RECRUITING

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

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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)

Quick Facts

Study Start:2022-05-31
Study Completion:2027-06-30
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT05099003

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:12 Months to 21 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:CHILD, ADULT
Inclusion CriteriaExclusion Criteria
  1. * 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
  2. * Please note:
  3. * This required age range applies to pre-enrollment eligibility for all HGG patients. Individual treatment protocols may have different age criteria.
  4. * 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).
  5. * PRE ENROLLMENT: Patient is suspected of having localized, newly diagnosed HGG, excluding metastatic disease, OR patient has an institutional diagnosis of DIPG
  6. * Please note: there are specific radiographic criteria for DIPG patient enrollment on ACNS1821 (Step 1)
  7. * 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.
  8. * PRE ENROLLMENT:
  9. * 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.
  10. * For patients with DIPG: Patients and/or their parents or legal guardians must have signed informed consent for ACNS1821.
  11. * 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.
  12. * PRE ENROLLMENT:
  13. * 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
  14. * STEP 1: Patients must be \>= 12 months and =\< 21 years of age at the time of enrollment
  15. * STEP 1: Patients must have newly-diagnosed DIPG or HGG (including DMG).
  16. * STEP 1: Stratum DIPG (Closed with Amendment #4)
  17. * 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.
  18. * 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.
  19. * 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.
  20. * STEP 1: Stratum DMG (with H3 K27M mutation) (Closed with Amendment #4)
  21. * 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.
  22. * 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
  23. * 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.
  24. * STEP 1: Stratum HGG (without H3 K27M mutation)
  25. * 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
  26. * Please note:
  27. * 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
  28. * 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
  29. * 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.
  30. * STEP 1: Peripheral absolute neutrophil count (ANC) \>= 1000/uL (within 7 days prior to step 1 enrollment)
  31. * STEP 1: Platelet count \>= 100,000/uL (transfusion independent) (within 7 days prior to step 1 enrollment)
  32. * STEP 1: Hemoglobin \>= 8.0 g/dL (may receive red blood cell \[RBC\] transfusions) (within 7 days prior to step 1 enrollment)
  33. * 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
  34. * Age / Maximum Serum Creatinine (mg/dL)
  35. * 1 to \< 2 years / male: 0.6; female: 0.6
  36. * 2 to \< 6 years / male: 0.8; female: 0.8
  37. * 6 to \< 10 years / male: 1; female: 1
  38. * 10 to \< 13 years / male: 1.2; female: 1.2
  39. * 13 to \< 16 years / male: 1.5; female: 1.4
  40. * \>= 16 years / male: 1.7; female: 1.4
  41. * STEP 1: Total bilirubin =\< 1.5 x upper limit of normal (ULN) for age
  42. * 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.
  43. * STEP 1: Serum amylase =\< 1.5 x ULN
  44. * STEP 1: Serum lipase =\< 1.5 x ULN
  45. * STEP 1: No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry \> 94% if there is clinical indication for determination.
  46. * STEP 1: Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled.
  47. * 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).
  1. * STEP 1: Patients must not have received any prior therapy for their central nervous system (CNS) malignancy except for surgery and steroid medications.
  2. * STEP 1: Patients who are currently receiving another investigational drug are not eligible.
  3. * STEP 1: Patients who are currently receiving other anti-cancer agents are not eligible.
  4. * STEP 1: Patients \>=18 years of age who have H3 K27M-wild type HGG.
  5. * STEP 1: Patients who have an uncontrolled infection.
  6. * STEP 1: Patients who have received a prior solid organ transplantation.
  7. * STEP 1: Patients with grade \> 1 extrapyramidal movement disorder.
  8. * STEP 1: Patients with known macular degeneration, uncontrolled glaucoma, or cataracts.
  9. * 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.
  10. * STEP 1: Patients with gliomatosis cerebri type 1 or 2 are not eligible, with the exception of H3 K27M-mutant bithalamic tumors.
  11. * STEP 1: Patients who are not able to receive protocol specified radiation therapy.
  12. * STEP 1:
  13. * Female patients who are pregnant are ineligible since there is yet no available information regarding human fetal or teratogenic toxicities.
  14. * 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.
  15. * Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained.
  16. * 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.

Contacts and Locations

Principal Investigator

Adam L Green
PRINCIPAL_INVESTIGATOR
Children's Oncology Group

Study Locations (Sites)

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, 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
Saint Petersburg, Florida, 33701
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
Saint Jude Midwest Affiliate
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
Saint Louis, Missouri, 63104
United States
Washington University School of Medicine
Saint Louis, Missouri, 63110
United States
Mercy Hospital Saint Louis
Saint 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
Montefiore Medical Center - Moses Campus
Bronx, New York, 10467
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
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
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
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

Collaborators and Investigators

Sponsor: National Cancer Institute (NCI)

  • Adam L Green, PRINCIPAL_INVESTIGATOR, Children's Oncology Group

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-05-31
Study Completion Date2027-06-30

Study Record Updates

Study Start Date2022-05-31
Study Completion Date2027-06-30

Terms related to this study

Additional Relevant MeSH Terms

  • Malignant Glioma