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)

Who is this study for? Patients with Malignant Glioma, Anaplastic Astrocytoma
What treatments are being studied? Biopsy+Magnetic Resonance Imaging+Radiation Therapy+Selinexor
Status: Recruiting
Location: See all (121) locations...
Intervention Type: Drug, Radiation, Procedure
Study Type: Interventional
Study Phase: Phase 1/Phase 2
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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 1
Maximum Age: 21
Healthy Volunteers: f
View:

• 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. 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)

• 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. 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

⁃ \>= 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.

Locations
United States
Alabama
Children's Hospital of Alabama
RECRUITING
Birmingham
Arkansas
Arkansas Children's Hospital
RECRUITING
Little Rock
Arizona
Banner Children's at Desert
RECRUITING
Mesa
California
Loma Linda University Medical Center
RECRUITING
Loma Linda
Miller Children's and Women's Hospital Long Beach
RECRUITING
Long Beach
Children's Hospital Los Angeles
RECRUITING
Los Angeles
Kaiser Permanente-Oakland
RECRUITING
Oakland
UCSF Benioff Children's Hospital Oakland
RECRUITING
Oakland
Children's Hospital of Orange County
RECRUITING
Orange
Lucile Packard Children's Hospital Stanford University
RECRUITING
Palo Alto
Rady Children's Hospital - San Diego
SUSPENDED
San Diego
UCSF Medical Center-Mission Bay
RECRUITING
San Francisco
Colorado
Children's Hospital Colorado
RECRUITING
Aurora
Connecticut
Connecticut Children's Medical Center
RECRUITING
Hartford
Yale University
RECRUITING
New Haven
Washington, D.c.
Children's National Medical Center
RECRUITING
Washington
Delaware
Alfred I duPont Hospital for Children
RECRUITING
Wilmington
Florida
Golisano Children's Hospital of Southwest Florida
RECRUITING
Fort Myers
Nemours Children's Clinic-Jacksonville
RECRUITING
Jacksonville
Miami Cancer Institute
RECRUITING
Miami
University of Miami Miller School of Medicine-Sylvester Cancer Center
RECRUITING
Miami
Arnold Palmer Hospital for Children
RECRUITING
Orlando
Nemours Children's Hospital
RECRUITING
Orlando
Johns Hopkins All Children's Hospital
RECRUITING
Saint Petersburg
Georgia
Children's Healthcare of Atlanta - Arthur M Blank Hospital
RECRUITING
Atlanta
Hawaii
Kapiolani Medical Center for Women and Children
RECRUITING
Honolulu
Iowa
Blank Children's Hospital
RECRUITING
Des Moines
University of Iowa/Holden Comprehensive Cancer Center
RECRUITING
Iowa City
Idaho
Saint Luke's Cancer Institute - Boise
RECRUITING
Boise
Illinois
University of Chicago Comprehensive Cancer Center
RECRUITING
Chicago
Saint Jude Midwest Affiliate
RECRUITING
Peoria
Indiana
Riley Hospital for Children
RECRUITING
Indianapolis
Kentucky
University of Kentucky/Markey Cancer Center
RECRUITING
Lexington
Norton Children's Hospital
RECRUITING
Louisville
Louisiana
Children's Hospital New Orleans
RECRUITING
New Orleans
Massachusetts
Dana-Farber Cancer Institute
RECRUITING
Boston
Maryland
Johns Hopkins University/Sidney Kimmel Cancer Center
RECRUITING
Baltimore
Maine
Eastern Maine Medical Center
RECRUITING
Bangor
Maine Children's Cancer Program
RECRUITING
Scarborough
Michigan
C S Mott Children's Hospital
RECRUITING
Ann Arbor
Children's Hospital of Michigan
RECRUITING
Detroit
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
RECRUITING
Grand Rapids
Minnesota
Children's Hospitals and Clinics of Minnesota - Minneapolis
RECRUITING
Minneapolis
University of Minnesota/Masonic Cancer Center
RECRUITING
Minneapolis
Missouri
Children's Mercy Hospitals and Clinics
RECRUITING
Kansas City
Cardinal Glennon Children's Medical Center
RECRUITING
Saint Louis
Mercy Hospital Saint Louis
RECRUITING
Saint Louis
Washington University School of Medicine
RECRUITING
Saint Louis
Mississippi
University of Mississippi Medical Center
RECRUITING
Jackson
North Carolina
Novant Health Presbyterian Medical Center
RECRUITING
Charlotte
East Carolina University
SUSPENDED
Greenville
Wake Forest University Health Sciences
RECRUITING
Winston-salem
North Dakota
Sanford Broadway Medical Center
RECRUITING
Fargo
Nebraska
Children's Hospital and Medical Center of Omaha
RECRUITING
Omaha
University of Nebraska Medical Center
RECRUITING
Omaha
New Jersey
Hackensack University Medical Center
RECRUITING
Hackensack
Morristown Medical Center
RECRUITING
Morristown
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
RECRUITING
New Brunswick
Newark Beth Israel Medical Center
RECRUITING
Newark
Saint Joseph's Regional Medical Center
RECRUITING
Paterson
New York
Albany Medical Center
RECRUITING
Albany
Montefiore Medical Center - Moses Campus
SUSPENDED
Bronx
Roswell Park Cancer Institute
RECRUITING
Buffalo
The Steven and Alexandra Cohen Children's Medical Center of New York
RECRUITING
New Hyde Park
Memorial Sloan Kettering Cancer Center
RECRUITING
New York
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
RECRUITING
New York
State University of New York Upstate Medical University
RECRUITING
Syracuse
Ohio
Children's Hospital Medical Center of Akron
RECRUITING
Akron
Cincinnati Children's Hospital Medical Center
RECRUITING
Cincinnati
Rainbow Babies and Childrens Hospital
RECRUITING
Cleveland
Nationwide Children's Hospital
RECRUITING
Columbus
Dayton Children's Hospital
RECRUITING
Dayton
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
RECRUITING
Toledo
Oklahoma
University of Oklahoma Health Sciences Center
RECRUITING
Oklahoma City
Oregon
Legacy Emanuel Children's Hospital
RECRUITING
Portland
Oregon Health and Science University
RECRUITING
Portland
Pennsylvania
Geisinger Medical Center
RECRUITING
Danville
Children's Hospital of Philadelphia
RECRUITING
Philadelphia
Saint Christopher's Hospital for Children
RECRUITING
Philadelphia
Children's Hospital of Pittsburgh of UPMC
RECRUITING
Pittsburgh
Rhode Island
Rhode Island Hospital
RECRUITING
Providence
South Carolina
Prisma Health Richland Hospital
RECRUITING
Columbia
BI-LO Charities Children's Cancer Center
RECRUITING
Greenville
South Dakota
Sanford USD Medical Center - Sioux Falls
RECRUITING
Sioux Falls
Tennessee
East Tennessee Childrens Hospital
RECRUITING
Knoxville
Saint Jude Children's Research Hospital
RECRUITING
Memphis
The Children's Hospital at TriStar Centennial
RECRUITING
Nashville
Texas
Dell Children's Medical Center of Central Texas
RECRUITING
Austin
Medical City Dallas Hospital
RECRUITING
Dallas
UT Southwestern/Simmons Cancer Center-Dallas
SUSPENDED
Dallas
El Paso Children's Hospital
RECRUITING
El Paso
Cook Children's Medical Center
RECRUITING
Fort Worth
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
RECRUITING
Houston
M D Anderson Cancer Center
RECRUITING
Houston
Children's Hospital of San Antonio
RECRUITING
San Antonio
University of Texas Health Science Center at San Antonio
RECRUITING
San Antonio
Utah
Primary Children's Hospital
RECRUITING
Salt Lake City
Virginia
University of Virginia Cancer Center
RECRUITING
Charlottesville
Children's Hospital of The King's Daughters
RECRUITING
Norfolk
Washington
Seattle Children's Hospital
RECRUITING
Seattle
Providence Sacred Heart Medical Center and Children's Hospital
RECRUITING
Spokane
Mary Bridge Children's Hospital and Health Center
RECRUITING
Tacoma
Wisconsin
University of Wisconsin Carbone Cancer Center - University Hospital
RECRUITING
Madison
Children's Hospital of Wisconsin
RECRUITING
Milwaukee
Other Locations
Australia
Royal Children's Hospital
RECRUITING
Parkville
Perth Children's Hospital
RECRUITING
Perth
Sydney Children's Hospital
RECRUITING
Randwick
Queensland Children's Hospital
RECRUITING
South Brisbane
The Children's Hospital at Westmead
RECRUITING
Westmead
Canada
University of Alberta Hospital
RECRUITING
Edmonton
IWK Health Centre
RECRUITING
Halifax
Centre Hospitalier Universitaire Sainte-Justine
RECRUITING
Montreal
The Montreal Children's Hospital of the MUHC
RECRUITING
Montreal
CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
RECRUITING
Quebec
Jim Pattison Children's Hospital
RECRUITING
Saskatoon
Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
RECRUITING
Sherbrooke
Hospital for Sick Children
RECRUITING
Toronto
British Columbia Children's Hospital
RECRUITING
Vancouver
CancerCare Manitoba
RECRUITING
Winnipeg
New Zealand
Christchurch Hospital
RECRUITING
Christchurch
Starship Children's Hospital
RECRUITING
Grafton
Time Frame
Start Date: 2022-05-31
Estimated Completion Date: 2027-06-30
Participants
Target number of participants: 210
Treatments
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.
Authors
Sponsors
Leads: National Cancer Institute (NCI)

This content was sourced from clinicaltrials.gov

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