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

Phase

Condition

Brain Tumor

Brain Cancer

Astrocytoma

Treatment

N/A

Clinical Study ID

NCT01260103

BRI-BT-54

Ages 6-18
All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

Children age ≥ 6 months < 18 years are eligible if they have 1) received priortreatment with carboplatin or cisplatin, which was terminated secondary to toxicity orprogression of OPG or 2) developed recurrence of OPG after completion of carboplatinor cisplatin therapy.
Children with or without prior RT are eligible.
Histological confirmation of OPG is required unless the risks of obtaining adiagnostic biopsy are prohibitive.
Evidence of OPG (≥ 5 mm), as diagnosed by MRI of the brain, with and withoutgadolinium contrast, within four weeks of protocol study entry is required. The MRI isinterpreted by two independent neuroradiologists. If there is disagreement, a thirdindependent neuroradiologist will adjudicate. Baseline MR spectroscopy (MRS) andpositron emission tomography (PET) scan are also performed.
Children who are receiving corticosteroids and, for at least one week prior to entryinto the protocol study have been on the lowest dose of corticosteroids that preservesoptimal 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)
serum creatinine < 1.5 mg/dL

At the recommended therapeutic dose, the effects of ANP therapy on the developinghuman fetus are unknown. For this reason, women of child-bearing potential who agreeto use adequate contraception (hormonal or barrier method of birth control;abstinence) prior to protocol study entry and for the duration of protocol study areeligible. Should a woman become pregnant or suspect she is pregnant whileparticipating in this protocol study, she will inform her treating physicianimmediately.
Children who are able to understand a written informed consent document, and arewilling to sign it, are eligible. A subject with a parent or guardian who is able tounderstand a written informed consent document, and who is willing to sign it on thesubject's behalf, is eligible.

Exclusion

Exclusion Criteria:

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 psychiatricillness and/or social situations that would limit compliance with protocol studyrequirements are not eligible.
Children with a history of congestive heart failure, deep venous thrombosis, or othercardiovascular or renal conditions that would contradict administration of high doseintravenous sodium or insertion of a subclavian venous catheter are not eligible.
Pregnant women are not eligible because the teratogenic and abortifacient effects ofANP therapy in humans are unknown. Because there is an unknown but potential risk foradverse events in nursing infants secondary to the mother receiving ANP therapy,breastfeeding is discontinued if the mother receives ANP therapy.

Study Design

December 01, 2011

December 31, 2018

Study Description

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 sample size in the Phase 2 study is small and may overstate the effect of ANP therapy in general use, a hazard of 0.167 per year was utilized in determining the sample size for the proposed Phase 3 protocol study, giving a hazard ratio (TMZ:ANP) of 2.0.

The primary efficacy hypothesis of the proposed protocol study is that ANP therapy provides for a significantly better PFS than does TMZ. This protocol study is event-driven (PD or death from any cause), and will be completed after 90 events have occurred. The required sample size in each treatment group is 79.

A log rank test of equality of survival curves, with a 0.05 two-sided significance level, has 90% power to detect the difference in PFS between children treated with ANP therapy vs. children treated with TMZ. Assuming an accrual rate of 4 subjects per month, the accrual period is 3 years and 3 months. There is an additional 3 years of follow-up. A common exponential dropout rate of 0.05 per year is assumed.

This study utilizes an intention-to-treat (ITT) analysis. It is event-driven (PD or death from any cause), and will be completed after 90 events have occurred. All subjects are evaluable for PFS from the time of randomization to the time of PD or death, regardless of therapy group, eligibility, or adequacy of follow-up. All study subjects who receive at least one dose of ANP therapy or TMZ are evaluable for safety.

Connect with a study center

Burzynski Research Institute, Inc
Houston, Texas 77055
United States
Site Not Available

Not the study for you?

Let us help you find the best match. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.