Glioblastoma Clinical Trial
Official title:
A Phase 1/2 Trial of Selinexor (KPT-330) and Radiation Therapy in Newly-Diagnosed Pediatric Diffuse Intrinsic Pontine Glioma (DIPG) and High-Grade Glioma (HGG)
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. 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. ;
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