A Study of the Drug Selinexor With Radiation Therapy in Patients With Newly-Diagnosed Diffuse Intrinsic Pontine (DIPG) Glioma and High-Grade Glioma (HGG)
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)
3 other identifiers
interventional
132
4 countries
127
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started May 2022
Longer than P75 for phase_1
127 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 28, 2021
CompletedFirst Posted
Study publicly available on registry
October 29, 2021
CompletedStudy Start
First participant enrolled
May 31, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 30, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 30, 2027
June 12, 2026
January 1, 2026
5.1 years
October 28, 2021
June 11, 2026
Conditions
Outcome Measures
Primary Outcomes (4)
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 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 (DIPG) patients. The OS curve will be estimated by Kaplan Meier estimates.
From the date of enrollment 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
Study Arms (1)
Treatment (selinexor and radiation therapy)
EXPERIMENTALCHEMORADIOTHERAPY: 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.
Interventions
Undergo a biopsy
Undergo a MRI
Undergo radiation therapy
Given orally
Eligibility Criteria
You may qualify if:
- 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:
- 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
- Please note: there are specific radiographic criteria for DIPG patient enrollment on ACNS1821 (Step 1)
- As of February 14, 2025, stratum DIPG and stratum DMG have closed to accrual, and no patients will be enrolled on these strata after Amendment #4.
- PRE ENROLLMENT:
- For patients with non-pontine tumors: Patients and/or their parents or legal guardians must have signed informed consent for eligibility screening on APEC14B1 Part A.
- For patients with DIPG: Patients and/or their parents or legal guardians must have signed informed consent for ACNS1821.
- Note: As of February 14, 2025, stratum DIPG and stratum DMG have closed to accrual, and no patients will be enrolled on these strata after Amendment #4.
- PRE ENROLLMENT:
- For patients with non-pontine tumors only, the specimens obtained at the time of diagnostic biopsy or surgery must be submitted through APEC14B1 ASAP, preferably within 5 calendar days of definitive surgery
- STEP 1: Patients must be \>= 12 months and =\< 21 years of age at the time of enrollment
- STEP 1: Patients must have newly-diagnosed DIPG or HGG (including DMG).
- +34 more criteria
You may not qualify if:
- 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.
- STEP 1: Patients who have an uncontrolled infection.
- STEP 1: Patients who have received a prior solid organ transplantation.
- STEP 1: Patients with grade \> 1 extrapyramidal movement disorder.
- STEP 1: Patients with known macular degeneration, uncontrolled glaucoma, or cataracts.
- STEP 1: Patients with metastatic disease are not eligible; MRI of spine with and without contrast must be performed if metastatic disease is suspected by the treating physician.
- STEP 1: Patients with gliomatosis cerebri type 1 or 2 are not eligible, with the exception of H3 K27M-mutant bithalamic tumors.
- STEP 1: Patients who are not able to receive protocol specified radiation therapy.
- STEP 1:
- Female patients who are pregnant are ineligible since there is yet no available information regarding human fetal or teratogenic toxicities.
- Lactating females are not eligible unless they have agreed not to breastfeed their infants. It is not known whether selinexor is excreted in human milk.
- Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained.
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (127)
Children's Hospital of Alabama
Birmingham, Alabama, 35233, United States
Banner Children's at Desert
Mesa, Arizona, 85202, United States
Phoenix Childrens Hospital
Phoenix, Arizona, 85016, United States
Arkansas Children's Hospital
Little Rock, Arkansas, 72202-3591, United States
Loma Linda University Medical Center
Loma Linda, California, 92354, United States
Miller Children's and Women's Hospital Long Beach
Long Beach, California, 90806, United States
Children's Hospital Los Angeles
Los Angeles, California, 90027, United States
Cedars-Sinai Medical Center
Los Angeles, California, 90048, United States
UCSF Benioff Children's Hospital Oakland
Oakland, California, 94609, United States
Kaiser Permanente-Oakland
Oakland, California, 94611, United States
Children's Hospital of Orange County
Orange, California, 92868, United States
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, 94304, United States
Rady Children's Hospital - San Diego
San Diego, California, 92123, United States
UCSF Medical Center-Mission Bay
San Francisco, California, 94158, United States
Children's Hospital Colorado
Aurora, Colorado, 80045, United States
Connecticut Children's Medical Center
Hartford, Connecticut, 06106, United States
Yale University
New Haven, Connecticut, 06520, United States
Alfred I duPont Hospital for Children
Wilmington, Delaware, 19803, United States
Children's National Medical Center
Washington D.C., District of Columbia, 20010, United States
Golisano Children's Hospital of Southwest Florida
Fort Myers, Florida, 33908, United States
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, 32207, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136, United States
Miami Cancer Institute
Miami, Florida, 33176, United States
Arnold Palmer Hospital for Children
Orlando, Florida, 32806, United States
Nemours Children's Hospital
Orlando, Florida, 32827, United States
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, 33701, United States
Saint Joseph's Hospital/Children's Hospital-Tampa
Tampa, Florida, 33607, United States
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta, Georgia, 30329, United States
Kapiolani Medical Center for Women and Children
Honolulu, Hawaii, 96826, United States
Saint Luke's Cancer Institute - Boise
Boise, Idaho, 83712, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637, United States
OSF Children's Hospital of Illinois
Peoria, Illinois, 61637, United States
Riley Hospital for Children
Indianapolis, Indiana, 46202, United States
Blank Children's Hospital
Des Moines, Iowa, 50309, United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536, United States
Norton Children's Hospital
Louisville, Kentucky, 40202, United States
Children's Hospital New Orleans
New Orleans, Louisiana, 70118, United States
Eastern Maine Medical Center
Bangor, Maine, 04401, United States
Maine Children's Cancer Program
Scarborough, Maine, 04074, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109, United States
Children's Hospital of Michigan
Detroit, Michigan, 48201, United States
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
Grand Rapids, Michigan, 49503, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, 55404, United States
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, 55455, United States
University of Mississippi Medical Center
Jackson, Mississippi, 39216, United States
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108, United States
Cardinal Glennon Children's Medical Center
St Louis, Missouri, 63104, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Mercy Hospital Saint Louis
St Louis, Missouri, 63141, United States
Children's Hospital and Medical Center of Omaha
Omaha, Nebraska, 68114, United States
University of Nebraska Medical Center
Omaha, Nebraska, 68198, United States
Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
Morristown Medical Center
Morristown, New Jersey, 07960, United States
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
New Brunswick, New Jersey, 08903, United States
Newark Beth Israel Medical Center
Newark, New Jersey, 07112, United States
Saint Joseph's Regional Medical Center
Paterson, New Jersey, 07503, United States
Albany Medical Center
Albany, New York, 12208, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
The Steven and Alexandra Cohen Children's Medical Center of New York
New Hyde Park, New York, 11040, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
State University of New York Upstate Medical University
Syracuse, New York, 13210, United States
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467, United States
Novant Health Presbyterian Medical Center
Charlotte, North Carolina, 28204, United States
East Carolina University
Greenville, North Carolina, 27834, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157, United States
Sanford Broadway Medical Center
Fargo, North Dakota, 58122, United States
Children's Hospital Medical Center of Akron
Akron, Ohio, 44308, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229, United States
Rainbow Babies and Childrens Hospital
Cleveland, Ohio, 44106, United States
Nationwide Children's Hospital
Columbus, Ohio, 43205, United States
Dayton Children's Hospital
Dayton, Ohio, 45404, United States
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
Toledo, Ohio, 43606, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
Legacy Emanuel Children's Hospital
Portland, Oregon, 97227, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
Geisinger Medical Center
Danville, Pennsylvania, 17822, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Saint Christopher's Hospital for Children
Philadelphia, Pennsylvania, 19134, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224, United States
Rhode Island Hospital
Providence, Rhode Island, 02903, United States
Prisma Health Richland Hospital
Columbia, South Carolina, 29203, United States
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, 29605, United States
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, 57117-5134, United States
East Tennessee Childrens Hospital
Knoxville, Tennessee, 37916, United States
Saint Jude Children's Research Hospital
Memphis, Tennessee, 38105, United States
The Children's Hospital at TriStar Centennial
Nashville, Tennessee, 37203, United States
Dell Children's Medical Center of Central Texas
Austin, Texas, 78723, United States
Driscoll Children's Hospital
Corpus Christi, Texas, 78411, United States
Medical City Dallas Hospital
Dallas, Texas, 75230, United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390, United States
El Paso Children's Hospital
El Paso, Texas, 79905, United States
Cook Children's Medical Center
Fort Worth, Texas, 76104, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030, United States
M D Anderson Cancer Center
Houston, Texas, 77030, United States
Children's Hospital of San Antonio
San Antonio, Texas, 78207, United States
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229, United States
Primary Children's Hospital
Salt Lake City, Utah, 84113, United States
University of Virginia Cancer Center
Charlottesville, Virginia, 22908, United States
Children's Hospital of The King's Daughters
Norfolk, Virginia, 23507, United States
Seattle Children's Hospital
Seattle, Washington, 98105, United States
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington, 99204, United States
Mary Bridge Children's Hospital and Health Center
Tacoma, Washington, 98405, United States
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792, United States
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Sydney Children's Hospital
Randwick, New South Wales, 2031, Australia
The Children's Hospital at Westmead
Westmead, New South Wales, 2145, Australia
Queensland Children's Hospital
South Brisbane, Queensland, 4101, Australia
Royal Children's Hospital
Parkville, Victoria, 3052, Australia
Perth Children's Hospital
Perth, Western Australia, 6009, Australia
University of Alberta Hospital
Edmonton, Alberta, T6G 2B7, Canada
British Columbia Children's Hospital
Vancouver, British Columbia, V6H 3V4, Canada
CancerCare Manitoba
Winnipeg, Manitoba, R3E 0V9, Canada
IWK Health Centre
Halifax, Nova Scotia, B3K 6R8, Canada
McMaster Children's Hospital at Hamilton Health Sciences
Hamilton, Ontario, L8N 3Z5, Canada
Hospital for Sick Children
Toronto, Ontario, M5G 1X8, Canada
The Montreal Children's Hospital of the MUHC
Montreal, Quebec, H3H 1P3, Canada
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, H3T 1C5, Canada
Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
Sherbrooke, Quebec, J1H 5N4, Canada
Jim Pattison Children's Hospital
Saskatoon, Saskatchewan, S7N 0W8, Canada
CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
Québec, G1V 4G2, Canada
Starship Children's Hospital
Grafton, Auckland, 1145, New Zealand
Christchurch Hospital
Christchurch, 8011, New Zealand
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Adam L Green
Children's Oncology Group
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 28, 2021
First Posted
October 29, 2021
Study Start
May 31, 2022
Primary Completion (Estimated)
June 30, 2027
Study Completion (Estimated)
June 30, 2027
Last Updated
June 12, 2026
Record last verified: 2026-01
Data Sharing
- IPD Sharing
- Will share
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