Title
A Phase 3 Randomized Study of Selumetinib (IND # 77782) versus Carboplatin/Vincristine in Newly Diagnosed or Previously Untreated Neurofibromatosis Type 1 (NF1) Associated Low-Grade Glioma (LGG)

Description
A Phase 3 Randomized Study of Selumetinib versus Carboplatin/Vincristine in Newly Diagnosed or Previously Untreated Neurofibromatosis Type 1 (NF1) associated Low-Grade Glioma (LGG)

Objective
The overall goals of this study are to see if a drug called selumetinib works just as well as the standard treatment using carboplatin and vincristine (called CV) for subjects with NF1-associated LGG, and to see if selumetinib is better than CV in improving vision in subjects with LGG of the optic pathway

Treatment In this study you will get 1 of 2 treatment plans. The 2 treatment plans are called Arm 1 and Arm 2. The treatment on Arm 1 is CV, which is standard therapy for people with NF1-associated LGG. For subjects getting CV, the treatment on this study takes about 15 months. The treatment on Arm 2 is selumetinib, which is an experimental therapy for people with NF1-associated LGG. For subjects getting selumetinib, the treatment on this study takes about 27 months. In addition to the length of the study treatment, all subjects will complete research tests for about 5 years after they enter this study. The treatment plan that you receive is decided by a process called randomization. Randomization means that the treatment is assigned based on chance. It is a lot like flipping a coin, except that it is done by computer. You and your doctor will not pick which treatment you get

Key Eligibility
Must be enrolled before treatment begins. The date protocol therapy is projected to start must be no later than five (5) calendar days after the date of study enrollment

Both men and women of all races and ethnic groups are eligible for this study

Must be greater than or equal to 2 years and less than or equal to 21 years

Must have a body surface area (BSA) of greater than or equal 0.5 m2

Must have Neurofibromatosis Type 1 (NF1) based on clinical criteria and/or germline genetic testing

Must be newly diagnosed or have previously diagnosed NF-1 associated LGG that has not been treated with any modality other than surgery

Patients with optic pathway gliomas (OPGs): Newly-diagnosed patients with OPG are eligible if there are neurologic symptoms (including visual dysfunction) or other exam findings associated with the tumor, Previously-diagnosed patients with OPG are eligible if they have new or worsening neurologic symptoms (including visual dysfunction) or have tumor growth; For both newly-diagnosed and previously-diagnosed OPG, the patient may be eligible, irrespective of whether there has been tumor growth or other neurological symptoms or worsening, if they meet at least one of the following visual criteria: Visual worsening, defined as worsening of visual acuity (VA) or visual fields (VF) documented within the past year (by examination or history); OR Significant visual dysfunction (defined as VA worse than normal for age by 0.6 logMAR or more in one or both eyes)

LGG in other locations (i.e., not OPGs): Newly-diagnosed patients with LGG are eligible if there are neurologic symptoms or other exam findings associated with the tumor. NOTE: Newly-diagnosed patients with LGG without associated neurologic symptoms or exam findings are not eligible. • Previously-diagnosed patients with LGG are eligible if they have new or worsening neurologic symptoms or have tumor growth

Must have two-dimensional measurable tumor greater than or equal to 1cm2

Adequate renal, liver, cardiac, bone marrow and central nervous system function as defined by the protocol

Performance status corresponding to ECOG scores of 0, 1, or 2. Use Karnofsky for patients greater than 16 years of age and Lansky for patients less than or equal to 16 years of age

Must have the ability to swallow whole capsules

EXCLUSION

Must not have received any prior tumor-directed therapy including chemotherapy, radiation therapy, immunotherapy, or bone marrow transplant. Prior surgical intervention is permitted

May not be receiving any other investigational agents

Can not be pregnant or breast feeding

Male and Female of childbearing potential must agree to adequate birth control as defined by the protocol

Pre-existing conditions: Cardiac Conditions and Ophthalmologic Conditions as defined by the protocol

Uncontrolled infection are not eligible

Applicable Disease Sites
Brain/Central Nervous System

Participating Institutions
Gundersen Health System; UW Health University Hospital