A Study of the Drug Selinexor With Radiation Therapy in Patients With Newly-Diagnosed Diffuse Intrinsic Pontine (DIPG) Glioma and High-Grade Glioma (HGG)
Anaplastic Astrocytoma, Anaplastic Astrocytoma, Not Otherwise Specified, Diffuse Intrinsic Pontine Glioma
About this trial
This is an interventional treatment trial for Anaplastic Astrocytoma
Eligibility Criteria
Inclusion Criteria:
STEP 0: Patients must be >= 12 months and =< 21 years of age at the time of enrollment on Step 0.
Please note:
- This age range includes pre-screening 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).
- STEP 0: Patient is suspected of having localized, newly diagnosed HGG, excluding metastatic disease, OR patient has an institutional diagnosis of DIPG
STEP 0:
- For patients with non-pontine tumors: Patient and/or their parents or legal guardians have signed informed consent for eligibility screening on APEC14B1 Part A.
- For patients with DIPG: Patient and/or their parents or legal guardians have signed informed consent for ACNS1821.
STEP 0:
- 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
- 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)
- 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/gender 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.
Sites / Locations
- Children's Hospital of AlabamaRecruiting
- Banner Children's at DesertRecruiting
- Arkansas Children's HospitalRecruiting
- Loma Linda University Medical CenterRecruiting
- Children's Hospital Los AngelesRecruiting
- Kaiser Permanente-OaklandRecruiting
- Children's Hospital of Orange CountyRecruiting
- Rady Children's Hospital - San DiegoRecruiting
- UCSF Medical Center-Mission BayRecruiting
- Connecticut Children's Medical CenterRecruiting
- Yale UniversityRecruiting
- Alfred I duPont Hospital for ChildrenRecruiting
- Children's National Medical CenterRecruiting
- Golisano Children's Hospital of Southwest FloridaRecruiting
- Nemours Children's Clinic-JacksonvilleRecruiting
- Miami Cancer InstituteRecruiting
- Arnold Palmer Hospital for ChildrenRecruiting
- Nemours Children's HospitalRecruiting
- Johns Hopkins All Children's HospitalRecruiting
- Kapiolani Medical Center for Women and ChildrenRecruiting
- Saint Luke's Cancer Institute - BoiseRecruiting
- University of Chicago Comprehensive Cancer CenterRecruiting
- Saint Jude Midwest AffiliateRecruiting
- Riley Hospital for ChildrenRecruiting
- University of Iowa/Holden Comprehensive Cancer CenterRecruiting
- Norton Children's HospitalRecruiting
- Children's Hospital New OrleansRecruiting
- Eastern Maine Medical Center
- Maine Children's Cancer ProgramRecruiting
- Johns Hopkins University/Sidney Kimmel Cancer CenterRecruiting
- C S Mott Children's HospitalRecruiting
- Children's Hospital of MichiganRecruiting
- Helen DeVos Children's Hospital at Spectrum HealthRecruiting
- Children's Hospitals and Clinics of Minnesota - MinneapolisRecruiting
- University of Minnesota/Masonic Cancer CenterRecruiting
- University of Mississippi Medical CenterRecruiting
- Children's Mercy Hospitals and ClinicsRecruiting
- Cardinal Glennon Children's Medical CenterRecruiting
- Washington University School of MedicineRecruiting
- Mercy Hospital Saint LouisRecruiting
- Children's Hospital and Medical Center of OmahaRecruiting
- University of Nebraska Medical CenterRecruiting
- Hackensack University Medical CenterRecruiting
- Morristown Medical CenterRecruiting
- Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University HospitalRecruiting
- Saint Joseph's Regional Medical CenterRecruiting
- Albany Medical CenterRecruiting
- Montefiore Medical Center - Moses CampusRecruiting
- Roswell Park Cancer InstituteRecruiting
- The Steven and Alexandra Cohen Children's Medical Center of New YorkRecruiting
- Memorial Sloan Kettering Cancer CenterRecruiting
- State University of New York Upstate Medical UniversityRecruiting
- Wake Forest University Health SciencesRecruiting
- Sanford Broadway Medical CenterRecruiting
- Children's Hospital Medical Center of AkronRecruiting
- Cincinnati Children's Hospital Medical CenterRecruiting
- Rainbow Babies and Childrens HospitalRecruiting
- Nationwide Children's HospitalRecruiting
- ProMedica Toledo Hospital/Russell J Ebeid Children's HospitalRecruiting
- University of Oklahoma Health Sciences CenterRecruiting
- Legacy Emanuel Children's HospitalRecruiting
- Oregon Health and Science UniversityRecruiting
- Saint Christopher's Hospital for ChildrenRecruiting
- Children's Hospital of Pittsburgh of UPMCRecruiting
- Rhode Island HospitalRecruiting
- Prisma Health Richland HospitalRecruiting
- BI-LO Charities Children's Cancer CenterRecruiting
- Sanford USD Medical Center - Sioux FallsRecruiting
- Saint Jude Children's Research HospitalRecruiting
- The Children's Hospital at TriStar CentennialRecruiting
- Dell Children's Medical Center of Central Texas
- Medical City Dallas HospitalRecruiting
- UT Southwestern/Simmons Cancer Center-DallasRecruiting
- Cook Children's Medical CenterRecruiting
- Baylor College of Medicine/Dan L Duncan Comprehensive Cancer CenterRecruiting
- Children's Hospital of San AntonioRecruiting
- University of Texas Health Science Center at San AntonioRecruiting
- Primary Children's HospitalRecruiting
- Children's Hospital of The King's DaughtersRecruiting
- Seattle Children's HospitalRecruiting
- Providence Sacred Heart Medical Center and Children's HospitalRecruiting
- Mary Bridge Children's Hospital and Health CenterRecruiting
- University of Wisconsin Carbone Cancer CenterRecruiting
- Children's Hospital of WisconsinRecruiting
- CancerCare ManitobaRecruiting
- IWK Health CentreRecruiting
- Centre Hospitalier Universitaire Sainte-JustineRecruiting
- CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)Recruiting
- Starship Children's HospitalRecruiting
- Christchurch HospitalRecruiting
Arms of the Study
Arm 1
Experimental
Treatment (selinexor and radiation therapy)
CHEMORADIOTHERAPY: Patients receive standard of care radiation therapy 5 days per week for 5-7 weeks. Starting on day 4 or 5 of radiation therapy, patients receive selinexor 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.