A Study of the Drugs Selumetinib vs. Carboplatin and Vincristine in Patients With Low-Grade Glioma
Low Grade Astrocytoma, Low Grade Glioma, Metastatic Low Grade Astrocytoma
About this trial
This is an interventional treatment trial for Low Grade Astrocytoma
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) 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
- 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/gender 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 should be stable and should 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 gender at the time of enrollment (with or without the use of anti-hypertensive medications)
- All patients must have ophthalmology toxicity assessments performed within 4 weeks prior to enrollment
- 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
- 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 4 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 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
Sites / Locations
- Children's Hospital of AlabamaRecruiting
- Banner Children's at DesertRecruiting
- Phoenix Childrens HospitalRecruiting
- Arkansas Children's HospitalRecruiting
- Loma Linda University Medical CenterRecruiting
- Children's Hospital Los AngelesRecruiting
- Cedars Sinai Medical CenterRecruiting
- Mattel Children's Hospital UCLARecruiting
- Kaiser Permanente-OaklandRecruiting
- Children's Hospital of Orange CountyRecruiting
- Lucile Packard Children's Hospital Stanford UniversityRecruiting
- Rady Children's Hospital - San DiegoRecruiting
- UCSF Medical Center-Mission BayRecruiting
- Children's Hospital ColoradoRecruiting
- Connecticut Children's Medical CenterRecruiting
- Yale UniversityRecruiting
- Alfred I duPont Hospital for ChildrenRecruiting
- Children's National Medical CenterRecruiting
- University of Florida Health Science Center - GainesvilleRecruiting
- Memorial Regional Hospital/Joe DiMaggio Children's HospitalRecruiting
- Nemours Children's Clinic-JacksonvilleRecruiting
- University of Miami Miller School of Medicine-Sylvester Cancer Center
- Nicklaus Children's HospitalRecruiting
- AdventHealth OrlandoRecruiting
- Arnold Palmer Hospital for ChildrenRecruiting
- Nemours Children's HospitalRecruiting
- Sacred Heart HospitalRecruiting
- Johns Hopkins All Children's HospitalRecruiting
- Children's Healthcare of Atlanta - EglestonRecruiting
- Kapiolani Medical Center for Women and ChildrenRecruiting
- Saint Luke's Cancer Institute - BoiseRecruiting
- Lurie Children's Hospital-ChicagoRecruiting
- University of IllinoisRecruiting
- University of Chicago Comprehensive Cancer CenterRecruiting
- Southern Illinois University School of MedicineRecruiting
- Riley Hospital for ChildrenRecruiting
- Ascension Saint Vincent Indianapolis HospitalRecruiting
- Blank Children's HospitalRecruiting
- University of Iowa/Holden Comprehensive Cancer CenterRecruiting
- University of Kentucky/Markey Cancer CenterRecruiting
- Norton Children's HospitalRecruiting
- Children's Hospital New OrleansRecruiting
- Eastern Maine Medical CenterRecruiting
- Maine Children's Cancer ProgramRecruiting
- Johns Hopkins University/Sidney Kimmel Cancer CenterRecruiting
- Walter Reed National Military Medical CenterRecruiting
- Massachusetts General Hospital Cancer CenterRecruiting
- Dana-Farber Cancer InstituteRecruiting
- C S Mott Children's HospitalRecruiting
- Children's Hospital of MichiganRecruiting
- Helen DeVos Children's Hospital at Spectrum HealthRecruiting
- Beaumont Children's Hospital-Royal OakRecruiting
- Children's Hospitals and Clinics of Minnesota - MinneapolisRecruiting
- University of Minnesota/Masonic Cancer CenterRecruiting
- Mayo Clinic in RochesterRecruiting
- University of Mississippi Medical CenterRecruiting
- Children's Mercy Hospitals and ClinicsRecruiting
- Cardinal Glennon Children's Medical CenterRecruiting
- Washington University School of MedicineRecruiting
- Children's Hospital and Medical Center of OmahaRecruiting
- University of Nebraska Medical CenterRecruiting
- Morristown Medical CenterRecruiting
- Albany Medical CenterRecruiting
- Roswell Park Cancer InstituteRecruiting
- NYU Winthrop HospitalRecruiting
- The Steven and Alexandra Cohen Children's Medical Center of New YorkRecruiting
- Laura and Isaac Perlmutter Cancer Center at NYU LangoneRecruiting
- Memorial Sloan Kettering Cancer CenterRecruiting
- State University of New York Upstate Medical UniversityRecruiting
- New York Medical CollegeRecruiting
- UNC Lineberger Comprehensive Cancer CenterRecruiting
- Carolinas Medical Center/Levine Cancer InstituteRecruiting
- Duke University Medical CenterRecruiting
- East Carolina UniversityRecruiting
- Wake Forest University Health SciencesRecruiting
- Sanford Broadway Medical CenterRecruiting
- Children's Hospital Medical Center of AkronRecruiting
- Cincinnati Children's Hospital Medical CenterRecruiting
- Rainbow Babies and Childrens HospitalRecruiting
- Nationwide Children's HospitalRecruiting
- Dayton Children's HospitalRecruiting
- University of Oklahoma Health Sciences CenterRecruiting
- Oregon Health and Science UniversityRecruiting
- Geisinger Medical CenterRecruiting
- Penn State Children's HospitalRecruiting
- Children's Hospital of PhiladelphiaRecruiting
- Children's Hospital of Pittsburgh of UPMCRecruiting
- Rhode Island HospitalRecruiting
- Medical University of South CarolinaRecruiting
- Prisma Health Richland HospitalRecruiting
- BI-LO Charities Children's Cancer CenterRecruiting
- East Tennessee Childrens HospitalRecruiting
- Saint Jude Children's Research HospitalRecruiting
- Vanderbilt University/Ingram Cancer CenterRecruiting
- Dell Children's Medical Center of Central TexasRecruiting
- UT Southwestern/Simmons Cancer Center-DallasRecruiting
- El Paso Children's HospitalRecruiting
- Cook Children's Medical CenterRecruiting
- Baylor College of Medicine/Dan L Duncan Comprehensive Cancer CenterRecruiting
- M D Anderson Cancer CenterRecruiting
- Covenant Children's HospitalRecruiting
- UMC Cancer Center / UMC Health SystemRecruiting
- Children's Hospital of San AntonioRecruiting
- Methodist Children's Hospital of South TexasRecruiting
- University of Texas Health Science Center at San AntonioRecruiting
- Primary Children's HospitalRecruiting
- University of Vermont and State Agricultural CollegeRecruiting
- Children's Hospital of The King's DaughtersRecruiting
- Virginia Commonwealth University/Massey Cancer CenterRecruiting
- Carilion Children'sRecruiting
- Seattle Children's HospitalRecruiting
- Providence Sacred Heart Medical Center and Children's HospitalRecruiting
- Mary Bridge Children's Hospital and Health CenterRecruiting
- Madigan Army Medical CenterRecruiting
- West Virginia University HealthcareRecruiting
- University of Wisconsin Carbone Cancer CenterRecruiting
- Children's Hospital of WisconsinRecruiting
- IWK Health CentreRecruiting
- The Montreal Children's Hospital of the MUHCRecruiting
- Centre Hospitalier Universitaire Sainte-JustineRecruiting
- CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)Recruiting
- HIMA San Pablo Oncologic HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Active Comparator
Experimental
Arm I (vincristine sulfate, carboplatin)
Arm II (selumetinib sulfate)
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.