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Search / Trial NCT04166409

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

Launched by NATIONAL CANCER INSTITUTE (NCI) · Nov 15, 2019

Trial Information

Current as of July 23, 2025

Recruiting

Keywords

ClinConnect Summary

This clinical trial is studying two different treatments for patients with low-grade glioma, a type of brain tumor. The trial compares a new drug called selumetinib, which may help kill tumor cells by blocking certain enzymes, to the standard treatment of carboplatin and vincristine, which are chemotherapy drugs that work in different ways to stop tumor growth. The goal is to find out if selumetinib is just as effective as the standard treatment and whether it can improve the quality of life for patients.

To participate in this trial, patients should be between 2 and 21 years old and must have a specific type of low-grade glioma that does not have a particular genetic mutation (BRAFV600E) or is not associated with a condition called neurofibromatosis type 1. Participants should not have received any prior treatments for their tumor, other than surgery, and need to have measurable tumor size. Throughout the trial, participants will receive regular check-ups and evaluations to monitor their health and the effects of the treatment. It's important to know that there are specific health criteria to meet, and certain medical conditions may exclude someone from joining the study.

Gender

ALL

Eligibility criteria

  • Inclusion Criteria:
  • Patients must be \>= 2 years and =\< 21 years at the time of enrollment
  • Patients must have a body surface area (BSA) of \>= 0.5 m\^2 at enrollment
  • Patients must have non-neurofibromatosis type 1 (non-NF1) low-grade glioma (LGG) without a BRAFV600E mutation as confirmed by Rapid Central Pathology and Molecular Screening Reviews performed on APEC14B1 (NCT02402244) Childhood Cancer Data Initiative (CCDI)-MCI, or accepted Clinical Laboratory Improvement Amendments (CLIA)-certified test and that has not been treated with any modality besides surgery. Note: Patients may be newly-diagnosed OR previously diagnosed, and there is no required time frame between biopsy/surgery and treatment initiation.
  • Patients with residual tumor after resection or progressive tumor after initial diagnosis (with or without surgery) who have not received treatment (chemotherapy and/or radiation) are eligible
  • Patients must have two-dimensional measurable tumor \>= 1 cm\^2 to be eligible
  • Patients with ependymoma are not eligible
  • Eligible histologies will include all tumors considered low-grade glioma or low-grade astrocytoma (World Health Organization \[WHO\] grade I and II) by 5th edition WHO classification of central nervous system (CNS) tumors with the exception of subependymal giant cell astrocytoma
  • Patients with metastatic disease or multiple independent primary LGG are eligible
  • * 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 (performed within 7 days prior to enrollment):
  • Age: Maximum Serum Creatinine (mg/dL)
  • 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 (performed 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 (performed within 7 days prior to enrollment). For the purpose of this study, the ULN for SGPT is 45 U/L
  • Albumin \>= 2 g/dL (performed 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 (performed within 4 weeks prior to enrollment)
  • Corrected QT (QTc) interval =\< 450 msec by electrocardiography (EKG) (performed within 4 weeks prior to enrollment)
  • Absolute neutrophil count \>= 1,000/uL (unsupported) (performed within 7 days prior to enrollment)
  • Platelets \>= 100,000/uL (unsupported) (performed within 7 days prior to enrollment)
  • Hemoglobin \>= 8 g/dL (may be supported) (performed within 7 days prior to enrollment)
  • Patients with a known seizure disorder must be stable and must not have experienced a significant increase in seizure frequency within 2 weeks prior to enrollment
  • 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 8 weeks prior to enrollment
  • For all patients, a magnetic resonance imaging (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 8 weeks prior to enrollment
  • 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
  • All patients have signed an appropriate consent form and Health Insurance Portability and Accountability Act (HIPAA) authorization form (if applicable)
  • All patients and/or their parents or legal guardians must sign a written informed consent
  • All patients have been consented and enrolled on APEC14B1 (NCT02402244) followed by enrollment on the ACNS1833 Pre-Enrollment Eligibility Screening (Step 0) on the same day to complete the Rapid Central Review
  • All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
  • Exclusion Criteria:
  • Patients must not have received any prior tumor-directed therapy including chemotherapy, radiation therapy, immunotherapy, or bone marrow transplant. Prior surgical intervention (with the exclusion of laser interstitial thermal therapy \[LITT\]) is permitted
  • 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
  • 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
  • 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 are not eligible
  • 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
  • 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 Health Association (NYHA) class II-IV prior or current cardiomyopathy
  • Severe valvular heart disease
  • History of atrial fibrillation
  • 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 ULN adjusted by age are not eligible
  • Supplementation with vitamin E greater than 100% of the daily recommended dose. Any multivitamin containing vitamin E must be stopped prior to study enrollment even if less than 100% of the daily recommended dosing for vitamin E
  • Surgery within 2 weeks prior to enrollment, with the exception of surgical biopsy, placement of a vascular access device or cerebral spinal 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

About National Cancer Institute (Nci)

The National Cancer Institute (NCI) is a prominent component of the National Institutes of Health (NIH), dedicated to advancing cancer research and improving patient outcomes through innovative clinical trials. As a leading sponsor of cancer-related studies, NCI focuses on facilitating the development of new therapies, enhancing prevention strategies, and understanding the biology of cancer. The institute collaborates with academic institutions, healthcare providers, and industry partners to conduct rigorous clinical trials that aim to translate scientific discoveries into effective treatments. NCI’s commitment to fostering a robust research environment supports the mission to eliminate cancer as a major health problem.

Locations

New Haven, Connecticut, United States

Durham, North Carolina, United States

Charleston, South Carolina, United States

Philadelphia, Pennsylvania, United States

New York, New York, United States

Buffalo, New York, United States

Saint Louis, Missouri, United States

Detroit, Michigan, United States

Providence, Rhode Island, United States

Boston, Massachusetts, United States

Loma Linda, California, United States

Valhalla, New York, United States

Bangor, Maine, United States

Vancouver, British Columbia, Canada

Peoria, Illinois, United States

Oklahoma City, Oklahoma, United States

Orange, California, United States

Scarborough, Maine, United States

Akron, Ohio, United States

Lubbock, Texas, United States

Norfolk, Virginia, United States

New York, New York, United States

Little Rock, Arkansas, United States

Des Moines, Iowa, United States

Halifax, Nova Scotia, Canada

Jackson, Mississippi, United States

Minneapolis, Minnesota, United States

Austin, Texas, United States

Quebec, , Canada

Hershey, Pennsylvania, United States

Houston, Texas, United States

Tacoma, Washington, United States

San Antonio, Texas, United States

Springfield, Illinois, United States

Cincinnati, Ohio, United States

San Antonio, Texas, United States

Boston, Massachusetts, United States

Los Angeles, California, United States

Rochester, New York, United States

Danville, Pennsylvania, United States

Orlando, Florida, United States

Chicago, Illinois, United States

Chicago, Illinois, United States

Iowa City, Iowa, United States

Baltimore, Maryland, United States

Bethesda, Maryland, United States

Minneapolis, Minnesota, United States

Omaha, Nebraska, United States

New York, New York, United States

Syracuse, New York, United States

Chapel Hill, North Carolina, United States

Winston Salem, North Carolina, United States

Fargo, North Dakota, United States

Nashville, Tennessee, United States

Burlington, Vermont, United States

Birmingham, Alabama, United States

Hartford, Connecticut, United States

Indianapolis, Indiana, United States

Lexington, Kentucky, United States

Charlotte, North Carolina, United States

Morgantown, West Virginia, United States

Washington, District Of Columbia, United States

Honolulu, Hawaii, United States

Portland, Oregon, United States

Pensacola, Florida, United States

Grand Rapids, Michigan, United States

Cleveland, Ohio, United States

Phoenix, Arizona, United States

Oakland, California, United States

San Diego, California, United States

Aurora, Colorado, United States

Wilmington, Delaware, United States

Hollywood, Florida, United States

Jacksonville, Florida, United States

Miami, Florida, United States

Miami, Florida, United States

Tampa, Florida, United States

Chicago, Illinois, United States

New Orleans, Louisiana, United States

Ann Arbor, Michigan, United States

Saint Louis, Missouri, United States

Albany, New York, United States

New Hyde Park, New York, United States

Columbus, Ohio, United States

Dayton, Ohio, United States

Philadelphia, Pennsylvania, United States

Pittsburgh, Pennsylvania, United States

Knoxville, Tennessee, United States

Dallas, Texas, United States

Fort Worth, Texas, United States

Houston, Texas, United States

Salt Lake City, Utah, United States

Richmond, Virginia, United States

Seattle, Washington, United States

Spokane, Washington, United States

Tacoma, Washington, United States

Saint John's, Newfoundland And Labrador, Canada

Montreal, Quebec, Canada

Long Beach, California, United States

Palo Alto, California, United States

San Francisco, California, United States

Fort Myers, Florida, United States

Gainesville, Florida, United States

Orlando, Florida, United States

Orlando, Florida, United States

Saint Petersburg, Florida, United States

Atlanta, Georgia, United States

Indianapolis, Indiana, United States

Louisville, Kentucky, United States

Rochester, Minnesota, United States

Kansas City, Missouri, United States

Omaha, Nebraska, United States

Morristown, New Jersey, United States

Mineola, New York, United States

Columbia, South Carolina, United States

Greenville, South Carolina, United States

Memphis, Tennessee, United States

Roanoke, Virginia, United States

Madison, Wisconsin, United States

Milwaukee, Wisconsin, United States

Montreal, Quebec, Canada

Los Angeles, California, United States

Greenville, North Carolina, United States

Mesa, Arizona, United States

Los Angeles, California, United States

Pensacola, Florida, United States

Boise, Idaho, United States

Royal Oak, Michigan, United States

Sherbrooke, Quebec, Canada

San Antonio, Texas, United States

Lubbock, Texas, United States

El Paso, Texas, United States

Caguas, , Puerto Rico

Philadelphia, Pennsylvania, United States

Mineola, New York, United States

Indianapolis, Indiana, United States

Quebec, , Canada

Madison, Wisconsin, United States

Grand Rapids, Michigan, United States

Royal Oak, Michigan, United States

Atlanta, Georgia, United States

Patients applied

0 patients applied

Trial Officials

Peter M de Blank

Principal Investigator

Children's Oncology Group

Timeline

First submit

Trial launched

Trial updated

Estimated completion

Not reported

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