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RECRUITING

NCT05099003

PHASE1/PHASE2

A Study of the Drug Selinexor With Radiation Therapy in Patients With Newly-Diagnosed Diffuse Intrinsic Pontine (DIPG) Glioma and High-Grade Glioma (HGG)

Sponsor: National Cancer Institute (NCI)

View on ClinicalTrials.gov

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.

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)

Key Details

Gender

All

Age Range

12 Months - 21 Years

Study Type

INTERVENTIONAL

Enrollment

132

Start Date

2022-05-31

Completion Date

2027-06-30

Last Updated

2026-04-09

Healthy Volunteers

Conditions

Malignant Glioma

Interventions

PROCEDURE

Biopsy Procedure

Undergo a biopsy

PROCEDURE

Magnetic Resonance Imaging

Undergo a MRI

RADIATION

Radiation Therapy

Undergo radiation therapy

DRUG

Selinexor

Given orally

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.

Locations (127)

Children's Hospital of Alabama

Birmingham, Alabama, United States

Banner Children's at Desert

Mesa, Arizona, United States

Phoenix Childrens Hospital

Phoenix, Arizona, United States

Arkansas Children's Hospital

Little Rock, Arkansas, United States

Loma Linda University Medical Center

Loma Linda, California, United States

Miller Children's and Women's Hospital Long Beach

Long Beach, California, United States

Children's Hospital Los Angeles

Los Angeles, California, United States

Cedars Sinai Medical Center

Los Angeles, California, United States

UCSF Benioff Children's Hospital Oakland

Oakland, California, United States

Kaiser Permanente-Oakland

Oakland, California, United States

Children's Hospital of Orange County

Orange, California, United States

Lucile Packard Children's Hospital Stanford University

Palo Alto, California, United States

Rady Children's Hospital - San Diego

San Diego, California, United States

UCSF Medical Center-Mission Bay

San Francisco, California, United States

Children's Hospital Colorado

Aurora, Colorado, United States

Connecticut Children's Medical Center

Hartford, Connecticut, United States

Yale University

New Haven, Connecticut, United States

Alfred I duPont Hospital for Children

Wilmington, Delaware, United States

Children's National Medical Center

Washington D.C., District of Columbia, United States

Golisano Children's Hospital of Southwest Florida

Fort Myers, Florida, United States

Nemours Children's Clinic-Jacksonville

Jacksonville, Florida, United States

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, United States

Miami Cancer Institute

Miami, Florida, United States

Arnold Palmer Hospital for Children

Orlando, Florida, United States

Nemours Children's Hospital

Orlando, Florida, United States

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, United States

Saint Joseph's Hospital/Children's Hospital-Tampa

Tampa, Florida, United States

Children's Healthcare of Atlanta - Arthur M Blank Hospital

Atlanta, Georgia, United States

Kapiolani Medical Center for Women and Children

Honolulu, Hawaii, United States

Saint Luke's Cancer Institute - Boise

Boise, Idaho, United States

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Saint Jude Midwest Affiliate

Peoria, Illinois, United States

Riley Hospital for Children

Indianapolis, Indiana, United States

Blank Children's Hospital

Des Moines, Iowa, United States

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, United States

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, United States

Norton Children's Hospital

Louisville, Kentucky, United States

Children's Hospital New Orleans

New Orleans, Louisiana, United States

Eastern Maine Medical Center

Bangor, Maine, United States

Maine Children's Cancer Program

Scarborough, Maine, United States

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

C S Mott Children's Hospital

Ann Arbor, Michigan, United States

Children's Hospital of Michigan

Detroit, Michigan, United States

Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital

Grand Rapids, Michigan, United States

Children's Hospitals and Clinics of Minnesota - Minneapolis

Minneapolis, Minnesota, United States

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, United States

University of Mississippi Medical Center

Jackson, Mississippi, United States

Children's Mercy Hospitals and Clinics

Kansas City, Missouri, United States

Cardinal Glennon Children's Medical Center

St Louis, Missouri, United States

Washington University School of Medicine

St Louis, Missouri, United States

Mercy Hospital Saint Louis

St Louis, Missouri, United States

Children's Hospital and Medical Center of Omaha

Omaha, Nebraska, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

Morristown Medical Center

Morristown, New Jersey, United States

Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital

New Brunswick, New Jersey, United States

Newark Beth Israel Medical Center

Newark, New Jersey, United States

Saint Joseph's Regional Medical Center

Paterson, New Jersey, United States

Albany Medical Center

Albany, New York, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

The Steven and Alexandra Cohen Children's Medical Center of New York

New Hyde Park, New York, United States

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, United States

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

State University of New York Upstate Medical University

Syracuse, New York, United States

Montefiore Medical Center - Moses Campus

The Bronx, New York, United States

Novant Health Presbyterian Medical Center

Charlotte, North Carolina, United States

East Carolina University

Greenville, North Carolina, United States

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Sanford Broadway Medical Center

Fargo, North Dakota, United States

Children's Hospital Medical Center of Akron

Akron, Ohio, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Rainbow Babies and Childrens Hospital

Cleveland, Ohio, United States

Nationwide Children's Hospital

Columbus, Ohio, United States

Dayton Children's Hospital

Dayton, Ohio, United States

ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital

Toledo, Ohio, United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Legacy Emanuel Children's Hospital

Portland, Oregon, United States

Oregon Health and Science University

Portland, Oregon, United States

Geisinger Medical Center

Danville, Pennsylvania, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Saint Christopher's Hospital for Children

Philadelphia, Pennsylvania, United States

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Rhode Island Hospital

Providence, Rhode Island, United States

Prisma Health Richland Hospital

Columbia, South Carolina, United States

BI-LO Charities Children's Cancer Center

Greenville, South Carolina, United States

Sanford USD Medical Center - Sioux Falls

Sioux Falls, South Dakota, United States

East Tennessee Childrens Hospital

Knoxville, Tennessee, United States

Saint Jude Children's Research Hospital

Memphis, Tennessee, United States

The Children's Hospital at TriStar Centennial

Nashville, Tennessee, United States

Dell Children's Medical Center of Central Texas

Austin, Texas, United States

Driscoll Children's Hospital

Corpus Christi, Texas, United States

Medical City Dallas Hospital

Dallas, Texas, United States

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, United States

El Paso Children's Hospital

El Paso, Texas, United States

Cook Children's Medical Center

Fort Worth, Texas, United States

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, United States

M D Anderson Cancer Center

Houston, Texas, United States

Children's Hospital of San Antonio

San Antonio, Texas, United States

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Primary Children's Hospital

Salt Lake City, Utah, United States

University of Virginia Cancer Center

Charlottesville, Virginia, United States

Children's Hospital of The King's Daughters

Norfolk, Virginia, United States

Seattle Children's Hospital

Seattle, Washington, United States

Providence Sacred Heart Medical Center and Children's Hospital

Spokane, Washington, United States

Mary Bridge Children's Hospital and Health Center

Tacoma, Washington, United States

University of Wisconsin Carbone Cancer Center - University Hospital

Madison, Wisconsin, United States

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States

Sydney Children's Hospital

Randwick, New South Wales, Australia

The Children's Hospital at Westmead

Westmead, New South Wales, Australia

Queensland Children's Hospital

South Brisbane, Queensland, Australia

Royal Children's Hospital

Parkville, Victoria, Australia

Perth Children's Hospital

Perth, Western Australia, Australia

University of Alberta Hospital

Edmonton, Alberta, Canada

British Columbia Children's Hospital

Vancouver, British Columbia, Canada

CancerCare Manitoba

Winnipeg, Manitoba, Canada

IWK Health Centre

Halifax, Nova Scotia, Canada

McMaster Children's Hospital at Hamilton Health Sciences

Hamilton, Ontario, Canada

Hospital for Sick Children

Toronto, Ontario, Canada

The Montreal Children's Hospital of the MUHC

Montreal, Quebec, Canada

Centre Hospitalier Universitaire Sainte-Justine

Montreal, Quebec, Canada

Centre Hospitalier Universitaire de Sherbrooke-Fleurimont

Sherbrooke, Quebec, Canada

Jim Pattison Children's Hospital

Saskatoon, Saskatchewan, Canada

CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)

Québec, Canada

Starship Children's Hospital

Grafton, Auckland, New Zealand

Christchurch Hospital

Christchurch, New Zealand

Clinical Research Directory

A Study of the Drug Selinexor With Radiation Therapy in Patients With Newly-Diagnosed Diffuse Intrinsic Pontine (DIPG) Glioma and High-Grade Glioma (HGG)

Summary

Key Details

Conditions

Interventions

Eligibility Criteria

Locations (127)