Phase 3 Study of ANP Therapy vs. TMZ for Optic Pathway Glioma

NCT01260103 | Withdrawn Phase 3

• 1 other identifier: BRI-BT-54
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Primary Objectives To compare progression free survival (PFS), the time from randomization to progressive disease,in children with optic pathway glioma (OPG) age ≥ 6 months to \< 18 years, who receive combination antineoplaston therapy (ANP therapy) vs. temozolomide (TMZ); study subjects will have 1) received prior treatment with carboplatin or cisplatin, which was terminated secondary to toxicity or progression of OPG, or 2) developed recurrence of OPG after completion of carboplatin or cisplatin therapy. PFS data will be censored on the date of the last tumor assessment documenting absence of progression for study subjects:

• Who are alive, on study and are progression-free at the time of the analysis;
• Who discontinue, receive no subsequent therapy and are progression-free at the time of the analysis;
• Who are given/change therapy other than the study treatment prior to observing progression;
• Who discontinued (due to personal preference or toxicity) with a change in therapy, withdrew, or was lost to follow-up;
• For whom documentation of disease progression or death occurs after ≥ 2 consecutive missed tumor assessments.
• To describe the toxicity profile for ANP therapy vs. TMZ. Secondary Objectives:
• To compare overall survival (OS) for subjects treated with ANP therapy vs. TMZ;
• To compare disease stabilization rates for subjects treated with ANP therapy vs. TMZ;
• To compare complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) rates for subjects treated with ANP therapy vs. TMZ.

Conditions

Optic Nerve Glioma

Keywords

Optic pathway glioma, recurrent; Optic pathway glioma, progressive; Temozolomide; Temodar; TMZ; Antineoplastons; ANP therapy; Atengenal (A10); Astugenal (AS2-1)

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS)

  PFS will be summarized using tables produced by SAS Proc Lifetest (version 9.2 or later). Standard errors will be computed using the Greenwood formula and 95% confidence intervals produced using the loglog transform. The Log Rank test will be used to compare the two treatment groups with respect to PFS. All tests will be at the two-sided 0.050 significance level.

  5 years

Secondary Outcomes (1)

• Safety Analysis

  5 years

Study Arms (2)

Temozolomide (TMZ)

ACTIVE COMPARATOR

Study subjects receive TMZ for 13 cycles

Drug: Temozolomide

ANP Therapy

EXPERIMENTAL

Escalating doses of ANP therapy are given daily for 52 weeks.

Drug: ANP Therapy

Interventions

Temozolomide DRUG

Study subjects in a fasting state receive TMZ orally once a day for five consecutive days (days 1 through 5) at a starting dose of 200 mg/m2/day. Treatment cycles are repeated every 28 days following the first daily dose of TMZ from the previous cycle. In the absence of PD or unacceptable toxicity, subjects continue to receive TMZ for a maximum of 13 cycles.

Also known as: Temodar, TMZ

Temozolomide (TMZ)

ANP Therapy DRUG

Escalating doses of ANP therapy are administered for 52 weeks. If the study subject has an OR or maintains SD, ANP therapy is continued.

Also known as: Antineoplastons, Astengenal (A10), Astugenal (AS2-1)

ANP Therapy

Eligibility Criteria

• Age: 6 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Children age ≥ 6 months \< 18 years are eligible if they have 1) received prior treatment with carboplatin or cisplatin, which was terminated secondary to toxicity or progression of OPG or 2) developed recurrence of OPG after completion of carboplatin or cisplatin therapy.
• Children with or without prior RT are eligible.
• Histological confirmation of OPG is required unless the risks of obtaining a diagnostic biopsy are prohibitive.
• Evidence of OPG (≥ 5 mm), as diagnosed by MRI of the brain, with and without gadolinium contrast, within four weeks of protocol study entry is required. The MRI is interpreted by two independent neuroradiologists. If there is disagreement, a third independent neuroradiologist will adjudicate. Baseline MR spectroscopy (MRS) and positron emission tomography (PET) scan are also performed.
• Children who are receiving corticosteroids and, for at least one week prior to entry into the protocol study have been on the lowest dose of corticosteroids that preserves optimal neurologic function, are eligible.
• Children with a life expectancy of \> 6 months are eligible.
• Children ≤ 14 years of age with a Lansky performance status of \> 60 are eligible. Children \> 14 years of age with a Karnofsky performance status of \> 60 are eligible.
• Children with normal organ and marrow function (as defined below) are eligible.
• hemoglobin ≥ 10 g/dL
• leukocytes \> 2000/mm3
• absolute neutrophil count (ANC) \>1,500/ mm3
• serum NA+, K+, BUN within institutional normal limits
• platelets \>75,000/ mm3
• total bilirubin \< 1.5 mg/dL
• AST(SGOT)/ALT(SGPT) \<3 times institutional upper limit of normal (ULN)

You may not qualify if:

• Children receiving prior ANP or TMZ therapy are not eligible.
• Children with an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, uncontrolled hypertension (\> grade 2) or psychiatric illness and/or social situations that would limit compliance with protocol study requirements are not eligible.
• Children with a history of congestive heart failure, deep venous thrombosis, or other cardiovascular or renal conditions that would contradict administration of high dose intravenous sodium or insertion of a subclavian venous catheter 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.

Sponsors & Collaborators

• Burzynski Research Institute: lead

Related Links

• Burzynski Research Institute
• Burzynski Clinic

MeSH Terms

Conditions

Optic Nerve Glioma; Recurrence

Interventions

Temozolomide; antineoplaston A10; antineoplaston AS 2-1

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Optic Nerve Neoplasms; Cranial Nerve Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Peripheral Nervous System Neoplasms; Cranial Nerve Diseases; Nervous System Diseases; Optic Nerve Diseases; Eye Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Stanislaw R Burzynski, MD, PhD

  Burzynski Research Institute

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2010
• First Posted: December 15, 2010
• Study Start: December 1, 2011
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2018
• Last Updated: July 26, 2017

Record last verified: 2017-07

Data Sharing

• IPD Sharing: Will not share