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AzTrials

Recurrent Low Grade AstrocytomaPhase 3NCT04576117

A Study to Compare Treatment With the Drug Selumetinib Alone Versus Selumetinib and Vinblastine in Patients With Recurrent or Progressive Low-Grade Glioma

A Phase 3 study testing Biospecimen Collection, Magnetic Resonance Imaging and Quality-of-Life Assessment in people with Recurrent Low Grade Astrocytoma and Recurrent WHO Grade 2 Glioma, run by National Cancer Institute (NCI) at 101 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This phase III trial investigates the best dose of vinblastine in combination with selumetinib and the benefit of adding vinblastine to selumetinib compared to selumetinib alone in treating children and young adults with low-grade glioma (a common type of brain cancer) that has come back after prior treatment… Read more about this study

Who is it for?
Ages 2 to 25 years
What is being tested?
Biospecimen Collection, Magnetic Resonance Imaging and Quality-of-Life Assessment
Could I receive a placebo?
No, everyone receives an active treatment
How many people
300 participants
Where
101 sitesin 2 countries
Study dates
16 Feb 2021to 30 Dec 2026
Phase
Phase 3
Are there results?
Not yet: the study is under way

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 2 to 25 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Feasibility phase: patients must be >= 2 years and =< 21 years of age at the time of enrollment
  • Efficacy phase: patients must be >= 2 years and =< 25 years of age at the time of enrollment
  • All patients > 21 years of age at the time of enrollment must have had initial diagnosis of low-grade glioma by 21 years of age
  • Patients must have a body surface area (BSA) of >= 0.5 m^2 at enrollment
  • Patients must have eligibility confirmed by rapid central pathology and central molecular screening reviews performed on APEC14B1
  • Non-neurofibromatosis type 1 (non-NF1), non-tuberous sclerosis complex (non-TSC) low-grade glioma (LGG) without a BRAFV600E or IDH1 mutation
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  • Patients must have progressive or recurrent LGG. Note: Biopsy may be at either initial diagnosis or recurrence
  • Patients must have measurable disease, defined as having a two-dimensional measurable tumor volume of >= 1 cm^2
  • Tumor size will be measured to include both solid and cystic components of the tumor (whether or not tumor is enhancing) + fluid attenuated inversion recovery (FLAIR) signal
  • Eligible histologies will include all tumors considered low-grade glioma or low-grade astrocytoma (World Health Organization [WHO] grade 1 and II) by the WHO Classification of Tumors of the Central Nervous System - 4th Edition Revised, with the exception of subependymal giant cell astrocytoma
  • Patients with metastatic disease or multiple independent primary LGGs are eligible
  • Patients must be progressive or recurrent after having been treated with at least one prior tumor-directed therapy before enrollment
  • Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
  • Myelosuppressive chemotherapy: Must not have received within 2 weeks of entry onto this study (4 weeks if prior nitrosourea);
  • Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent;
  • Radiation therapy (RT): >= 2 weeks (wks) for local palliative RT (small port); >= 6 months must have elapsed if prior craniospinal RT or if >= 50% radiation of pelvis; >= 6 wks must have elapsed if other substantial bone marrow (BM) radiation;
  • Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to =< grade 1;
  • MEK inhibitor or vinblastine: Must not have received treatment with a MEK inhibitor or vinblastine within 6 months of study enrollment
  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^ 2 or a serum creatinine based on age/sex as follows (within 7 days prior to enrollment):
  • 2 to < 6 years: 0.8 mg/dL (male) 0.8 mg/dL (female)
  • 6 to < 10 years: 1 mg/dL (male) 1 mg/dL (female)
  • 10 to < 13 years: 1.2 mg/dL (male) 1.2 mg/dL (female)
  • 13 to < 16 years: 1.5 mg/dL (male) 1.4 mg/dL (female)
  • >= 16 years: 1.7 mg/dL (male) 1.4 mg/dL (female)
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment) (children with a diagnosis of Gilbert's syndrome will be allowed on study regardless of their total and indirect [unconjugated] bilirubin levels as long as their direct [conjugated] bilirubin is < 3.1 mg/dL)
  • Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L (within 7 days prior to enrollment)
  • Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L
  • Albumin >= 2 g/L (within 7 days prior to enrollment)
  • Left ventricular ejection fraction (LVEF) >= 53% (or institutional normal; if the LVEF result is given as a range of values, then the upper value of the range will be used) by echocardiogram (within 4 weeks prior to enrollment)
  • Corrected QT interval (QTc interval) =< 450 msec by electrocardiogram (EKG) (within 4 weeks prior to enrollment)
  • Absolute neutrophil count >= 1,000/uL (unsupported) (within 7 days prior to enrollment)
  • Platelets >= 100,000/uL (unsupported) (within 7 days prior to enrollment)
  • Hemoglobin >= 8 g/dL (may be supported) (within 7 days prior to enrollment)
  • Patients with a known seizure disorder should be stable and should not have experienced a significant increase in seizure frequency within 2 weeks prior to enrollment
  • Stable neurological examination for >= 1 week
  • HYPERTENSION:
  • Patients 2-17 years of age must have a blood pressure that is =< 95th percentile for age, height, and sex at the time of enrollment (with or without the use of anti-hypertensive medications);
  • Patients >= 18 years of age must have a blood pressure =< 130/80 mmHg at the time of enrollment (with or without the use of anti-hypertensive medications)
  • Note for patients of all ages: Adequate blood pressure can be achieved using medication for the treatment of hypertension
  • All patients must have ophthalmology toxicity assessments performed within 4 weeks prior to enrollment
  • For all patients, an MRI of the brain (with orbital cuts for optic pathway tumors) and/or spine (depending on the site[s] of primary disease) with and without contrast must be performed within 4 weeks prior to enrollment
  • Note: If surgical resection or biopsy is performed at the time of progression or recurrence, a post-operative MRI is required
  • Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2. Use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age
  • Patients must have the ability to swallow whole capsules

Who cannot join

  • Prior therapy with vinblastine and/or a MEK inhibitor is permitted, with the following exceptions:
  • Patients must not have had progressive disease while on therapy with vinblastine or a MEK inhibitor;
  • Patients must not have discontinued vinblastine or selumetinib due to toxicity
  • Patients with a concurrent malignancy or history of treatment (other than surgery) for another tumor within the last year are ineligible
  • Patients with diffuse intrinsic pontine tumors as seen on MRI (> 2/3 of pons involvement on imaging) are not eligible even if biopsy reveals grade I/II histology
  • Patients may not be receiving any other investigational agents
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  • Patients must not have known hypersensitivity to selumetinib, vinblastine, or similar compounds
  • CYP3A4 agents: Patients must not have received fluconazole or drugs that are strong inducers or inhibitors of CYP3A4 within 7 days prior to study enrollment
  • Patients with any serious medical or psychiatric illness/condition, including substance use disorders or ophthalmological conditions, likely in the judgment of the investigator to interfere or limit compliance with study requirements/treatment
  • Patients who, in the opinion of the investigator, are not able to comply with the study procedures are not eligible
  • PRE-EXISTING CONDITIONS (CARDIAC):
  • Known genetic disorder that increases risk for coronary artery disease. Note: The presence of dyslipidemia in a family with a history of myocardial infarction is not in itself an exclusion unless there is a known genetic disorder documented;
  • Symptomatic heart failure
  • New York Heart Association (NYHA) class II-IV prior or current cardiomyopathy
  • Severe valvular heart disease
  • History of atrial fibrillation
  • PRE-EXISTING CONDITIONS (OPHTHALMOLOGIC CONDITIONS):
  • Current or past history of central serous retinopathy
  • Current or past history of retinal vein occlusion or retinal detachment
  • Patients with uncontrolled glaucoma
  • If checking pressure is clinically indicated, patients with intraocular pressure (IOP) > 22 mmHg or upper limit of normal (ULN) adjusted by age are not eligible
  • Any multivitamin containing vitamin E must be stopped prior to study enrollment even if it contains less than 100% of the daily recommended dosing for vitamin E
  • Surgery within 2 weeks prior to enrollment, with the exception of a surgical biopsy, placement of a vascular access device or cerebrospinal fluid (CSF) diverting procedure such as endoscopic third ventriculostomy (ETV) and ventriculoperitoneal (VP) shunt
  • Note: Patients must have healed from any prior surgery
  • Patients who have an uncontrolled infection are not eligible
  • Female patients who are pregnant are not eligible since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential
  • Lactating females who plan to breastfeed their infants
  • Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation and for 12 weeks after stopping study therapy are not eligible
  • Note: Women of child-bearing potential and males with sexual partners who are pregnant or who could become pregnant (i.e., women of child-bearing potential) should use effective methods of contraception for the duration of the study and for 12 weeks after stopping study therapy to avoid pregnancy and/or potential adverse effects on the developing embryo
  • All patients and/or their parents or legal guardians must sign a written informed consent
  • All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Trial locations and contacts

101 sites in 2 countries.

101 sites in 2 countries

United States91 sites

  • Children's Hospital Medical Center of Akron

    Akron, Ohio, 44308

  • Albany Medical Center

    Albany, New York, 12208

  • University of New Mexico Cancer Center

    Albuquerque, New Mexico, 87106

  • C S Mott Children's Hospital

    Ann Arbor, Michigan, 48109

  • Children's Healthcare of Atlanta - Arthur M Blank Hospital

    Atlanta, Georgia, 30329

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

  • Dell Children's Medical Center of Central Texas

    Austin, Texas, 78723

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • Walter Reed National Military Medical Center

    Bethesda, Maryland, 20889-5600

  • Children's Hospital of Alabama

    Birmingham, Alabama, 35233

  • Saint Luke's Cancer Institute - Boise

    Boise, Idaho, 83712

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • Carolinas Medical Center/Levine Cancer Institute

    Charlotte, North Carolina, 28203

  • Lurie Children's Hospital-Chicago

    Chicago, Illinois, 60611

  • University of Illinois

    Chicago, Illinois, 60612

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • Prisma Health Richland Hospital

    Columbia, South Carolina, 29203

  • Nationwide Children's Hospital

    Columbus, Ohio, 43205

  • UT Southwestern/Simmons Cancer Center-Dallas

    Dallas, Texas, 75390

  • Dayton Children's Hospital

    Dayton, Ohio, 45404

  • Children's Hospital of Michigan

    Detroit, Michigan, 48201

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Sanford Broadway Medical Center

    Fargo, North Dakota, 58122

  • Golisano Children's Hospital of Southwest Florida

    Fort Myers, Florida, 33908

  • Cook Children's Medical Center

    Fort Worth, Texas, 76104

  • UF Health Cancer Institute - Gainesville

    Gainesville, Florida, 32610

  • Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital

    Grand Rapids, Michigan, 49503

  • East Carolina University

    Greenville, North Carolina, 27834

  • BI-LO Charities Children's Cancer Center

    Greenville, South Carolina, 29605

  • Connecticut Children's Medical Center

    Hartford, Connecticut, 06106

  • Memorial Regional Hospital/Joe DiMaggio Children's Hospital

    Hollywood, Florida, 33021

  • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

    Houston, Texas, 77030

  • UT MD Anderson Cancer Center

    Houston, Texas, 77030

  • Riley Hospital for Children

    Indianapolis, Indiana, 46202

  • Ascension Saint Vincent Indianapolis Hospital

    Indianapolis, Indiana, 46260

  • University of Iowa/Holden Comprehensive Cancer Center

    Iowa City, Iowa, 52242

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • Nemours Children's Clinic-Jacksonville

    Jacksonville, Florida, 32207

  • Children's Mercy Hospitals and Clinics

    Kansas City, Missouri, 64108

  • East Tennessee Childrens Hospital

    Knoxville, Tennessee, 37916

  • Arkansas Children's Hospital

    Little Rock, Arkansas, 72202-3591

  • Loma Linda University Medical Center

    Loma Linda, California, 92354

  • Children's Hospital Los Angeles

    Los Angeles, California, 90027

  • Norton Children's Hospital

    Louisville, Kentucky, 40202

  • University of Wisconsin Carbone Cancer Center - University Hospital

    Madison, Wisconsin, 53792

  • Children's Hospital of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Children's Hospitals and Clinics of Minnesota - Minneapolis

    Minneapolis, Minnesota, 55404

  • University of Minnesota/Masonic Cancer Center

    Minneapolis, Minnesota, 55455

  • West Virginia University Healthcare

    Morgantown, West Virginia, 26506

  • Morristown Medical Center

    Morristown, New Jersey, 07960

  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital

    New Brunswick, New Jersey, 08903

  • Yale University

    New Haven, Connecticut, 06520

  • The Steven and Alexandra Cohen Children's Medical Center of New York

    New Hyde Park, New York, 11040

  • Children's Hospital New Orleans

    New Orleans, Louisiana, 70118

  • Laura and Isaac Perlmutter Cancer Center at NYU Langone

    New York, New York, 10016

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Children's Hospital of The King's Daughters

    Norfolk, Virginia, 23507

  • Kaiser Permanente-Oakland

    Oakland, California, 94611

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • Children's Hospital and Medical Center of Omaha

    Omaha, Nebraska, 68114

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

  • Children's Hospital of Orange County

    Orange, California, 92868

  • Arnold Palmer Hospital for Children

    Orlando, Florida, 32806

  • Nemours Children's Hospital

    Orlando, Florida, 32827

  • Lucile Packard Children's Hospital Stanford University

    Palo Alto, California, 94304

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Saint Christopher's Hospital for Children

    Philadelphia, Pennsylvania, 19134

  • Children's Hospital of Pittsburgh of UPMC

    Pittsburgh, Pennsylvania, 15224

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • VCU Massey Comprehensive Cancer Center

    Richmond, Virginia, 23298

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

  • Corewell Health Children's

    Royal Oak, Michigan, 48073

  • Primary Children's Hospital

    Salt Lake City, Utah, 84113

  • Children's Hospital of San Antonio

    San Antonio, Texas, 78207

  • University of Texas Health Science Center at San Antonio

    San Antonio, Texas, 78229

  • Maine Children's Cancer Program

    Scarborough, Maine, 04074

  • Seattle Children's Hospital

    Seattle, Washington, 98105

  • Providence Sacred Heart Medical Center and Children's Hospital

    Spokane, Washington, 99204

  • Cardinal Glennon Children's Medical Center

    St Louis, Missouri, 63104

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Johns Hopkins All Children's Hospital

    St. Petersburg, Florida, 33701

  • State University of New York Upstate Medical University

    Syracuse, New York, 13210

  • Madigan Army Medical Center

    Tacoma, Washington, 98431

  • Saint Joseph's Hospital/Children's Hospital-Tampa

    Tampa, Florida, 33607

  • New York Medical College

    Valhalla, New York, 10595

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010

  • Alfred I duPont Hospital for Children

    Wilmington, Delaware, 19803

  • Wake Forest University Health Sciences

    Winston-Salem, North Carolina, 27157

Other trials in United States

Canada10 sites

  • University of Alberta Hospital

    Edmonton, Alberta, T6G 2B7

  • IWK Health Centre

    Halifax, Nova Scotia, B3K 6R8

  • The Montreal Children's Hospital of the MUHC

    Montreal, Quebec, H3H 1P3

  • Centre Hospitalier Universitaire Sainte-Justine

    Montreal, Quebec, H3T 1C5

  • Children's Hospital of Eastern Ontario

    Ottawa, Ontario, K1H 8L1

  • CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)

    Québec, G1V 4G2

  • Centre Hospitalier Universitaire de Sherbrooke-Fleurimont

    Sherbrooke, Quebec, J1H 5N4

  • Hospital for Sick Children

    Toronto, Ontario, M5G 1X8

  • British Columbia Children's Hospital

    Vancouver, British Columbia, V6H 3V4

  • CancerCare Manitoba

    Winnipeg, Manitoba, R3E 0V9

Other trials in Canada

About this study

Official title: A Phase 3 Study of Selumetinib (NSC# 748727) or Selumetinib in Combination With Vinblastine for Non-NF1, Non-TSC Patients With Recurrent or Progressive Low-Grade Gliomas (LGGs) Lacking BRAFV600E or IDH1 Mutations

This phase III trial investigates the best dose of vinblastine in combination with selumetinib and the benefit of adding vinblastine to selumetinib compared to selumetinib alone in treating children and young adults with low-grade glioma (a common type of brain cancer) that has come back after prior treatment (recurrent) or does not respond to therapy (progressive). Selumetinib is a drug that works by blocking a protein that lets tumor cells grow without stopping. Vinblastine blocks cell growth by stopping cell division and may kill cancer cells. Giving selumetinib in combination with vinblastine may work better than selumetinib alone in treating recurrent or progressive low-grade glioma.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the maximum tolerated dose/recommended phase 2 dose (MTD/RP2D) of selumetinib sulfate (selumetinib) + vinblastine sulfate (vinblastine) for children with progressive or recurrent low-grade gliomas (LGGs).

II. To determine if selumetinib + vinblastine will lead to improved event-free survival (EFS) outcome compared with selumetinib alone for children with progressive or recurrent LGGs.

SECONDARY OBJECTIVES:

  1. To estimate the objective response rates and overall survival associated with treatment with selumetinib + vinblastine versus single-agent selumetinib.

II. To estimate the difference in EFS and response rate between patients with BRAF rearranged LGG and patients with non-BRAF rearranged LGG after treatment with selumetinib + vinblastine versus single-agent selumetinib.

III. To evaluate toxicities associated with selumetinib + vinblastine and single-agent selumetinib for children with progressive or recurrent LGGs.

IV. To compare the quality of life among patients treated with selumetinib + vinblastine and single-agent selumetinib.

  1. To examine the vision outcomes among patients with optic pathway gliomas (OPGs) treated with selumetinib + vinblastine and single-agent selumetinib.

EXPLORATORY OBJECTIVE:

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

OUTLINE: This is a dose-escalation feasibility study of vinblastine sulfate in combination with selumetinib, followed by a randomized efficacy study. Patients in the feasibility study are assigned to Arm I, while patients in the efficacy study are randomized to Arm I or Arm II.

ARM I: Patients receive vinblastine sulfate intravenously (IV) on days 1, 8, 15, and 22 and selumetinib sulfate orally (PO) twice daily (BID) on days 1-28. Treatment repeats every 28 days. Patients receive selumetinib and vinblastine for a total duration of 17 cycles followed by 10 additional cycles of selumetinib alone in the absence of disease progression or unacceptable toxicity. Patients undergo magnetic resonance imaging (MRI) throughout the trial. Patients also undergo blood sample collection during screening and on study.

ARM II: 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 undergo MRI throughout the trial. Patients also undergo blood sample collection during screening and on study.

After completion of study treatment, patients are followed up every 3 months for year 1, every 6 months for years 2-3, and annually for years 4-5.

Being tested
Biospecimen Collection, Magnetic Resonance Imaging, Quality-of-Life Assessment, Questionnaire Administration, Selumetinib Sulfate

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo blood sample collection

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

  • Questionnaire AdministrationOther

    Ancillary studies

  • Selumetinib SulfateDrug

    Also called AZD-6244 Hydrogen Sulfate, AZD6244 Hydrogen Sulfate, AZD6244 Hydrogen Sulphate, Koselugo

    Given PO

  • Vinblastine SulfateDrug

    Also called 29060 LE, 29060-LE, Exal, Velban

    Given IV

Study groups in NCT04576117
Study groupRoleWhat they receive
Efficacy Phase Arm II (selumetinib)Active comparatorPatients 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 undergo MRI throughout the trial. Patients also undergo blood sample collection during screening and on study.
Receives: Procedure: Biospecimen Collection; Procedure: Magnetic Resonance Imaging; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: Selumetinib Sulfate
Feasibility & Efficacy Phase Arm I (selumetinib, vinblastine)ExperimentalPatients receive vinblastine sulfate IV on days 1, 8, 15, and 22 and selumetinib sulfate PO BID on days 1-28. Treatment repeats every 28 days. Patients receive selumetinib and vinblastine for a total duration of 17 cycles followed by 10 additional cycles of selumetinib alone in the absence of disease progression or unacceptable toxicity. Patients undergo MRI throughout the trial. Patients also undergo blood sample collection during screening and on study.
Receives: Procedure: Biospecimen Collection; Procedure: Magnetic Resonance Imaging; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: Selumetinib Sulfate; Drug: Vinblastine Sulfate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum tolerated dose/recommended phase II dose (MTD/RP2D) of selumetinib and vinblastine combination (feasibility)

    The MTD is empirically defined as the highest dose level at which 6 patients have been treated with at most one patient experiencing a dose-limiting toxicity and the next higher dose level has been determined to be too toxic.

    Measured: 1 month post enrollment

  2. Event-free survival (EFS) (efficacy)

    Will use Kaplan-Meier (KM) methods and stratified log-rank tests to estimate EFS per arm and compare the EFS outcome between the two arms to assess difference in efficacy. EFS is defined as the interval from randomization to the first occurrence of clinical or radiographic disease progression, disease recurrence, subsequent malignant neoplasm, or death from any cause. Patients who are event-free will be censored at the time of last follow-up.

    Measured: Up to 5 years after enrollment

Secondary outcomes (7)

  1. Radiographic tumor response rate (efficacy)

    Will summarize the radiologic response rates (complete response [CR] or partial response [PR] per arm and test for a difference between the 2 arms using an exact binomial test. PR is defined as greater than or equal to 50% reduction in target lesion size by bi-dimensional measurement on T2/FLAIR, as compared with the baseline measurements, on a stable or decreasing dose of corticosteroids, accompanied by a stable or improving neurologic examination, and maintained for at least 8 weeks. CR must also be sustained for at least 8 weeks and requires complete disappearance of the target lesion on T2/FLAIR imaging (if enhancement had been present, it must have resolved completely); No new lesions, no new T2/FLAIR abnormalities, and no new or increased enhancement; Patients must be off corticosteroids or only on physiological replacement doses; and Patients should be stable or improved clinically.

    Measured: Up to 2 years after enrollment

  2. Overall survival (OS) (efficacy)

    Will use the KM methods to estimate OS for each treatment arm and use stratified log-rank tests to determine whether there is a difference in OS between the 2 arms. OS is defined as the interval from randomization to death from any cause or to the time of last follow-up for patients who are alive at the time of analysis

    Measured: Up to 5 years after enrollment

  3. EFS by BRAF Status

    Will use KM methods to estimate the difference in EFS and between patients with BRAF rearranged low-grade glioma (LGG) and patients with non-BRAF rearranged LGG after treatment with selumetinib + vinblastine versus single-agent selumetinib. EFS is defined as the interval from randomization to the first occurrence of clinical or radiographic disease progression, disease recurrence, subsequent malignant neoplasm, or death from any cause. Patients who are event-free will be censored at the time of last follow-up

    Measured: Up to 5 years after enrollment

  4. Incidence of adverse events (feasibility)

    Toxicities will be summarized by dose level and by attribution to vinblastine versus selumetinib during the feasibility component.

    Measured: Up to 5 years

  5. Incidence of adverse events (efficacy)

    Reported toxicities will be summarized per arm for the efficacy component.

    Measured: Up to 5 years

  6. Quality of life

    Will use 2-sample 2-sided t-tests to compare the change from baseline in the PedsQL™ Generic Module Total Scale Score between the two treatment arms at Cycle 7 Day 1 for both patient and parent-proxy report.

    Measured: Baseline to cycle 7 day 1

  7. Visual outcome comparison

    Will use an exact binomial test to compare the difference in the proportion of subjects in each arm that show improvement in visual acuity per Teller Acuity assessment after 12 months of treatment using a 1-sided test with 10% type 1 error.

    Measured: 12 months after enrollment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Oct 2020
  2. Study start16 Feb 2021
  3. Primary completion30 Dec 2026 (estimated)
  4. Study completion30 Dec 2026 (estimated)

Resources

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
Sequential
Masking
None (open label)
Enrolment
300 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04576117
Sponsor's protocol ID
NCI-2020-07549
Other IDs
NCI-2020-07549, ACNS1931, ACNS1931, U10CA180886
Status last verified
Jun 2026
First submitted
3 Oct 2020
Last updated
2 Jul 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Biospecimen Collection, Magnetic Resonance Imaging and Quality-of-Life Assessment in people with Recurrent Low Grade Astrocytoma and Recurrent WHO Grade 2 Glioma, run by National Cancer Institute (NCI) at 101 sites in 2 countries.

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 44 inclusion and 31 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: under way, not looking for participants, as of the sponsor's last update on 2 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 101 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

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?

This study is still under way. Results are not available in the source record yet.

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?

Maximum tolerated dose/recommended phase II dose (MTD/RP2D) of selumetinib and vinblastine combination (feasibility) (time frame: 1 month post enrollment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04576117.

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 2 Jul 2026.

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