Optic Nerve GliomaPhase 3NCT01260103
Phase 3 Study of ANP Therapy vs. TMZ for Optic Pathway Glioma
A Phase 3 study testing Temozolomide and ANP Therapy in people with Optic Nerve Glioma, run by Burzynski Research Institute.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 months to 18 years
- Conditions the study is for
- Optic Nerve Glioma
- What is being tested?
- Temozolomide and ANP Therapy
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Dec 2011to Dec 2018
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
- Children with or without prior RT are eligible.
- Histological confirmation of OPG is required unless the risks of obtaining a diagnostic biopsy are prohibitive.
- 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.
- 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.
- Children with a life expectancy of > 6 months are eligible.
Show all 18Show fewer
- 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 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.
- 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.
Who cannot join
- 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 psychiatric illness and/or social situations that would limit compliance with protocol study requirements are not eligible.
- 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.
- 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.
About this study
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
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:
Read more
- 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.
Read the detailed 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.
- Conditions
- Optic Nerve Glioma
- Being tested
- Temozolomide, ANP Therapy
- Keywords
- Optic pathway glioma, recurrent, Optic pathway glioma, progressive, Temozolomide, Temodar, TMZ, Antineoplastons, ANP therapy, Atengenal (A10), Astugenal (AS2-1)
- Medical subject headings
- Optic Nerve Glioma, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TemozolomideDrug
Also called Temodar, 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 for a maximum of 13 cycles.
ANP TherapyDrug
Also called Antineoplastons, Astengenal (A10), Astugenal (AS2-1)
Escalating doses of ANP therapy are administered for 52 weeks. If the study subject has an OR or maintains SD, ANP therapy is continued.
| Study group | Role | What they receive |
|---|---|---|
| Temozolomide (TMZ) | Active comparator | Study subjects receive TMZ for 13 cycles Receives: Drug: Temozolomide |
| ANP Therapy | Experimental | Escalating doses of ANP therapy are given daily for 52 weeks. Receives: Drug: ANP Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival (PFS)
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.
Measured: 5 years
Secondary outcomes (1)
Safety Analysis
Comparison of the toxicity profile for ANP therapy vs. the toxicity profile for TMZ will be accomplished using the Fisher's exact test.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2010 (estimated)
- Study startDec 2011
- Primary completionDec 2016 (estimated)
- Study completionDec 2018 (estimated)
Why it stopped: Withdrawn: study halted prematurely, prior to enrollment of first participant
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Optic Nerve GliomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Burzynski Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Stanislaw R Burzynski, MD, PhD, Study chair, Burzynski Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01260103
- Sponsor's protocol ID
- BRI-BT-54
- Status last verified
- Jul 2017
- First submitted
- 13 Dec 2010
- Last updated
- 26 Jul 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01260103
- Acronym / sponsor ID
- BRI-BT-54
- Conditions
- Optic Nerve Glioma
- Keywords
- Optic pathway glioma, recurrent, Optic pathway glioma, progressive, Temozolomide, Temodar, TMZ, Antineoplastons, ANP therapy, Atengenal (A10)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Withdrawn: study halted prematurely, prior to enrollment of first participant
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Burzynski Research InstituteUniversity, hospital or other
- Study start
- Dec 2011
- Primary completion
- Dec 2016 (estimated)
- Study completion
- Dec 2018 (estimated)
- First posted
- 15 Dec 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Temozolomide (TMZ) | Active comparator | Drug: TemozolomideStudy subjects receive TMZ for 13 cycles |
| ANP Therapy | Experimental | Drug: ANP TherapyEscalating doses of ANP therapy are given daily for 52 weeks. |
Who may qualify
- Ages
- 6 months to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (18 listed)
- 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.
- Children with or without prior RT are eligible.
- Histological confirmation of OPG is required unless the risks of obtaining a diagnostic biopsy are prohibitive.
- 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.
- 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.
Key exclusion criteria (4 listed)
- 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 psychiatric illness and/or social situations that would limit compliance with protocol study requirements are not eligible.
- 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.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TemozolomideAlso: Temodar, TMZStudy 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. | Drug | Temozolomide (TMZ) |
| ANP TherapyAlso: Antineoplastons, Astengenal (A10), Astugenal (AS2-1)Escalating doses of ANP therapy are administered for 52 weeks. If the study subject has an OR or maintains SD, ANP therapy is continued. | Drug | ANP Therapy |
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.
1 secondary outcome
Safety Analysis
Time frame: 5 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jul 2017.
- Burzynski Research InstituteLink provided by the sponsor.
- Burzynski ClinicLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stanislaw R Burzynski, MD, PhD study chair
Burzynski Research Institute
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Temozolomide and ANP Therapy in people with Optic Nerve Glioma, run by Burzynski Research Institute.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 26 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression free survival (PFS) (time frame: 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jul 2017.