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 Purpose
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.
Recruitment Criteria
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Accepts Healthy Volunteers
Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms |
No |
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Study Type
An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies. |
Interventional |
| Eligible Ages | 12 Months - 21 Years |
| Gender | All |
Inclusion Criteria:
- - PRE ENROLLMENT: Patients must be =< 25 years of age at the time of enrollment on APEC14B1 part A cnetral 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.
- - 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) - 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.
- - 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.
- - 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.
- - 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.
- - 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.
- - STEP 1: Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2.
- - 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.
- - 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.
- - 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).
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.
- - 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.
Trial Details
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Trial ID:
This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries. |
NCT05099003 |
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Phase
Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use. |
Phase 1/Phase 2 |
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Lead Sponsor
The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data. |
National Cancer Institute (NCI) |
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Principal Investigator
The person who is responsible for the scientific and technical direction of the entire clinical study. |
Adam L Green |
| Principal Investigator Affiliation | Children's Oncology Group |
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Agency Class
Category of organization(s) involved as sponsor (and collaborator) supporting the trial. |
NIH |
| Overall Status | Suspended |
| Countries | Australia, Canada, New Zealand, United States |
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Conditions
The disease, disorder, syndrome, illness, or injury that is being studied. |
Anaplastic Astrocytoma, Anaplastic Astrocytoma, Not Otherwise Specified, Diffuse Intrinsic Pontine Glioma, Diffuse Midline Glioma, H3 K27M-Mutant, Glioblastoma, Glioblastoma, Not Otherwise Specified, Malignant Glioma |
PRIMARY OBJECTIVES:
- I. To define toxicities and estimate the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of selinexor administered as an oral formulation in combination with standard of care radiation therapy (RT), to pediatric patients with newly diagnosed high-grade glioma (HGG) or diffuse intrinsic pontine glioma (DIPG).
- II. To estimate the event-free survival (EFS) distribution for diffuse midline glioma (DMG)/HGG patients and overall survival (OS) distribution for DIPG patients associated with selinexor plus RT, followed by selinexor in patients with newly diagnosed HGG (H3 K27M mutant DMG or H3 K27-wild type HGG) or DIPG, and to compare those outcomes to historical controls.
- I. To bank tumor specimens and body fluids (blood and cerebrospinal fluid) for future studies.
Arms
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.
Interventions
Procedure: - Biopsy
Undergo a biopsy
Procedure: - Magnetic Resonance Imaging
Undergo a MRI
Radiation: - Radiation Therapy
Undergo radiation therapy
Drug: - Selinexor
Given orally
Contact a Trial Team
If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.
Status
Address
Children's Hospital of Alabama
Birmingham, Alabama, 35233
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Banner Children's at Desert
Mesa, Arizona, 85202
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Phoenix Childrens Hospital
Phoenix, Arizona, 85016
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Arkansas Children's Hospital
Little Rock, Arkansas, 72202-3591
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Address
Loma Linda University Medical Center
Loma Linda, California, 92354
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Address
Miller Children's and Women's Hospital Long Beach
Long Beach, California, 90806
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Address
Children's Hospital Los Angeles
Los Angeles, California, 90027
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Cedars Sinai Medical Center
Los Angeles, California, 90048
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UCSF Benioff Children's Hospital Oakland
Oakland, California, 94609
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Kaiser Permanente-Oakland
Oakland, California, 94611
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Children's Hospital of Orange County
Orange, California, 92868
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Lucile Packard Children's Hospital Stanford University
Palo Alto, California, 94304
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Rady Children's Hospital - San Diego
San Diego, California, 92123
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UCSF Medical Center-Mission Bay
San Francisco, California, 94158
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Children's Hospital Colorado
Aurora, Colorado, 80045
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Connecticut Children's Medical Center
Hartford, Connecticut, 06106
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Yale University
New Haven, Connecticut, 06520
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Alfred I duPont Hospital for Children
Wilmington, Delaware, 19803
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Children's National Medical Center
Washington, District of Columbia, 20010
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Golisano Children's Hospital of Southwest Florida
Fort Myers, Florida, 33908
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Address
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, 32207
Status
Address
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136
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Miami Cancer Institute
Miami, Florida, 33176
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Address
Arnold Palmer Hospital for Children
Orlando, Florida, 32806
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Address
Nemours Children's Hospital
Orlando, Florida, 32827
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Address
Johns Hopkins All Children's Hospital
Saint Petersburg, Florida, 33701
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Address
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta, Georgia, 30329
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Address
Kapiolani Medical Center for Women and Children
Honolulu, Hawaii, 96826
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Address
Saint Luke's Cancer Institute - Boise
Boise, Idaho, 83712
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Address
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
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Address
Saint Jude Midwest Affiliate
Peoria, Illinois, 61637
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Address
Riley Hospital for Children
Indianapolis, Indiana, 46202
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Address
Blank Children's Hospital
Des Moines, Iowa, 50309
Status
Address
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242
Status
Address
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536
Status
Address
Norton Children's Hospital
Louisville, Kentucky, 40202
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Address
Children's Hospital New Orleans
New Orleans, Louisiana, 70118
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Address
Eastern Maine Medical Center
Bangor, Maine, 04401
Status
Address
Maine Children's Cancer Program
Scarborough, Maine, 04074
Status
Address
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
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Address
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
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Address
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109
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Address
Children's Hospital of Michigan
Detroit, Michigan, 48201
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Address
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
Grand Rapids, Michigan, 49503
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Address
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, 55404
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University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, 55455
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University of Mississippi Medical Center
Jackson, Mississippi, 39216
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Address
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108
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Cardinal Glennon Children's Medical Center
Saint Louis, Missouri, 63104
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Washington University School of Medicine
Saint Louis, Missouri, 63110
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Address
Mercy Hospital Saint Louis
Saint Louis, Missouri, 63141
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Address
Children's Hospital and Medical Center of Omaha
Omaha, Nebraska, 68114
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Address
University of Nebraska Medical Center
Omaha, Nebraska, 68198
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Hackensack University Medical Center
Hackensack, New Jersey, 07601
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Address
Morristown Medical Center
Morristown, New Jersey, 07960
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Address
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
New Brunswick, New Jersey, 08903
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Newark Beth Israel Medical Center
Newark, New Jersey, 07112
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Address
Saint Joseph's Regional Medical Center
Paterson, New Jersey, 07503
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Albany Medical Center
Albany, New York, 12208
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Montefiore Medical Center - Moses Campus
Bronx, New York, 10467
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Address
Roswell Park Cancer Institute
Buffalo, New York, 14263
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Address
The Steven and Alexandra Cohen Children's Medical Center of New York
New Hyde Park, New York, 11040
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Address
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032
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Address
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Status
Address
State University of New York Upstate Medical University
Syracuse, New York, 13210
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Address
Novant Health Presbyterian Medical Center
Charlotte, North Carolina, 28204
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Address
East Carolina University
Greenville, North Carolina, 27834
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Address
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
Status
Address
Sanford Broadway Medical Center
Fargo, North Dakota, 58122
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Address
Children's Hospital Medical Center of Akron
Akron, Ohio, 44308
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Address
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
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Address
Rainbow Babies and Childrens Hospital
Cleveland, Ohio, 44106
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Address
Nationwide Children's Hospital
Columbus, Ohio, 43205
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Address
Dayton Children's Hospital
Dayton, Ohio, 45404
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Address
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
Toledo, Ohio, 43606
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University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
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Address
Legacy Emanuel Children's Hospital
Portland, Oregon, 97227
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Address
Oregon Health and Science University
Portland, Oregon, 97239
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Address
Geisinger Medical Center
Danville, Pennsylvania, 17822
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Address
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
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Address
Saint Christopher's Hospital for Children
Philadelphia, Pennsylvania, 19134
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Address
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
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Address
Rhode Island Hospital
Providence, Rhode Island, 02903
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Address
Prisma Health Richland Hospital
Columbia, South Carolina, 29203
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Address
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, 29605
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Address
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, 57117-5134
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Address
East Tennessee Childrens Hospital
Knoxville, Tennessee, 37916
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Address
Saint Jude Children's Research Hospital
Memphis, Tennessee, 38105
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Address
The Children's Hospital at TriStar Centennial
Nashville, Tennessee, 37203
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Address
Dell Children's Medical Center of Central Texas
Austin, Texas, 78723
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Address
Medical City Dallas Hospital
Dallas, Texas, 75230
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Address
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390
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Address
El Paso Children's Hospital
El Paso, Texas, 79905
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Address
Cook Children's Medical Center
Fort Worth, Texas, 76104
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Address
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030
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Address
M D Anderson Cancer Center
Houston, Texas, 77030
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Address
Children's Hospital of San Antonio
San Antonio, Texas, 78207
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Address
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229
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Address
Primary Children's Hospital
Salt Lake City, Utah, 84113
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Address
University of Virginia Cancer Center
Charlottesville, Virginia, 22908
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Address
Children's Hospital of The King's Daughters
Norfolk, Virginia, 23507
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Address
Seattle Children's Hospital
Seattle, Washington, 98105
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Address
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington, 99204
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Address
Mary Bridge Children's Hospital and Health Center
Tacoma, Washington, 98405
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Address
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792
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Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
International Sites
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Sydney Children's Hospital
Randwick, New South Wales, 2031
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The Children's Hospital at Westmead
Westmead, New South Wales, 2145
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Queensland Children's Hospital
South Brisbane, Queensland, 4101
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Royal Children's Hospital
Parkville, Victoria, 3052
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Perth Children's Hospital
Perth, Western Australia, 6009
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Address
University of Alberta Hospital
Edmonton, Alberta, T6G 2B7
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British Columbia Children's Hospital
Vancouver, British Columbia, V6H 3V4
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CancerCare Manitoba
Winnipeg, Manitoba, R3E 0V9
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Address
IWK Health Centre
Halifax, Nova Scotia, B3K 6R8
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Hospital for Sick Children
Toronto, Ontario, M5G 1X8
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The Montreal Children's Hospital of the MUHC
Montreal, Quebec, H3H 1P3
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Address
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, H3T 1C5
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Address
Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
Sherbrooke, Quebec, J1H 5N4
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Address
Jim Pattison Children's Hospital
Saskatoon, Saskatchewan, S7N 0W8
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Address
CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
Quebec, , G1V 4G2
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Address
Starship Children's Hospital
Grafton, Auckland, 1145
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Address
Christchurch Hospital
Christchurch, , 8011
