Neoplasms

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Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Carboplatin

Vincristine

Tubulin Modulators

Antimitotic Agents

INDUCTION: Patients receive vincristine sulfate IV over 1 minute on days 1, 8, 15, 22, 29, 36, 43, 50, 57, and 64, and carboplatin IV over 60 minutes on days 1, 8, 15, 22, 43, 50, 57, and 64 in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and magnetic resonance imaging (MRI) at baseline and end of induction.

MAINTENANCE: Patients receive vincristine sulfate IV over 1 minute on days 1, 8, and 15, and carboplatin IV over 60 minutes on days 1, 8, 15, and 22. Treatment repeats every 42 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and undergo MRI at baseline, throughout the trial, and during follow up.

Patients receive selumetinib sulfate PO BID on days 1-28. Treatment repeats every 28 days for up to 27 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and undergo MRI at baseline, throughout the trial, and during follow up.

Biospecimen Collection

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

Fataneh (Fae) Majlessipour

Satiro N. De Oliveira

Aarati V. Rao

Elyssa M. Rubin

Jay Michael S. Balagtas

William D. Roberts

Alyssa T. Reddy

Jean M. Mulcahy Levy

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

Daniel L. Callaway

Stanley Chaleff

Kenneth J. Cohen

Allen I. Stering

David H. Ebb

Andrea T. Franson

Stephanie A. Toll

Kathleen J. Yost

Laura K. Gowans

Michael K. Richards

Christopher L. Moertel

Jonathan D. Schwartz

Betty L. Herrington

Keith J. August

William S. Ferguson

Andrew S. Cluster

Jill C. Beck

Kathryn L. Laurie

Lauren R. Weintraub

Matthew J. Barth

Chana L. Glasser

Mark P. Atlas

Elizabeth A. Raetz

Sameer Farouk Sait

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

Linda C. Stork

Jagadeesh Ramdas

Lisa M. McGregor

Michael J. Fisher

James T. Felker

Jennifer J. Welch

Jacqueline M. Kraveka

Stuart L. Cramer

Aniket Saha

Susan E. Spiller

Anna Vinitsky

Devang J. Pastakia

Shannon M. Cohn

Daniel C. Bowers

Benjamin Carcamo

Sibo Zhao

Murali M. Chintagumpala

Najat C. Daw

Peter M de Blank

This phase III trial compares the effect of selumetinib versus the standard of care treatment with carboplatin and vincristine (CV) in treating patients with newly diagnosed or previously untreated low-grade glioma (LGG) that does not have a genetic abnormality called BRAFV600E mutation and is not associated with systemic neurofibromatosis type 1. Selumetinib works by blocking some of the enzymes needed for cell growth and may kill tumor cells. Carboplatin and vincristine are chemotherapy drugs that work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. The overall goal of this study is to see if selumetinib works just as well as the standard treatment of CV for patients with LGG. Another goal of this study is to compare the effects of selumetinib versus CV in subjects with LGG to find out which is better. Additionally, this trial will also examine if treatment with selumetinib improves the quality of life for subjects who take it.

PRIMARY OBJECTIVE:

I. To demonstrate that the efficacy of treatment with selumetinib as measured by event-free survival (EFS) is non-inferior compared to treatment with carboplatin/vincristine (CV) in previously-untreated low-grade glioma (LGG) not associated with BRAFV600E mutations or systemic neurofibromatosis type 1 (NF1).

SECONDARY OBJECTIVES:

I. To estimate tumor response rates to each regimen of chemotherapy. II. To evaluate visual acuity (VA) outcomes utilizing Teller Acuity Cards (TAC) and HOTV letter acuity testing in previously-untreated optic pathway gliomas (OPGs).

III. To describe the improvement in motor function as measured by the Vineland Scale in children with previously-untreated LGG that have motor deficits at enrollment.

IV. To estimate the difference in EFS and tumor response rate between BRAF rearranged and non-BRAF rearranged patients treated on each chemotherapy regimen.

V. To prospectively evaluate the quality of life of children with LGG not associated with BRAFV600E or systemic NF1 treated with either CV or selumetinib.

VI. To prospectively evaluate the cognitive, social, emotional, and behavioral functioning of children with LGG not associated with BRAFV600E or systemic NF1 treated with either CV or selumetinib.

EXPLORATORY OBJECTIVE:

I. To obtain paired blood and tumor specimens for future biology studies, including studies to correlate genomic drivers to response.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I:

INDUCTION: Patients receive vincristine sulfate intravenously (IV) over 1 minute on days 1, 8, 15, 22, 29, 36, 43, 50, 57, and 64, and carboplatin IV over 60 minutes on days 1, 8, 15, 22, 43, 50, 57, and 64 in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and magnetic resonance imaging (MRI) at baseline and end of induction.

MAINTENANCE: Patients receive vincristine sulfate IV over 1 minute on days 1, 8, and 15, and carboplatin IV over 60 minutes on days 1, 8, 15, and 22. Treatment repeats every 42 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and undergo MRI at baseline, throughout the trial, and during follow up.

ARM II: Patients receive selumetinib sulfate orally (PO) twice daily (BID) on days 1-28. Treatment repeats every 28 days for up to 27 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and undergo MRI at baseline, throughout the trial, and during follow up.

After completion of study treatment, patients are followed up every 3 months for year 1, every 6 months for years 2-3, and then annually for years 4-10.

A Study of the Drugs Selumetinib vs. Carboplatin and Vincristine in Patients With Low-Grade Glioma

A Phase 3 Randomized Non-Inferiority Study of Carboplatin and Vincristine Versus Selumetinib (NSC# 748727) in Newly Diagnosed or Previously Untreated Low-Grade Glioma (LGG) Not Associated With BRAFV600E Mutations or Systemic Neurofibromatosis Type 1 (NF1)

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.

QOL scores for each domain of the PedsQL Generic module will be summarized by timepoint (4 timepoints) and treatment arm. Mean QOL scores will be reported with standard deviations. If scores do not follow normal distributions, medians and ranges will be reported instead.

Neurocognitive functioning scores for each index/scale of the Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2) will be summarized by timepoint (4 timepoints) and treatment arm. Mean scores will be reported with standard deviations. If scores do not follow normal distributions, medians and ranges will be reported instead.

The Kaplan-Meier method will be used to estimate EFS which is defined as the interval from randomization to first occurrence of clinical or radiographic disease progression, disease recurrence, second malignant neoplasm, or death from any cause, or to the date of last follow-up. Estimates with 95% confidence intervals will be reported by treatment arm. The hazard ratio with a confidence interval will also be reported to compare treatment arms based on a Cox proportional hazards model stratified by BRAF status, tumor location and size of residual tumor.

Percentages of patients with responses (complete or partial response) will be reported by treatment arm with 95% confidence intervals. The result of an exact binomial test to test for the difference in response rates between treatment arm will also be reported.

The Kaplan-Meier method will be used to estimate OS by treatment arm, defined as the interval from randomization to death from any cause, or to the date of last follow-up. Estimates with confidence intervals will be reported by treatment arm.

Numbers of patients that show improvement in VA after 12 months of treatment will be reported by treatment arm. Patients with at least 1 impaired eye are evaluable. In a patient with a unilateral optic nerve glioma, only the affected eye is considered. In patients with bilateral visual impairment, if VA improves in 1 eye but worsens in the other, the patient will be coded as a treatment failure, whereas if 1 eye improves and the other is at least stable, the patient will be coded as a success.

Motor function is measured using the Vineland-3 Motor Scale. Only patients with motor function deficits at baseline are included. Magnitudes of change for each patient after 48 weeks of therapy from baseline will be calculated and medians (with ranges) by treatment arm will be reported.

QOL will be measured using the PedsQL Total Scale Score as measured from the validated PedsQL Generic Module (for children 2-21 years old). Mean differences in the total scale score between 9 months and baseline will be reported by treatment arm. The results of 2-sample t-test comparing differences in the QOL scores between the 2 arms will also be reported. If change scores do not follow normal distributions, non-parametric alternatives may be employed for analysis.

Measured by Wechsler Processing Speed Index (standard score). Scores at 9 months will be summarized by treatment arm and reported as means (with standard deviations) or medians (with ranges) depending on the data distribution.

Executive function will be measured by the BRIEF-2 Cognitive Regulation Index (CRI). Summary statistics for the differences in scores from baseline to 9 months will be reported by treatment arm.

National Cancer Institute (NCI)

Symptoms and General Pathology

Blood and Lymph Conditions

Immune System Diseases

Gland and Hormone Related Diseases

Musculoskeletal Diseases

Eye Diseases

Recurrence

Glioblastoma

Brain Neoplasms

Meningioma

Oligodendroglioma

Lymphoma

Pituitary Diseases

Germinoma

Pituitary Neoplasms

Craniopharyngioma

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Disease Attributes

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

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Anaplastic Oligoastrocytoma

Pharmaceutical Solutions

Dermatologic Agents

Central Nervous System Depressants

Immunomodulating Agents

Dihematoporphyrin Ether

Trioxsalen

Hematoporphyrin Derivative

Ether

Photosensitizing Agents

Photofrin photodynamic therapy. Drug - 2.5 mg/kg, light - 240 mJ/cm2.

The subjects will receive a dose of 2.5 mg/kg of Photofrin intravenously 24 hours before planned surgical resection. Tumor resection will be carried out in the standard fashion in order to achieve the maximum tumor resection compatible with preservation of neurological function. After resection, Intralipid will be infused into the craniotomy and kept for approximately 45 min, while PDT will be performed. The illumination time will be calculated from the power density (mW) emitted by the laser and the radius (r) of the cavity to deliver a total light dose of 240 J/cm2 at a using the following formula:

Treatment Time (sec) = Light dose (J/cm2) x Cavity surface (cm2) x 1000 Power density (mW) Cavity Surface (cm2) = 4 x 3.14 x r2 The optical fiber will be placed in the center of the surgical cavity and photoillumination will commence. After PDT, the Intralipid solution will be removed and the wound will be closed. The subject will be sent to the intensive care area for recovery.

Photofrin photodynamic therapy.

Harry T Whelan, MD

This study will be aimed at investigating the effectiveness of a treatment for brain tumors called Photodynamic Therapy, or PDT. Briefly, a subject will receive a light-sensitive drug, called Photofrin®, the day before a tumor removal surgery. The next day, after the tumor is removed, red light from a laser will be shone into the tumor cavity through a light-diffusing sphere. This light will activate the photosensitizer, and possibly kill any tumor cells that may be left.

We plan to measure how long the subject may go without a new tumor regrowth, and overall how long subjects survive. We will compare these results to typical results to see if we are seeing any improvements.

Objective: To define the antitumor activity of Photofrin® and laser light activation within the confines of a Phase II study.

Photodynamic therapy (PDT) is a well-known treatment for other type of tumors; however it is an experimental treatment for brain tumors. There is much we do not know about the effectiveness of PDT in patients with brain tumors. The purpose of this study is to define the antitumor activity of Photofrin® and laser light activation. Photofrin® is a photosensitizing drug (a dye that is activated by light) used in PDT. We want to test the activity of PDT and to see what are the effects (good and bad) on you and your brain tumor. We also want to learn if this treatment will cause brain tumors to shrink and whether it will help patients with brain tumors to live longer.

PDT is a cancer treatment that involves giving a photosensitive dye (Photofrin®), into your vein through a tube (called an IV). This dye will go inside of the cancer cells more than it will go inside the normal, healthy cells. PDT using Photofrin® is an approved treatment in patients with certain types of cancer such as lung, and esophageal (from the mouth to the stomach) cancers.

Everyone in this study will receive Photofrin® (porfimer sodium) for injection (Pinnacle Biologics, Inc., Bannockburn, IL, USA), and be treated with red light emitted by a red laser. The light will be sent from the laser to the surface of the brain where the tumor is located using a light transmitting fiber. The fiber will have a knob at the end that spreads the light out evenly in all directions.

Previous studies have shown that patients with malignant brain tumors called gliomas had a good response to PDT. The patients in these studies lived longer than they were expected to live. In one study of adults with brain tumors in Australia, patients given PDT had greatly improved survival rates. Fifty seven percent (57%) of the patients with gliomas called anaplastic astrocytoma survived for 36 months. Thirty seven percent (37%) of the patients with gliomas called glioblastoma multiforme survived for 36 months. Froedtert Hospital, in Milwaukee WI, has been involved in PDT studies in adults in the past. This current study is is being done in a very similar way to the study done in Australia, and will use increased Photofrin®) and light doses than our previous study.

Photodynamic Therapy (PDT) For Recurrent High Grade Gliomas

A Phase II Study of Photodynamic Therapy (PDT) With Photofrin® (IND 104,613) For Recurrent High Grade Gliomas in Adults

Relapse free survival is the proportion of subjects who have gone six months since PDT without the disease getting worse.

To obtain preliminary data toward determining whether this combination results in higher remission rate when compared to historical data.

To further explore and report progression-free survival and overall survival for three years post PDT treatment.

To measure complete response, partial response, stable disease or progressive disease using the response assessment for Neuro-Oncology (RANO) criteria with the follow-up medical imaging, which specifically incorporates volumetric measurements of brain tumor enhancement and clinical measures of neurological decline and to compare these outcomes to historical controls.

Pinnacle Biologics Inc.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of the Drugs Selumetinib vs. Carboplatin and Vincristine in Patients With Low-Grade Glioma	NCT04166409	Low Grade Astro... Low Grade Gliom... Metastatic Low ... Metastatic Low ...	Biospecimen Col... Carboplatin Magnetic Resona... Quality-of-Life... Questionnaire A... Selumetinib Sul... Vincristine Sul...	2 Years - 21 Years	National Cancer Institute (NCI)
Photodynamic Therapy (PDT) For Recurrent High Grade Gliomas	NCT01966809	Brain Tumor, Re...	Photofrin photo...	18 Years -	Medical College of Wisconsin
Photodynamic Therapy (PDT) for Recurrent Pediatric Brain Tumors	NCT01682746	Brain Tumor, Re...	Photofrin (porf...	6 Months - 18 Years	Medical College of Wisconsin
Photodynamic Therapy (PDT) for Recurrent Pediatric Brain Tumors	NCT01682746	Brain Tumor, Re...	Photofrin (porf...	6 Months - 18 Years	Medical College of Wisconsin
Photodynamic Therapy (PDT) for Recurrent Pediatric Brain Tumors	NCT01682746	Brain Tumor, Re...	Photofrin (porf...	6 Months - 18 Years	Medical College of Wisconsin

Spots Global Cancer Trial Database for low grade astrocytoma