A Randomized Study of Antineoplaston Therapy vs. Temozolomide in Subjects With Recurrent and / or Progressive Optic Pathway Glioma

The purpose of this study is 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.

• Drug: Temozolomide
  Study subjects in a fasting state receive temozolomide (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
  Other Names:

  • Temodar
  • TMZ
• Drug: Antineoplaston A10 and Antineoplaston AS2-1 (ANP)

  A central venous catheter is placed prior to initiation of ANP therapy. ANP therapy is administered via a dual channel infusion pump. The infusion pump is programmed once every 24 hours with the daily doses of A10 and AS2-1 being divided into six infusions, at 4-hourly intervals.

  ANP therapy administration is according to the following schedule:

  Day 1: The starting (loading) dose for A10 is 60 mL/day (300 mg/mL) and for AS2-1 is 60 mL (80 mg/mL).

  Day 2: A10 is administered at 7 mL/kg/day (2.1 g/kg/day), while AS2-1 is administered at 5 mL/kg/day (0.4 g/kg/day).

  Day 3 and subsequent days: The A10 dose is increased by 7 mL/kg/day (2.1 g/kg/day) daily until the maximum tolerated dose is reached, not exceeding 70 mL/kg/day (21 g/kg/day).

  Other Names:

  • Atengenal
  • Astugenal

• Active Comparator: Temozolomide (TMZ)

  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 to a maximum of 26 cycles.

  Intervention: Drug: Temozolomide
• Experimental: Antineoplastons (ANP)
  Combination antineoplaston therapy: [Antineoplaston A10 (Atengenal) and Antineoplaston AS2-1 (Astugenal)] given six times daily (open label) by subclavian vein infusion.
  Intervention: Drug: Antineoplaston A10 and Antineoplaston AS2-1 (ANP)

Inclusion Criteria:

1. 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.
2. Children with or without prior RT are eligible.
3. Histological confirmation of OPG is required unless the risks of obtaining a diagnostic biopsy are prohibitive.
4. 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.
5. 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.
6. Children with a life expectancy of > 6 months are eligible.
7. 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.

8. 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)
   • serum creatinine < 1.5 mg/dL
9. At the recommended therapeutic dose, the effects of ANP therapy on the developing human fetus are unknown. For this reason, women of child-bearing potential who agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to protocol study entry and for the duration of protocol study are eligible. Should a woman become pregnant or suspect she is pregnant while participating in this protocol study, she will inform her treating physician immediately.
10. Children who are able to understand a written informed consent document, and are willing to sign it, are eligible. A subject with a parent or guardian who is able to understand a written informed consent document, and who is willing to sign it on the subject's behalf, is eligible.

Exclusion Criteria:

1. Children receiving prior ANP or TMZ therapy are not eligible.
2. 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.
3. 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.
4. 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.