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; Parker, Melanie; Armatti, Julie M; Doyle, Katherine M; Dubberly, Paige D
Trial Phone: 321.841.5357 ; 321-843-1036 ; 321-843-5284 ; 3218412008 ; 321-841-7561
-
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
