered

Surgery:

• Fully recovered from any prior surgery

Other:

• Prior cytodifferentiating agent allowed

• 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. A phase II study of Antineoplastons A10 and AS2-1 injections in adult patients with recurrent anaplastic astrocytoma - Final report (Protocol BT-15). Cancer and Clinical Oncology 4(2): 13-23, 2015. DOI: http://dx.doi.org/10.5539/cco.v4n2p13

• Responsible Party: Burzynski Research Institute
• ClinicalTrials.gov Identifier: NCT00003470
• Other Study ID Numbers: CDR0000066507; BC-BT-15
• First Posted: Jan 27, 2003
• Last Update Posted: Aug 24, 2017
• Last Verified: Dec 1, 2016

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Burzynski Research Institute: persistent anaplastic astrocytoma; recurrent anaplastic astrocytoma; adult anaplastic astrocytoma
• Additional relevant MeSH terms: Astrocytoma

Study Results

Participant Flow

Recruitment Details	Twenty-seven patients were recruited between March 1996 and November 2007. 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): Adults with an anaplastic astrocytoma that has not responded to standard therapy will receive Antineoplaston therapy (Atengenal + Astugenal).
Period Title: Overall Study
STARTED	27
COMPLETED	21
NOT COMPLETED	6

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): Adults with an anaplastic astrocytoma that has not responded to standard therapy will receive Antineoplaston therapy (Atengenal + Astugenal). The daily doses of A10 and AS2-1 are divided into six infusions, which are given at 4-hourly intervals. Each infusion starts with infusion of A10 and is immediately followed by infusion of AS2-1.
Overall Participants	27
Age (Years) [Median (Full Range) ]
Median (Full Range) [Years]	41.5
Sex: Female, Male (Count of Participants)
Female	7 25.9%
Male	20 74.1%

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): Adults with an anaplastic astrocytoma that has not responded to standard therapy will receive Antineoplaston therapy (Atengenal + Astugenal). The daily doses of A10 and AS2-1 are divided into six infusions, which are given at 4-hourly intervals. Each infusion starts with infusion of A10 and is immediately followed by infusion of AS2-1.
Measure Participants	21
Complete Response	2 7.4%
Partial Response	3 11.1%
Stable Disease	6 22.2%
Progressive Disease	10 37%

2. Secondary Outcome

Title	Percentage of Participants Who Survived
Description	6 months, 12 months, 24 months, 36 months, 48 months, 60 months overall survival
Time Frame	6 months, 12 months, 24 months, 36 months, 48 months, 60 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): Adults with an anaplastic astrocytoma that has not responded to standard therapy will receive Antineoplaston therapy (Atengenal + Astugenal). The daily doses of A10 and AS2-1 are divided into six infusions, which are given at 4-hourly intervals. Each infusion starts with infusion of A10 and is immediately followed by infusion of AS2-1.
Measure Participants	27
6 months overall survival	63.0 233.3%
12 months overall survival	40.7 150.7%
24 months overall survival	29.6 109.6%
36 months overall survival	22.2 82.2%
48 months overall survival	14.8 54.8%
60 months overall survival	11.1 41.1%

Adverse Events

Time Frame	12 years, nine months
Adverse Event Reporting Description	Adverse event data was collected through regular patient assessment and regular laboratory testing
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): Adults with an anaplastic astrocytoma that has not responded to standard therapy 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	12/27 (44.4%)
Gastrointestinal disorders
Vomiting	1/27 (3.7%)
General disorders
Fatigue (asthenia, lethargy, malaise)	2/27 (7.4%)
Edema/Fluid retention	1/27 (3.7%)
Infections and infestations
Central venous catheter infection	3/27 (11.1%)
Infection (documented clinically): Bladder (urinary)	1/27 (3.7%)
Infection (documented clinically): Lung (pneumonia)	2/27 (7.4%)
Infection (documented clinically): Skin (cellulitis)	1/27 (3.7%)
Infection with normal ANC: Brain + Spinal cord (encephalomyelitis)	1/27 (3.7%)
Lung (pneumonia)	1/27 (3.7%)
Investigations
Hypernatremia	1/27 (3.7%)
Hypokalemia	1/27 (3.7%)
SGPT	1/27 (3.7%)
Nervous system disorders
Ataxia (incoordination)	1/27 (3.7%)
Confusion	2/27 (7.4%)
Mood alteration: Agitation	1/27 (3.7%)
Seizure	3/27 (11.1%)
Somnolence/depressed level of consciousness	3/27 (11.1%)
Tremor	1/27 (3.7%)
Respiratory, thoracic and mediastinal disorders
Pulmonary/Upper Respiratory - Other (Pneumonia)	1/27 (3.7%)
Vascular disorders
Thrombosis/thrombus/embolism	1/27 (3.7%)
Other (Not Including Serious) Adverse Events
	Antineoplaston Therapy
	Affected / at Risk (%)	# Events
Total	27/27 (100%)
Blood and lymphatic system disorders
Hemoglobin	6/27 (22.2%)
Leukocytes (total WBC)	3/27 (11.1%)
Lymphopenia	4/27 (14.8%)
Platelets	4/27 (14.8%)
Cardiac disorders
Hypertension	2/27 (7.4%)
Ear and labyrinth disorders
Tinnitus	2/27 (7.4%)
Endocrine disorders
Hot flashes/flushes	2/27 (7.4%)
Eye disorders
Vision-blurred vision	2/27 (7.4%)
Gastrointestinal disorders
Diarrhea	5/27 (18.5%)
Dry mouth/salivary gland (xerostomia)	5/27 (18.5%)
Heartburn/dyspepsia	3/27 (11.1%)
Nausea	12/27 (44.4%)
Taste alteration (dysgeusia)	2/27 (7.4%)
Vomiting	7/27 (25.9%)
General disorders
Non-functional central venous catheter	9/27 (33.3%)
Central venous catheter - Other	2/27 (7.4%)
Pain: Central venous catheter	4/27 (14.8%)
Central venous catheter thrombosis/embolism	2/27 (7.4%)
Fatigue (asthenia, lethargy, malaise)	20/27 (74.1%)
Fever	4/27 (14.8%)
Insomnia	3/27 (11.1%)
Rigors/chills	3/27 (11.1%)
Weight gain	3/27 (11.1%)
Edema/Fluid retention	14/27 (51.9%)
Immune system disorders
Allergic reaction/hypersensitivity (including drug fever)	4/27 (14.8%)
Allergic rhinitis (including sneezing, nasal stuffiness,	2/27 (7.4%)
Infections and infestations
Central venous catheter infection	7/27 (25.9%)
Infection (documented clinically): Bladder (urinary)	3/27 (11.1%)
Infection (documented clinically): Lung (pneumonia)	2/27 (7.4%)
Infection (documented clinically): Skin (cellulitis)	2/27 (7.4%)
Infection (documented clinically): Upper airway NOS	3/27 (11.1%)
Opportunistic infection	2/27 (7.4%)
Investigations
Albumin, serum-low (hypoalbuminemia)	2/27 (7.4%)
Alkaline phosphatase	3/27 (11.1%)
Hypercholesteremia	2/27 (7.4%)
Hyperglycemia	10/27 (37%)
Hyperkalemia	2/27 (7.4%)
Hypernatremia	21/27 (77.8%)
Hypocalcemia	7/27 (25.9%)
Hypoglycemia	6/27 (22.2%)
Hypokalemia	22/27 (81.5%)
Hypomagnesemia	5/27 (18.5%)
Hyponatremia	3/27 (11.1%)
Hypophosphatemia	4/27 (14.8%)
Metabolic/Laboratory - Other	2/27 (7.4%)
Proteinuria	7/27 (25.9%)
SGOT	6/27 (22.2%)
SGPT	3/27 (11.1%)
Musculoskeletal and connective tissue disorders
Pain: Back	3/27 (11.1%)
Pain: Extremity-limb	3/27 (11.1%)
Pain: Joint	3/27 (11.1%)
Nervous system disorders
Ataxia (incoordination)	4/27 (14.8%)
Confusion	10/27 (37%)
Dizziness	9/27 (33.3%)
Mood alteration: Agitation	2/27 (7.4%)
Neuropathy: motor	2/27 (7.4%)
Psychosis (hallucinations/delusions)	2/27 (7.4%)
Seizure	7/27 (25.9%)
Somnolence/depressed level of consciousness	17/27 (63%)
Speech impairment	7/27 (25.9%)
Tremor	4/27 (14.8%)
Pain: Head/headache	9/27 (33.3%)
Renal and urinary disorders
Hemorrhage, GU: Urinary NOS	3/27 (11.1%)
Urinary frequency/urgency	5/27 (18.5%)
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)	4/27 (14.8%)
Skin and subcutaneous tissue disorders
Dermatology/Skin - Other	2/27 (7.4%)

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.