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

• Status: Withdrawn
• Trial end date: 2018-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Burzynski Research Institute
• Treatments: Dacarbazine; Temozolomide

Criteria

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.