Phase 3 Study of ANP Therapy vs. TMZ for Optic Pathway Glioma
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.
- 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.
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Randomized Phase 3 Study of Combination Antineoplaston Therapy [Antineoplastons A10 (Atengenal) and AS2-1 (Astugenal)] vs. Temozolomide in Subjects With Recurrent and / or Progressive Optic Pathway Glioma After Carboplatin or Cisplatin Therapy|
- Progression free survival (PFS) [ Time Frame: 5 years ] [ Designated as safety issue: No ]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.
- Safety Analysis [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]Comparison of the toxicity profile for ANP therapy vs. the toxicity profile for TMZ will be accomplished using the Fisher's exact test.
|Study Start Date:||December 2011|
|Estimated Study Completion Date:||December 2018|
|Estimated Primary Completion Date:||December 2016 (Final data collection date for primary outcome measure)|
Active Comparator: Temozolomide (TMZ)
Study subjects receive TMZ for 13 cycles
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.
Experimental: ANP Therapy
Escalating doses of ANP therapy are given daily for 52 weeks.
Drug: ANP Therapy
Escalating doses of ANP therapy are administered for 52 weeks. If the study subject has an OR or maintains SD, ANP therapy is continued.