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A Study of the Drug Selinexor With Radiation Therapy in Patients With Newly-Diagnosed Diffuse Intrinsic Pontine (DIPG) Glioma 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.
Study details:
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.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
Exclusion criteria
Eligibility
Age eligible for study : 12 and older
Healthy volunteers accepted : No
Gender eligible for study: All
Things to know
Study dates
Study start: 2022-05-31
Primary completion: 2027-06-30
Study completion finish: 2027-06-30
Study type
TREATMENT
Phase
PHASE1
PHASE2
Trial ID
NCT05099003
Intervention or treatment
PROCEDURE: Biopsy
PROCEDURE: Magnetic Resonance Imaging
RADIATION: Radiation Therapy
DRUG: Selinexor
Conditions
- • Anaplastic Astrocytoma
- • Diffuse Intrinsic Pontine Glioma
- • Diffuse Midline Glioma, H3 K27M-Mutant
- • Glioblastoma
- • Malignant Glioma
- • Anaplastic Astrocytoma, Not Otherwise Specified
- • Glioblastoma, Not Otherwise Specified
Find a site
Closest Location:
Queensland Children's Hospital
Research sites nearby
Select from list below to view details:
Queensland Children's Hospital
South Brisbane, Queensland, Australia
Royal Children's Hospital
Parkville, Victoria, Australia
Perth Children's Hospital
Perth, Western Australia, Australia
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Participant Group/Arm | Intervention/Treatment |
---|---|
EXPERIMENTAL: Treatment (selinexor and radiation therapy)
| PROCEDURE: Biopsy
|
What is the study measuring?
Primary outcome
Primary Outcome Measure | Primary Outcome Description | Primary Outcome Time Frame |
---|---|---|
Maximum tolerated dose | Defined as the highest dose of selinexor in combination with standard of care radiation therapy (RT) that does not cause unacceptable side effects. | 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 (DMG)/ high grade glioma (HGG) patients. EFS curve will be estimated by Kaplan Meier estimates. | From the date of diagnosis 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 (DIPG) patients. The OS curve will be estimated by Kaplan Meier estimates. | From the date of diagnosis until death date of any cause or last follow-up date, assessed up to 5 years |
Overall response rate (ORR) | Defined as the proportion of patients whose best response is partial response or complete response. | Up to 5 years |
Secondary outcome
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