A Phase 1/2 interventional study of Biopsy Procedure and Magnetic Resonance Imaging in Malignant Glioma, sponsored by National Cancer Institute (NCI). Recruiting at 127 sites in 4 countries. Open to participants aged 12 Months to 21 Years. Per ClinicalTrials.gov, last updated 2026-09-16.
Sponsored by National Cancer Institute (NCI) · Phase 1/2, Interventional, and Treatment
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.
PRIMARY OBJECTIVES:
I. To define toxicities and estimate the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of selinexor administered as an oral formulation in combination with standard of care radiation therapy (RT), to pediatric patients with newly diagnosed high-grade glioma (HGG) or diffuse intrinsic pontine glioma (DIPG). (Dose-finding phase/phase I) II. To estimate the event-free survival (EFS) distribution for diffuse midline glioma (DMG)/HGG patients and overall survival (OS) distribution for DIPG patients associated with selinexor plus RT, followed by selinexor in patients with newly diagnosed HGG (H3 K27M mutant DMG or H3 K27-wild type HGG) or DIPG, and to compare those outcomes to historical controls. (Efficacy phase/phase II)
EXPLORATORY OBJECTIVE:
I. To bank tumor specimens and body fluids (blood and cerebrospinal fluid) for future studies.
OUTLINE: This is a phase I dose-escalation study of selinexor followed by a phase II study. (STRATUM DIPG AND STRATUM DMG CLOSED TO ACCRUAL 02/14/2025)
CHEMORADIOTHERAPY: Patients receive standard of care radiation therapy 5 days per week for 5-7 weeks. Starting on day 4 or 5 of radiation therapy, patients receive selinexor orally (PO) on days 1, 8, 15, 22, 29, 36, 43, and 50 in the absence of disease progression or unacceptable toxicity. After a 2-week rest period, patients proceed to Maintenance. Patients undergo a magnetic resonance imaging (MRI) and may undergo a biopsy during screening.
MAINTENANCE: Patients receive selinexor PO on days 1, 8, 15, and 22 of each cycle. Cycles repeat every 28 days for up to 24 cycles of maintenance therapy in the absence of disease progression or unacceptable toxicity. Patients undergo a MRI on study and during follow-up.
After completion of study treatment, patients are followed every 3 months for year 1 (i.e., 3, 6, 9, 12 months), then every 6 months for years 2-3 (i.e., 18, 24, 30, 36 months), and finally once yearly for years 4-5 of this study.
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
Please note:
PRE ENROLLMENT: Patient is suspected of having localized, newly diagnosed HGG, excluding metastatic disease, OR patient has an institutional diagnosis of DIPG
PRE ENROLLMENT:
PRE ENROLLMENT:
STEP 1: Stratum DIPG (Closed with Amendment #4)
STEP 1: Stratum DMG (with H3 K27M mutation) (Closed with Amendment #4)
STEP 1: Stratum HGG (without H3 K27M mutation)
Please note:
A serum creatinine based on age/sex as follows (within 7 days prior to step 1 enrollment):
Age / Maximum Serum Creatinine (mg/dL)
>= 16 years / male: 1.7; female: 1.4
For patients who have a biopsy followed by resection, the date of resection will be considered the date of definitive diagnostic surgery. If a biopsy only was performed, the biopsy date will be considered the date of definitive diagnostic surgery.
Exclusion Criteria:
STEP 1:
CHEMORADIOTHERAPY: Patients receive standard of care radiation therapy 5 days per week for 5-7 weeks. Starting on day 4 or 5 of radiation therapy, patients receive selinexor PO on 1, 8, 15, 22, 29, 36, 43, and 50 in the absence of disease progression or unacceptable toxicity. After a 2-week rest period, patients proceed to Maintenance. Patients undergo a MRI and may undergo a biopsy during screening. MAINTENANCE: Patients receive selinexor PO on days 1, 8, 15, and 22 of each cycle. Cycles repeat every 28 days for up to 24 cycles of maintenance therapy in the absence of disease progression or unacceptable toxicity. Patients undergo a MRI on study and during follow-up.
Procedure: Biopsy Procedure · Procedure: Magnetic Resonance Imaging · Radiation: Radiation Therapy · Drug: Selinexor
Undergo a biopsy
Also known as: Biopsy, BIOPSY_TYPE, Bx
Undergo a MRI
Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI
Undergo radiation therapy
Also known as: Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation
Given orally
Also known as: ATG-010, CRM1 Nuclear Export Inhibitor KPT-330, KPT 330, KPT-330, KPT330, Nexpovio, Selective Inhibitor of Nuclear Export KPT-330, SINE KPT-330, Xpovio
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.
Time frame: From day 1 of selinexor treatment until the start of maintenance therapy, assessed up to 10 weeks from treatment start date
Event free survival (EFS)
Will be calculated for diffuse midline glioma/ high grade glioma patients. EFS curve will be estimated by Kaplan Meier estimates.
Time frame: From the date of enrollment until disease progression date, secondary malignant neoplasm occurrence date, death date of any cause, or last follow-up date, assessed up to 5 years
Overall Survival (OS)
Will be calculated for diffuse intrinsic pontine glioma patients. The OS curve will be estimated by Kaplan Meier estimates.
Time frame: From the date of enrollment until death date of any cause or last follow-up date, assessed up to 5 years
Overall response rate
Defined as the proportion of patients whose best response is partial response or complete response.
Time frame: Up to 5 years
Showing the first 100 of 127 sites across 4 countries.
Plan to share: Yes — NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page
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