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

Inclusion Criteria

• •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
• •* 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