New combo therapy hopes to fight deadly childhood brain cancers
NCT ID NCT05099003
First seen Jun 25, 2026 · Last updated Sep 17, 2026 · Updated 34 times
Summary
This trial tests a drug called selinexor combined with standard radiation in children and young adults with newly diagnosed diffuse intrinsic pontine glioma (DIPG) or high-grade glioma (HGG) that has a specific genetic change (H3 K27M mutation). The study has two parts: first, finding the safest dose of selinexor, then seeing how well it works to shrink tumors. About 132 participants will be enrolled.
What this could mean
Our plain-language read of the trial. This is informational only, not medical advice or a prediction.
- Active substance
- selinexor (a drug that blocks a protein called CRM1 to stop cancer cell growth)
- What this could lead to
- If it works, this could point toward a new treatment option for children with these aggressive brain tumors, potentially improving survival.
- What could go wrong
- This is an early-phase trial (phase 1/2) with a small number of participants, so the drug may not work or could cause severe side effects. The tumors are very hard to treat, so success is uncertain.
This is an AI summary of the original study and may miss details. Read our disclaimer.
Study facts
What this study's own registry entry says, in plain language.
- Phase
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Phase 1/2
Runs two stages together: safety and dose first, then whether the treatment works.
- Participants
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About 132 people
The number the study aims to enrol. It can still change while the study runs.
- Started
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May 2022
- Expected to finish
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Jun 2027
An estimate. End dates often move.
- Lead sponsor
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A government research agency
The lead sponsor is the US National Institutes of Health.
Who can take part
This study's own entry requirements. Only the study team can say for certain whether you qualify.
- Ages
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12 months to 21 years
- Sex
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Anyone
- Healthy volunteers
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Not accepted
This study is not open to healthy volunteers. The entry requirements below say who it is open to.
Show the full entry requirements Hide the full entry requirements
Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.
Inclusion Criteria: * 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). * STEP 1: Stratum DIPG (Closed with Amendment #4) * 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. * Patients with newly-diagnosed typical DIPG, defined as tumors with a pontine epicenter and diffuse involvement of at least 2/3 of the pons on at least 1 axial T2 weighted image, are eligible. No histologic confirmation is required. * Patients with pontine tumors that do not meet radiographic criteria for typical DIPG (e.g., focal tumors or those involving less than 2/3 of the pontine cross-sectional area with or without extrapontine extension) are eligible if the tumors are biopsied and proven to be high-grade gliomas (such as anaplastic astrocytoma, glioblastoma, high-grade glioma not otherwise specified \[NOS\], and/or H3 K27M-mutant) by institutional diagnosis. * STEP 1: Stratum DMG (with H3 K27M mutation) (Closed with Amendment #4) * 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. * Patients must have newly-diagnosed non-pontine H3 K27M-mutant HGG without BRAF V600 or IDH1 mutations as confirmed by Rapid Central Pathology and Molecular Screening Reviews performed on APEC14B1 * Note: Patients need not have either measurable or evaluable disease, i.e., DMG patients may have complete resection of their tumor prior to enrollment. Primary spinal tumors are eligible for enrollment. For rare H3 K27M-mutant HGG in non-midline structures (e.g., cerebral hemispheres), these patients will be considered part of Stratum DMG. * STEP 1: Stratum HGG (without H3 K27M mutation) * Patients must have newly-diagnosed non-pontine H3 K27M-wild type HGG without BRAF V600 or IDH1 mutations as confirmed by Rapid Central Pathology and Molecular Screening Reviews performed on APEC14B1 * Please note: * Patients who fall in this category and who are \>= 18 years of age are not eligible due to another standard-of-care regimen (radiation/temozolomide) that is available * Patients need not have either measurable or evaluable disease, i.e., HGG patients may have complete resection of their tumor prior to enrollment. Primary spinal tumors are eligible for enrollment * STEP 1: Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients \> 16 years of age and Lansky for patients =\<16 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score. * STEP 1: Peripheral absolute neutrophil count (ANC) \>= 1000/uL (within 7 days prior to step 1 enrollment) * STEP 1: Platelet count \>= 100,000/uL (transfusion independent) (within 7 days prior to step 1 enrollment) * STEP 1: Hemoglobin \>= 8.0 g/dL (may receive red blood cell \[RBC\] transfusions) (within 7 days prior to step 1 enrollment) * STEP 1: Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 (within 7 days prior to step 1 enrollment) or A serum creatinine based on age/sex as follows (within 7 days prior to step 1 enrollment): * Age / Maximum Serum Creatinine (mg/dL) * 1 to \< 2 years / male: 0.6; female: 0.6 * 2 to \< 6 years / male: 0.8; female: 0.8 * 6 to \< 10 years / male: 1; female: 1 * 10 to \< 13 years / male: 1.2; female: 1.2 * 13 to \< 16 years / male: 1.5; female: 1.4 * \>= 16 years / male: 1.7; female: 1.4 * STEP 1: Total bilirubin =\< 1.5 x upper limit of normal (ULN) for age * STEP 1: Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L. * STEP 1: Serum amylase =\< 1.5 x ULN * STEP 1: Serum lipase =\< 1.5 x ULN * STEP 1: No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry \> 94% if there is clinical indication for determination. * STEP 1: Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled. * STEP 1: Patients must be enrolled and protocol therapy must begin no later than 31 days after the date of radiographic diagnosis (in the case of non-biopsied DIPG patients only) or definitive surgery, whichever is the later date (Day 0). 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: 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. * Sexually active patients of reproductive potential are not eligible unless they have agreed to use two effective methods of birth control (including a medically accepted barrier method of contraception, e.g., male or female condom) for the duration of their study participation and for 90 days after the last dose of selinexor. Abstinence is an acceptable method of birth control.
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Genom att skicka in godkänner du våra Användarvillkor
Conditions
The condition(s) this trial relates to.
As listed by the trial registrant
The condition terms exactly as the trial's registrant entered them.
How to take part
Only the study team decides who joins. These are the ways to reach them.
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The study's own enquiry address
This study publishes an address for enquiries. See it below .
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The places running it
125 sites in 4 countries. The list below names each one and where it is.
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The official record
ClinicalTrials.gov lists the study team's own contact details, including names and phone numbers. We don't republish those.
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A doctor treating you
A doctor who knows your case can contact a study site on your behalf, and can tell you whether this study is worth pursuing at all.
Contacts and locations
Show contact details
Enter your email to view the contact information for this study.
Genom att skicka in godkänner du våra Användarvillkor
Locations
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Albany Medical Center
RECRUITINGAlbany, New York, 12208, United States
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Alfred I duPont Hospital for Children
RECRUITINGWilmington, Delaware, 19803, United States
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Arkansas Children's Hospital
RECRUITINGLittle Rock, Arkansas, 72202-3591, United States
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Arnold Palmer Hospital for Children
RECRUITINGOrlando, Florida, 32806, United States
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BI-LO Charities Children's Cancer Center
RECRUITINGGreenville, South Carolina, 29605, United States
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Banner Children's at Desert
RECRUITINGMesa, Arizona, 85202, United States
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Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
RECRUITINGHouston, Texas, 77030, United States
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Blank Children's Hospital
RECRUITINGDes Moines, Iowa, 50309, United States
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British Columbia Children's Hospital
SUSPENDEDVancouver, British Columbia, V6H 3V4, Canada
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C S Mott Children's Hospital
RECRUITINGAnn Arbor, Michigan, 48109, United States
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CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
RECRUITINGQuébec, G1V 4G2, Canada
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CancerCare Manitoba
RECRUITINGWinnipeg, Manitoba, R3E 0V9, Canada
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Cardinal Glennon Children's Medical Center
RECRUITINGSt Louis, Missouri, 63104, United States
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Cedars-Sinai Medical Center
RECRUITINGLos Angeles, California, 90048, United States
Contact Email: •••••@•••••
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Centre Hospitalier Universitaire Sainte-Justine
RECRUITINGMontreal, Quebec, H3T 1C5, Canada
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Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
RECRUITINGSherbrooke, Quebec, J1H 5N4, Canada
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Children's Healthcare of Atlanta - Arthur M Blank Hospital
RECRUITINGAtlanta, Georgia, 30329, United States
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Children's Hospital Colorado
RECRUITINGAurora, Colorado, 80045, United States
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Children's Hospital Los Angeles
RECRUITINGLos Angeles, California, 90027, United States
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Children's Hospital Medical Center of Akron
RECRUITINGAkron, Ohio, 44308, United States
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Children's Hospital New Orleans
RECRUITINGNew Orleans, Louisiana, 70118, United States
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Children's Hospital and Medical Center of Omaha
RECRUITINGOmaha, Nebraska, 68114, United States
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Children's Hospital of Alabama
RECRUITINGBirmingham, Alabama, 35233, United States
Contact Email: •••••@•••••
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Children's Hospital of Michigan
RECRUITINGDetroit, Michigan, 48201, United States
Contact Email: •••••@•••••
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Children's Hospital of Orange County
RECRUITINGOrange, California, 92868, United States
Contact Email: •••••@•••••
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Children's Hospital of Philadelphia
RECRUITINGPhiladelphia, Pennsylvania, 19104, United States
Contact Email: •••••@•••••
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Children's Hospital of Pittsburgh of UPMC
RECRUITINGPittsburgh, Pennsylvania, 15224, United States
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Children's Hospital of San Antonio
RECRUITINGSan Antonio, Texas, 78207, United States
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Children's Hospital of The King's Daughters
RECRUITINGNorfolk, Virginia, 23507, United States
Contact Email: •••••@•••••
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Children's Hospital of Wisconsin
RECRUITINGMilwaukee, Wisconsin, 53226, United States
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Children's Hospitals and Clinics of Minnesota - Minneapolis
RECRUITINGMinneapolis, Minnesota, 55404, United States
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Children's Mercy Hospitals and Clinics
RECRUITINGKansas City, Missouri, 64108, United States
Contact Email: •••••@•••••
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Children's National Medical Center
RECRUITINGWashington D.C., District of Columbia, 20010, United States
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Christchurch Hospital
RECRUITINGChristchurch, 8011, New Zealand
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Cincinnati Children's Hospital Medical Center
RECRUITINGCincinnati, Ohio, 45229, United States
Contact Email: •••••@•••••
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Connecticut Children's Medical Center
RECRUITINGHartford, Connecticut, 06106, United States
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Cook Children's Medical Center
RECRUITINGFort Worth, Texas, 76104, United States
Contact Email: •••••@•••••
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Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
RECRUITINGGrand Rapids, Michigan, 49503, United States
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Dana-Farber Cancer Institute
RECRUITINGBoston, Massachusetts, 02215, United States
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Dayton Children's Hospital
RECRUITINGDayton, Ohio, 45404, United States
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Dell Children's Medical Center of Central Texas
RECRUITINGAustin, Texas, 78723, United States
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Driscoll Children's Hospital
RECRUITINGCorpus Christi, Texas, 78411, United States
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East Carolina University
RECRUITINGGreenville, North Carolina, 27834, United States
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East Tennessee Childrens Hospital
RECRUITINGKnoxville, Tennessee, 37916, United States
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Eastern Maine Medical Center
RECRUITINGBangor, Maine, 04401, United States
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El Paso Children's Hospital
RECRUITINGEl Paso, Texas, 79905, United States
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Geisinger Medical Center
RECRUITINGDanville, Pennsylvania, 17822, United States
Contact Email: •••••@•••••
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Golisano Children's Hospital of Southwest Florida
RECRUITINGFort Myers, Florida, 33908, United States
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Hackensack University Medical Center
RECRUITINGHackensack, New Jersey, 07601, United States
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Hospital for Sick Children
SUSPENDEDToronto, Ontario, M5G 1X8, Canada
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IWK Health Centre
RECRUITINGHalifax, Nova Scotia, B3K 6R8, Canada
Contact Email: •••••@•••••
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Jim Pattison Children's Hospital
RECRUITINGSaskatoon, Saskatchewan, S7N 0W8, Canada
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Johns Hopkins All Children's Hospital
RECRUITINGSt. Petersburg, Florida, 33701, United States
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Johns Hopkins University/Sidney Kimmel Cancer Center
RECRUITINGBaltimore, Maryland, 21287, United States
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Kaiser Permanente-Oakland
RECRUITINGOakland, California, 94611, United States
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Kapiolani Medical Center for Women and Children
RECRUITINGHonolulu, Hawaii, 96826, United States
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Laura and Isaac Perlmutter Cancer Center at NYU Langone
SUSPENDEDNew York, New York, 10016, United States
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Legacy Emanuel Children's Hospital
RECRUITINGPortland, Oregon, 97227, United States
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Loma Linda University Medical Center
RECRUITINGLoma Linda, California, 92354, United States
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Lucile Packard Children's Hospital Stanford University
RECRUITINGPalo Alto, California, 94304, United States
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Maine Children's Cancer Program
RECRUITINGScarborough, Maine, 04074, United States
Contact Email: •••••@•••••
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Mary Bridge Children's Hospital and Health Center
RECRUITINGTacoma, Washington, 98405, United States
Contact Email: •••••@•••••
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McMaster Children's Hospital at Hamilton Health Sciences
SUSPENDEDHamilton, Ontario, L8N 3Z5, Canada
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Medical City Dallas Hospital
RECRUITINGDallas, Texas, 75230, United States
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Memorial Sloan Kettering Cancer Center
RECRUITINGNew York, New York, 10065, United States
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Mercy Hospital Saint Louis
RECRUITINGSt Louis, Missouri, 63141, United States
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Miami Cancer Institute
ACTIVE_NOT_RECRUITINGMiami, Florida, 33176, United States
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Miller Children's and Women's Hospital Long Beach
RECRUITINGLong Beach, California, 90806, United States
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Montefiore Medical Center - Moses Campus
RECRUITINGThe Bronx, New York, 10467, United States
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Morristown Medical Center
RECRUITINGMorristown, New Jersey, 07960, United States
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NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
RECRUITINGNew York, New York, 10032, United States
Contact Email: •••••@•••••
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Nationwide Children's Hospital
RECRUITINGColumbus, Ohio, 43205, United States
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Nemours Children's Clinic-Jacksonville
RECRUITINGJacksonville, Florida, 32207, United States
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Nemours Children's Hospital
RECRUITINGOrlando, Florida, 32827, United States
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Newark Beth Israel Medical Center
RECRUITINGNewark, New Jersey, 07112, United States
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Norton Children's Hospital
RECRUITINGLouisville, Kentucky, 40202, United States
Contact Email: •••••@•••••
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Novant Health Presbyterian Medical Center
RECRUITINGCharlotte, North Carolina, 28204, United States
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OSF Children's Hospital of Illinois
RECRUITINGPeoria, Illinois, 61637, United States
Contact Email: •••••@•••••
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Oregon Health and Science University
RECRUITINGPortland, Oregon, 97239, United States
Contact Email: •••••@•••••
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Perth Children's Hospital
RECRUITINGPerth, Western Australia, 6009, Australia
Contact Email: •••••@•••••
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Phoenix Childrens Hospital
ACTIVE_NOT_RECRUITINGPhoenix, Arizona, 85016, United States
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Primary Children's Hospital
RECRUITINGSalt Lake City, Utah, 84113, United States
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Prisma Health Richland Hospital
RECRUITINGColumbia, South Carolina, 29203, United States
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ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
RECRUITINGToledo, Ohio, 43606, United States
Contact Email: •••••@•••••
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Providence Sacred Heart Medical Center and Children's Hospital
RECRUITINGSpokane, Washington, 99204, United States
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Queensland Children's Hospital
RECRUITINGSouth Brisbane, Queensland, 4101, Australia
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Rady Children's Hospital - San Diego
RECRUITINGSan Diego, California, 92123, United States
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Rainbow Babies and Childrens Hospital
RECRUITINGCleveland, Ohio, 44106, United States
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Rhode Island Hospital
RECRUITINGProvidence, Rhode Island, 02903, United States
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Riley Hospital for Children
RECRUITINGIndianapolis, Indiana, 46202, United States
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Roswell Park Cancer Institute
RECRUITINGBuffalo, New York, 14263, United States
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Royal Children's Hospital
RECRUITINGParkville, Victoria, 3052, Australia
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Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
RECRUITINGNew Brunswick, New Jersey, 08903, United States
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Saint Christopher's Hospital for Children
RECRUITINGPhiladelphia, Pennsylvania, 19134, United States
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Saint Joseph's Hospital/Children's Hospital-Tampa
RECRUITINGTampa, Florida, 33607, United States
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Saint Joseph's Regional Medical Center
RECRUITINGPaterson, New Jersey, 07503, United States
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Saint Jude Children's Research Hospital
RECRUITINGMemphis, Tennessee, 38105, United States
Contact Email: •••••@•••••
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Saint Luke's Cancer Institute - Boise
RECRUITINGBoise, Idaho, 83712, United States
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Sanford Broadway Medical Center
RECRUITINGFargo, North Dakota, 58122, United States
Contact Email: •••••@•••••
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Sanford USD Medical Center - Sioux Falls
RECRUITINGSioux Falls, South Dakota, 57117-5134, United States
Contact Email: •••••@•••••
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Seattle Children's Hospital
RECRUITINGSeattle, Washington, 98105, United States
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Starship Children's Hospital
RECRUITINGGrafton, Auckland, 1145, New Zealand
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State University of New York Upstate Medical University
RECRUITINGSyracuse, New York, 13210, United States
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Sydney Children's Hospital
RECRUITINGRandwick, New South Wales, 2031, Australia
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The Children's Hospital at TriStar Centennial
RECRUITINGNashville, Tennessee, 37203, United States
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The Children's Hospital at Westmead
RECRUITINGWestmead, New South Wales, 2145, Australia
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The Montreal Children's Hospital of the MUHC
RECRUITINGMontreal, Quebec, H3H 1P3, Canada
Contact Email: •••••@•••••
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The Steven and Alexandra Cohen Children's Medical Center of New York
RECRUITINGNew Hyde Park, New York, 11040, United States
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UCSF Benioff Children's Hospital Oakland
RECRUITINGOakland, California, 94609, United States
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UCSF Medical Center-Mission Bay
RECRUITINGSan Francisco, California, 94158, United States
Contact Email: •••••@•••••
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UT MD Anderson Cancer Center
RECRUITINGHouston, Texas, 77030, United States
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UT Southwestern/Simmons Cancer Center-Dallas
RECRUITINGDallas, Texas, 75390, United States
Contact Email: •••••@•••••
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University of Alberta Hospital
RECRUITINGEdmonton, Alberta, T6G 2B7, Canada
Contact Email: •••••@•••••
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University of Chicago Comprehensive Cancer Center
RECRUITINGChicago, Illinois, 60637, United States
Contact Email: •••••@•••••
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University of Iowa/Holden Comprehensive Cancer Center
RECRUITINGIowa City, Iowa, 52242, United States
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University of Kentucky/Markey Cancer Center
RECRUITINGLexington, Kentucky, 40536, United States
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University of Miami Miller School of Medicine-Sylvester Cancer Center
RECRUITINGMiami, Florida, 33136, United States
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University of Minnesota/Masonic Cancer Center
RECRUITINGMinneapolis, Minnesota, 55455, United States
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University of Mississippi Medical Center
RECRUITINGJackson, Mississippi, 39216, United States
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University of Nebraska Medical Center
RECRUITINGOmaha, Nebraska, 68198, United States
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University of Oklahoma Health Sciences Center
RECRUITINGOklahoma City, Oklahoma, 73104, United States
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University of Texas Health Science Center at San Antonio
RECRUITINGSan Antonio, Texas, 78229, United States
Contact Email: •••••@•••••
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University of Virginia Cancer Center
RECRUITINGCharlottesville, Virginia, 22908, United States
Contact Email: •••••@•••••
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University of Wisconsin Carbone Cancer Center - University Hospital
RECRUITINGMadison, Wisconsin, 53792, United States
Contact Email: •••••@•••••
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Wake Forest University Health Sciences
RECRUITINGWinston-Salem, North Carolina, 27157, United States
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Washington University School of Medicine
RECRUITINGSt Louis, Missouri, 63110, United States
Contact Email: •••••@•••••
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Yale University
RECRUITINGNew Haven, Connecticut, 06520, United States
Contact Email: •••••@•••••
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