This phase I/II trial tests the safety, side effects, and best dose of selinexor given in combination with standard radiation therapy in treating children and young adults with newly diagnosed diffuse intrinsic pontine glioma (DIPG) or high-grade glioma (HGG) with a genetic change called H3 K27M mutation. It also tests whether combination of selinexor and standard radiation therapy works to shrink tumors in this patient population. Glioma is a type of cancer that occurs in the brain or spine. Glioma is considered high risk (or high-grade) when it is growing and spreading quickly. The term, risk, refers to the chance of the cancer coming back after treatment. DIPG is a subtype of HGG that grows in the pons (a part of the brainstem that controls functions like breathing, swallowing, speaking, and eye movements). This trial has two parts. The only difference in treatment between the two parts is that some subjects treated in Part 1 may receive a different dose of selinexor than the subjects treated in Part 2. In Part 1 (also called the Dose-Finding Phase), investigators want to determine the dose of selinexor that can be given without causing side effects that are too severe. This dose is called the maximum tolerated dose (MTD). In Part 2 (also called the Efficacy Phase), investigators want to find out how effective the MTD of selinexor is against HGG or DIPG. Selinexor blocks a protein called CRM1, which may help keep cancer cells from growing and may kill them. It is a type of small molecule inhibitor called selective inhibitors of nuclear export (SINE). Radiation therapy uses high energy to kill tumor cells and shrink tumors. The combination of selinexor and radiation therapy may be effective in treating patients with newly-diagnosed DIPG and H3 K27M-Mutant HGG.
PRE ENROLLMENT: Patients must be =< 25 years of age at the time of enrollment on APEC14B1 part A central nervous system (CNS)/high grade glioma (HGG) pre-enrollment eligibility screening
This required age range applies to pre-enrollment eligibility for all HGG patients. Individual treatment protocols may have different age criteria.
Non-DIPG patients with tumors that do not harbor an H3K27M-mutation and are >= 18 years of age will not be eligible to enroll on ACNS1821 (Step 1).
PRE ENROLLMENT: Patient is suspected of having localized, newly diagnosed HGG, excluding metastatic disease, OR patient has an institutional diagnosis of DIPG
STEP 1: Patients must not have received any prior therapy for their central nervous system (CNS) malignancy except for surgery and steroid medications.
STEP 1: Patients who are currently receiving another investigational drug are not eligible.
STEP 1: Patients who are currently receiving other anti-cancer agents are not eligible.
STEP 1: Patients >=18 years of age who have H3 K27M-wild type HGG.
Single group
Biopsy Procedure
Procedure/SurgeryUndergo a biopsy
Magnetic Resonance Imaging
Procedure/SurgeryUndergo a MRI
Radiation Therapy
RadiationUndergo radiation therapy
Selinexor
DrugGiven orally
Maximum tolerated dose
Defined as the highest dose of selinexor in combination with standard of care radiation therapy that does not cause unacceptable side effects.
Event free survival (EFS)
Will be calculated for diffuse midline glioma/ high grade glioma patients. EFS curve will be estimated by Kaplan Meier estimates.
Overall Survival (OS)
Will be calculated for diffuse intrinsic pontine glioma patients. The OS curve will be estimated by Kaplan Meier estimates.
Overall response rate
Defined as the proportion of patients whose best response is partial response or complete response.
Click on the lead sponsor to view all of their trials.