Neoplasms

All Conditions

Nervous System Diseases

Eye Diseases

Rare Diseases

Glioma

Optic Nerve Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Optic Nerve Neoplasms

Nervous System Neoplasms

Peripheral Nervous System Neoplasms

Cranial Nerve Diseases

Optic Nerve Diseases

Optic Pathway Glioma

Neuroepithelioma

Antineoplaston therapy (Atengenal + Astugenal) by IV infusion every four hours for at least 12 months. Study subjects receive increasing dosages of Atengenal and Astugenal until the maximum tolerated dose is reached.

Children with a visual pathway glioma, which is not amenable to standard therapy or has not responded to standard therapy, will receive Antineoplaston therapy (Atengenal + Astugenal).

Antineoplaston therapy (Atengenal + Astugenal)

Stanislaw R. Burzynski, MD, PhD

RATIONALE: Current therapies for children with visual pathway gliomas, which are not amenable to or have not responded to standard therapy, provide limited benefit to the patient. The anti-cancer properties of Antineoplaston therapy suggest that it may prove beneficial in the treatment of children with visual pathway gliomas, which are not amenable to or have not responded to standard therapy.

PURPOSE: This study is being performed to determine the effects (good and bad) that Antineoplaston therapy has on children with visual pathway gliomas, which are not amenable to or have not responded to standard therapy.

OBJECTIVES:

* To determine the efficacy of Antineoplaston therapy in children with visual pathway gliomas, which are not amenable to or have not responded to standard therapy, as measured by an objective response to therapy (complete response, partial response or stable disease).
* To determine the safety and tolerance of Antineoplaston therapy in children with visual pathway gliomas, which are not amenable to or have not responded to standard therapy.

OVERVIEW: This is a single arm, open-label study in which children with visual pathway gliomas, which are not amenable to or have not responded to standard therapy, receive gradually escalating doses of intravenous Antineoplaston therapy (Atengenal + Astugenal) until the maximum tolerated dose is reached. Treatment continues for at least 12 months in the absence of disease progression or unacceptable toxicity. After 12 months, patients with a complete or partial response or with stable disease may continue treatment.

To determine objective response, tumor size is measured utilizing MRI scans, which are performed every 8 weeks for the first two years, every 3 months for the third and fourth years, every 6 months for the 5th and sixth years, and annually thereafter.

PROJECTED ACCRUAL: Approximately 20-40 patients will be accrued to this study.

Antineoplaston Therapy in Treating Children With Visual Pathway Glioma

Phase II Study of Antineoplastons A10 and AS2-1 Infusions in Children With Visual Pathway Glioma

Objective response rate per Response Assessment in Neuro-Oncology (RANO) for target lesions and assessed by MRI: Complete Response (CR), disappearance of all disease sustained for at least four weeks; Partial Response (PR), \>=50% decrease in the sum of the products of of the greatest perpendicular diameters of all measurable enhancing lesions, sustained for at least four weeks. Stable Disease (SD): \<50% decrease in the sum of the products of of the greatest perpendicular diameters of all measurable enhancing lesions and no Progressive Disease, sustained for at least four weeks. Progressive Disease (PD): \>=25% increase in the sum of the products of of the greatest perpendicular diameters of all measurable enhancing lesions.

6 months, 12 months, 24 months, 36 months, 48 months, 60 months overall survival

Burzynski Research Institute

Adverse event data was collected through regular patient assessment and regular laboratory testing

Antineoplaston therapy (Atengenal + Astugenal) by IV infusion every four hours for at least 12 months. Study subjects receive increasing dosages of Atengenal and Astugenal until the maximum tolerated dose is reached.

Antineoplaston therapy (Atengenal + Astugenal): Patients with a visual pathway glioma will receive Antineoplaston therapy (Atengenal + Astugenal)

Antineoplaston Therapy

Antineoplaston therapy (Atengenal + Astugenal) by IV infusion every four hours for at least 12 months. Study subjects receive increasing dosages of Atengenal and Astugenal until the maximum tolerated dose is reached.

Antineoplaston therapy (Atengenal + Astugenal): Children with a visual pathway glioma, which is not amenable to standard therapy or has not responded to standard therapy, will receive Antineoplaston therapy (Atengenal + Astugenal).

Age, Continuous

Sex: Female, Male

S. R. Burzynski, MD, PhD

Complete Response

Partial Response

Stable Disease

Progressive Disease

Number of Participants With Objective Response

6 months overall survival

12 months overall survival

24 months overall survival

36 months overall survival

48 months overall survival

60 months overall survival

All study subjects receiving any Antineoplaston therapy

Percentage of Participants Who Survived

Overall Study

Diseases and Abnormalities at or Before Birth

Symptoms and General Pathology

Skin and Connective Tissue Diseases

Neurofibromatoses

Neurofibromatosis 1

Neurofibroma

Nerve Sheath Neoplasms

Syndrome

Neoplastic Syndromes, Hereditary

Neurocutaneous Syndromes

Heredodegenerative Disorders, Nervous System

Neurodegenerative Diseases

Genetic Diseases, Inborn

Peripheral Nervous System Diseases

Neuromuscular Diseases

Neurofibromatosis

Neurofibromatosis Type 1

Antineoplastic Agents

All Drugs and Chemicals

Carboplatin

Vincristine

Tubulin Modulators

Antimitotic Agents

INDUCTION: Patients receive carboplatin IV over 60 minutes on days 1, 8, 15, 22, 43, 50, 57, and 64 and vincristine IV or IV push over 1 minute on days 1, 8, 15, 22, 29, 36, 43, 50, 57, and 64 in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI during screening and on study.

MAINTENANCE: Patients receive carboplatin IV over 60 minutes on days 1, 8, 15, and 22 and vincristine IV or IV push over 1 minute on days 1, 8, and 15. Treatment repeats every 6 weeks for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI on study and during follow-up.

Patients receive selumetinib sulfate PO BID on days 1-28. Treatment is continuous and repeats every 28 days for 27 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI throughout the trial.

Magnetic Resonance Imaging

Quality-of-Life Assessment

Questionnaire Administration

Selumetinib Sulfate

Vincristine Sulfate

Site Public Contact

Joseph C. Torkildson

Lindsey M. Hoffman

David L. Becton

Albert Kheradpour

Nathan J. Robison

Aarati V. Rao

Elyssa M. Rubin

Jay Michael S. Balagtas

William D. Roberts

Yoko T. Udaka

Nicholas K. Foreman

Michael S. Isakoff

Asher M. Marks

Scott M. Bradfield

Jeffrey S. Dome

William B. Slayton

Iftikhar Hanif

Ziad A. Khatib

Fouad M. Hajjar

Jaime M. Libes-Bander

Jeffrey H. Schwartz

Stacie L. Stapleton

Jason R. Fangusaro

Wade T. Kyono

Martha M. Pacheco

Angela J. Waanders

Dipti S. Dighe

Wendy S. Darlington

Gregory P. Brandt

Sandeep Batra

Jessica F. Goodman

Samantha L. Mallory

David S. Dickens

James T. Badgett

Ashok B. Raj

Lolie C. Yu

Craig Lotterman

Daniel L. Callaway

Stanley Chaleff

Kenneth J. Cohen

David H. Ebb

Susan N. Chi

Andrea T. Franson

Hamza Gorsi

Kathleen J. Yost

Laura K. Gowans

Michael K. Richards

Christopher L. Moertel

Jonathan D. Schwartz

Betty L. Herrington

Barbara A. Gruner

Keith J. August

William S. Ferguson

Andrew S. Cluster

Jill C. Beck

Angela Ricci

Kathryn L. Laurie

Scott Moerdler

Xiaxin Li

Jessica M. Valdez

Lauren R. Weintraub

Matthew J. Barth

Mark P. Atlas

Elizabeth A. Raetz

David N. Korones

Melanie A. Comito

Jessica C. Hochberg

David E. Kram

Joel A. Kaplan

Jessica M. Sun

Andrea R. Whitfield

Thomas W. McLean

Samuel J. Milanovich

Erin Wright

Peter M. de Blank

Duncan S. Stearns

Mark A. Ranalli

Mukund G. Dole

Rene Y. McNall-Knapp

Jason M. Glover

Linda C. Stork

Jagadeesh Ramdas

Lisa M. McGregor

Michael J. Fisher

Gregory E. Halligan

James T. Felker

Jennifer J. Welch

Jacqueline M. Kraveka

Stuart L. Cramer

Aniket Saha

Susan E. Spiller

Ibrahim A. Qaddoumi

Jason R Fangusaro

This phase III trial studies if selumetinib works just as well as the standard treatment with carboplatin/vincristine (CV) for subjects with NF1-associated low grade glioma (LGG), and to see if selumetinib is better than CV in improving vision in subjects with LGG of the optic pathway (vision nerves). Selumetinib is a drug that works by blocking some enzymes that low-grade glioma tumor cells need for their growth. This results in killing tumor cells. Drugs used as chemotherapy, such as carboplatin and vincristine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether selumetinib works better in treating patients with NF1-associated low-grade glioma compared to standard therapy with carboplatin and vincristine.

PRIMARY OBJECTIVES:

I. To determine whether the efficacy of treatment with selumetinib sulfate (selumetinib) as measured by event-free survival (EFS) is non-inferior to treatment with carboplatin/vincristine sulfate (vincristine) (CV) in previously untreated neurofibromatosis type 1 (NF1)-associated low-grade glioma (LGG).

II. To determine whether visual acuity (VA) using Teller acuity cards (TAC), in patients with NF1-associated LGG within the optic pathway, is better in those treated with selumetinib compared to CV.

SECONDARY OBJECTIVES:

I. To estimate tumor response rates and overall survival (OS) in each treatment regimen in previously untreated NF1-associated LGG.

II. To evaluate VA outcomes utilizing HOTV letter acuity testing in previously untreated NF1-associated LGG within the optic pathway in patients who are old enough to perform visual acuity testing utilizing HOTV (a recognition acuity measure).

III. To describe the improvement in motor function as measured by the Vineland scale in patients with previously untreated NF1-associated LGG that have documented motor deficits at enrollment.

IV. To prospectively evaluate and compare the quality of life among patients treated with selumetinib or CV.

V. To prospectively evaluate and compare the cognitive, social, emotional, and behavioral functioning of patients with NF1-associated LGG treated with either selumetinib or CV.

EXPLORATORY OBJECTIVES:

I. To evaluate optical coherence tomography (OCT) measures of retinal axon and ganglion cell thickness as a marker of treatment response in previously untreated NF1-associated LGG within the optic pathway.

II. To compare novel, semi-automated volumetric magnetic resonance imaging (MRI) measures to traditional measurements of treatment response (bi-dimensional MRI measurements) in NF1-associated optic pathway tumors.

III. To obtain paired blood and tumor tissue to be banked for future NF1-LGG biology studies involving comprehensive molecular analysis, including but not limited to whole exome and ribonucleic acid (RNA) sequencing.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I:

INDUCTION: Patients receive carboplatin intravenously (IV) over 60 minutes on days 1, 8, 15, 22, 43, 50, 57, and 64 and vincristine IV or IV push over 1 minute on days 1, 8, 15, 22, 29, 36, 43, 50, 57, and 64 in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI during screening and on study.

MAINTENANCE: Patients receive carboplatin IV over 60 minutes on days 1, 8, 15, and 22 and vincristine IV or IV push over 1 minute on days 1, 8, and 15. Treatment repeats every 6 weeks for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI on study and during follow-up.

ARM II: Patients receive selumetinib sulfate orally (PO) twice daily (BID) on days 1-28. Treatment is continuous and repeats every 28 days for 27 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI throughout the trial.

After completion of study treatment, patients are followed up with MRIs and physical exams every 3 months for 1 year, every 6 months for 2 years, and then once yearly for up to 10 years.

A Study of the Drugs Selumetinib Versus Carboplatin/Vincristine in Patients With Neurofibromatosis and Low-Grade Glioma

A Phase 3 Randomized Study of Selumetinib Versus Carboplatin/Vincristine in Newly Diagnosed or Previously Untreated Neurofibromatosis Type 1 (NF1) Associated Low-Grade Glioma (LGG)

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page

cpRNFL thickness is a measure of optical coherence tomography (OCT). This assessment will be conducted in a subgroup of consenting patients with optic pathway gliomas (OPGs) treated at select COG institutions with the expertise to utilize this technology. Analysis will be conducted on a per-eye basis.

Data will be analyzed on a per-eye basis. Children with OPGs will be classified into decline in VA versus (vs.) stable/improved VA, depending on VA treatment response at 12 months. cpRNFL thickness prior to treatment initiation will be compared.

Data will be analyzed on a per-eye basis. Children with OPGs will be classified into decline in VA vs. stable/improved VA, depending on VA treatment response at 12 months. cpRNFL thickness change over time will be compared.

GCIPL thickness is another measure of optical coherence tomography (OCT). This assessment will be conducted in a subgroup of consenting patients with optic pathway gliomas (OPGs) treated at select COG institutions with the expertise to utilize this technology. Analysis will be conducted on a per-eye basis.

Data will be analyzed on a per-eye basis. Children with OPGs will be classified into decline in VA vs. stable/improved VA, depending on VA treatment response at 12 months. GCIPL thickness prior to treatment initiation will be compared.

Data will be analyzed on a per-eye basis. Children with OPGs will be classified into decline in VA vs. stable/improved VA, depending on VA treatment response at 12 months. GCIPL thickness change over time will be compared.

Optic pathway tumors will be classified into progressive disease (PD), stable disease (SD), partial response (PR), and complete response (CR) using novel semi-automated volumetric MRI measurements. This assessment will include patients with OPGs consenting to volumetric MRI study.

This assessment includes participants with OPGs consenting to volumetric MRI study.

EFS is defined as time from randomization to the first occurrence of any of the following events: clinical or radiographic disease progression, disease recurrence, second malignant neoplasm, or death from any cause. Patients who are event-free will be censored at the time of last follow-up. Hazard ratio based on a stratified Cox proportional hazards model will be reported, along with a 90% confidence interval.

VA will be assessed using Teller acuity cards (TAC). A significant improvement in VA will be defined as a decrease of \>= 0.2 logMAR (corrected for age) from baseline (pre-treatment baseline) to end of about 12 months of treatment. The primary analysis will be based on per subject outcome (rather than per eye).

Tumors will be classified into complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). Radiologic response rates will be summarized per arm and be tested for a difference between the two arms using an exact binomial test.

OS is defined as the time from randomization until death from any cause or till the time of last follow-up for patients who are alive at the time of analysis. Hazard ratio will be reported, along with a 90% confidence interval.

HOTV is a recognition acuity measure. It will be conducted on patients who are developmentally able to perform this testing.

The Vineland-3 Motor Scale from the Comprehensive Parent Rating Form will be used to assess motor deficits. Change in Vineland motor scale from baseline to about 12 months of treatment will be compared between two treatment arms.

Will be measured by Pain and Hurt subscale score. QOL will be assessed by Pediatric Quality of Life (PedsQL) Generic and Brain Tumor modules. Analysis will be based on a 2-sample t-test comparing change in Pain and Hurt subscale score from baseline to 12 months for the two arms.

Will be measured by Movement and Balance subscale score. QOL will be assessed by Pediatric Quality of Life (PedsQL) Generic and Brain Tumor modules. Analysis will be based on a 2-sample t-test comparing change in Movement and Balance subscale score from baseline to 12 months for the two arms.

Will be measured by BRIEF Cognitive Regulation Index (CRI). Executive function will be measured by age-appropriate Behavior Rating Inventory of Executive Function (BRIEF) questionnaire. Analysis will be based on a 2-sample t-test comparing change in the designated score from baseline to 24 months for the two arms.

Will be measured by Cogstate composite score. Neurocognitive function will be measured by a computerized battery (Cogstate) testing. Analysis will be based on a 2-sample t-test comparing change in Cogstate composite score from baseline to 24 months for the two arms.

National Cancer Institute (NCI)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Antineoplaston Therapy in Treating Children With Visual Pathway Glioma	NCT00003477	Visual Pathway ...	Antineoplaston ...	6 Months - 17 Years	Burzynski Research Institute
A Study of the Drugs Selumetinib Versus Carboplatin/Vincristine in Patients With Neurofibromatosis and Low-Grade Glioma	NCT03871257	Low Grade Gliom... Neurofibromatos... Visual Pathway ...	Carboplatin Magnetic Resona... Quality-of-Life... Questionnaire A... Selumetinib Sul... Vincristine Sul...	2 Years - 21 Years	National Cancer Institute (NCI)
A Study of the Drugs Selumetinib Versus Carboplatin/Vincristine in Patients With Neurofibromatosis and Low-Grade Glioma	NCT03871257	Low Grade Gliom... Neurofibromatos... Visual Pathway ...	Carboplatin Magnetic Resona... Quality-of-Life... Questionnaire A... Selumetinib Sul... Vincristine Sul...	2 Years - 21 Years	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for visual pathway glioma