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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)

  • Clinical Trial Information

    Trial Contact: Spinelli, Jennifer; Leffin, Melissa; El-Shami, Jessica

  • IRB No: ACNS1833

    Protocol Abbrev: ACNS1833

    Principal Investigator: Amy A Smith, MD

    Phase: Drug: Phase III

    Age Group: Adult;Pediatric

    Secondary Protocol No: ACNS1833

    Treatment: Drug: Carboplatin, Drug: Selumetinib, Drug: Selumetinib Sulfate, Drug: Vincristine, Drug: Vincristine Sulfate

    Therapies Involved: Chemotherapy

    ClinicalTrials.gov ID: NCT04166409

  • Objective

    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).

  • Key Eligibility

    •  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 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:
    ◦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 (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. For the purpose of this study, the ULN for SGPT is 45 U/L
    •  Albumin >= 2 g/dL
    •  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
    •  Corrected QT (QTc) interval =< 450 msec by electrocardiography (EKG)
    •  Absolute neutrophil count >= 1,000/uL (unsupported)
    •  Platelets >= 100,000/uL (unsupported)
    •  Hemoglobin >= 8 g/dL (may be supported)
    •  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)
    •  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