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

Study Status: Withdrawn
Recruit Status: Withdrawn
Study Type: Interventional

Official Title: A Randomized Phase 3 Study of Antineoplastons A10 and AS2-1 vs. Temozolomide in Subjects With Recurrent and / or Progressive Optic Pathway Glioma After Carboplatin or Cisplatin Therapy

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 treate

    Detailed Summary:

    This is a randomized, phase 3, open-label, multicenter, protocol study in children age ≥ 6 months to < 18 yr., with recurrent and/or progressive OPG who 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. A total of 158 subjects will be enrolled and randomized equally to one of two therapy groups: ANP therapy (79 subjects) or TMZ (79 subjects). If an average of 4 subjects is enrolled each month, enrollment will be completed in 3 years and 3 months. There will be an additional three years of follow-up.

    Children of either gender and from all racial/ethnic groups will be eligible for this protocol study if they meet the criteria outlined in Section 3. Upon determination of eligibility, including the obtaining of an informed consent, study subjects will be randomized to ANP therapy or TMZ. The randomization will be stratified by prior RT (Y/N), hypothalamic involvement (Y/N) and age (< 5 years / ≥ 5 years).

    In a group of children treated with TMZ after developing progressive and/or recurrent disease following first-line chemotherapy, a 2-year PFS of 49% and a 4-year PFS of 31% was reported by Gururangan and associates. Based on their results, and assuming an exponential distribution, a least squares estimate of the hazard is 0.333 per year.

    For those study subjects, in the BRI Phase 2 study of ANP therapy for OPG, who 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, a least squares estimate of the hazard is 0.075 per year. Since the sam
    Sponsor: Burzynski Research Institute

    Current Primary Outcome: Progression free survival (PFS) [ Time Frame: 5 years ]

    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.


    Original Primary Outcome: Progression free survival (PFS) [ Time Frame: 4 years ]

    Comparison of the 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.


    Current Secondary Outcome: Safety Analysis [ Time Frame: 5 years ]

    Comparison of the toxicity profile for ANP therapy vs. the toxicity profile for TMZ will be accomplished using the Fisher's exact test.


    Original Secondary Outcome: Toxicity profile for Antineoplastons (ANP) therapy vs. Temozolomide (TMZ). [ Time Frame: 104 weeks ]

    The safety analysis will include adverse event (AE) data from all randomized study subjects who receive at least one dose of ANP therapy or one dose of TMZ. All AEs will be categorized according to CTCAE v3.0 (type and severity). Serum sodium concentration abnormalities will also be described by clinical criteria. Comparison of the toxicity profiles for ANP therapy vs. TMZ will be accomplished using the Fisher's exact test.


    Information By: Burzynski Research Institute

    Dates:
    Date Received: December 13, 2010
    Date Started: December 2011
    Date Completion: December 2018
    Last Updated: December 5, 2016
    Last Verified: December 2016