A Study of the Drugs Selumetinib vs. Carboplatin and Vincristine in Patients With Low-Grade Glioma
About
A Phase 3 Randomized Non-Inferiority Study of Carboplatin and Vincristine versus Selumetinib (NSC# 748727, IND# 77782) in Newly Diagnosed or Previously Untreated Low-Grade Glioma (LGG) not associated with BRAFV600E Mutations or Systemic Neurofibromatosis Type 1 (NF1)
Low-grade gliomas (LGG) are the most common central nervous system tumors in children. Although surgical resection is the mainstay of therapy, complete resection can be difficult due to tumor location and can lead to adverse effects. This phase III trial compares the effect of selumetinib vs the standard of care treatment with carboplatin and vincristine (CV) in treating patients with newly diagnosed or previously untreated low-grade glioma (LGG). Selumetinib works by blocking some of the enzymes needed for cell growth and may kill tumor cells. Carboplatin and vincristine are chemotherapy drugs that work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. The overall goal of this study is to see if selumetinib works just as well as the standard treatment of CV for patients with LGG.
Study Plan: A goal of this study is to compare the effects of selumetinib vs carboplatin and vincristine (common chemotherapy drugs) in subjects with low-grade gliomas to find out which is better in stopping the growth of cancer cells. This trial will also examine if treatment with selumetinib improves the quality of life for subjects who take it. Patients will be randomized between two groups.
Arm A: vincristine sulfate, carboplatin
Arm B: selumetinib sulfate
COG # ACNS1833
Eligibility Criteria
Inclusion Criteria
- Diagnosis: Patients must have non-neurofibromatosis type 1 (non-NF1) low-grade glioma (LGG) without a BRAFV600E mutation
- No prior treatment besides surgery. Note: Patients may be newly diagnosed OR previously diagnosed, and there is no required timeframe 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 cm2 to be eligible.
- Age
- Patients must be ≥ 2 years and ≤ 21 years at the time of enrollment.
- Body Surface Area
- Patients must have a body surface area (BSA) of ≥ 0.5 m2 at enrollment.
- Adequate renal, liver, cardiac and bone marrow function as defined the by protocol
- Patients with a known seizure disorder should be stable
- Written informed consent must be signed by patient and/or guardians
Exclusion Criteria
- No prior therapy
- 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 may not be receiving any other investigational agents.
- Pregnant or lactating female patients
- Pre-existing cardiac and ophthalmologic conditions as defined by protocol
Primary Investigator
Dr. Glenn Edwards is the section chief of Pediatric Hematology/Oncology, as well as the Children's Oncology Group's principal investigator for Carilion Clinic. With over 30 years of clinical experience, he is board certified by the American Board of Pediatrics in Pediatrics and Pediatric Hematology/Oncology. He completed his fellowship at Walter Reed Army Medical Center and completed his internship and residency at Tripler Army Medical Center.
Contact Information
Wendy McCarty, CCRP
Clinical Research Coordinator
Sydnee Moses, BS
Clinical Research Coordinator
