Veliparib, Radiation Therapy, and Temozolomide in Treating Patients With Newly Diagnosed Malignant Glioma Without H3 K27M or BRAFV600 Mutations
Anaplastic Astrocytoma, Glioblastoma, Malignant Glioma
About this trial
This is an interventional treatment trial for Anaplastic Astrocytoma
Eligibility Criteria
Inclusion Criteria:
Stratum 1 (IDH wild-type): Patients must be >= 3 years of age and =< 21 years of age at the time of enrollment
- Please note Stratum 1 was closed to accrual on January 24, 2020
- Stratum 2 (IDH mutant): Patients must be >= 3 years of age and =< 25 years of age at the time of enrollment
Patients must have eligibility confirmed by rapid central pathology and central molecular screening reviews performed on APEC14B1:
- Newly-diagnosed high-grade glioma such as anaplastic astrocytoma or glioblastoma
- Negative results for H3 K27M by immunohistochemistry (IHC)
- Negative results for BRAFV600 mutation by next-generation sequencing (NGS)
- Patients must have histological verification of diagnosis. Patients with M+ disease (defined as evidence of neuraxis dissemination) are not eligible. Cerebrospinal fluid (CSF) cytology is not required but may be obtained if clinically indicated prior to study enrollment. If cytology is positive, the patient would be considered to have metastatic disease and would, therefore, be ineligible
- Pre-operative and post-operative brain magnetic resonance imaging (MRI) with and without contrast must be obtained. The requirement for a post-operative MRI is waived for patients who undergo biopsy only. A spine MRI is not required, but may be obtained if clinically indicated. If the spine MRI is positive, the patient would be considered to have M+ disease (defined as neuraxis dissemination) and would be ineligible
- 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
- Peripheral absolute neutrophil count (ANC) >= 1,000/uL (within 7 days prior to enrollment)
- Platelet count >= 100,000/uL (transfusion independent) (within 7 days prior to enrollment)
- Hemoglobin >= 8.0 gm/dL (can be transfused) (within 7 days prior to enrollment)
Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 OR a serum creatinine based on age/gender as follows (within 7 days prior to enrollment):
- 3 to < 6 years: 0.8 (male and female) maximum serum creatinine (mg/dL)
- 6 to < 10 years: 1 (male and female) maximum serum creatinine (mg/dL)
- 10 to < 13 years: 1.2 (male and female) maximum serum creatinine (mg/dL)
- 13 to < 16 years: 1.5 (male), 1.4 (female) maximum serum creatinine (mg/dL)
- >= 16 years: 1.7 (male), 1.4 (female) maximum serum creatinine (mg/dL)
- Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment)
- 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
- Patients with seizure disorder may be enrolled if seizures are well-controlled (i.e., patients must not have required rescue medications for uncontrolled seizures within 14 days prior to enrollment)
- Patients must be enrolled and protocol therapy must be projected to begin no later than 31 days after definitive surgery (Day 0). If a biopsy only was performed, the biopsy date will be considered the date of definitive surgery. For patients who have a biopsy or incomplete resection at diagnosis followed by additional surgery, the date of the last resection will be considered the date of definitive surgery
- All patients and/or their parents or legal guardians must sign a written informed consent
- All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Exclusion Criteria:
Patients with the following histologies:
- Diffuse astrocytoma (grade 2)
- Oligodendrogliomas (any grade)
- Pleomorphic xanthoastrocytoma (PXA, any grade)
- Patients with primary tumor location of brainstem or spinal cord
- Patients with M+ disease (defined as neuraxis dissemination either by imaging or by cytology)
- Patients with treatment-related acute myeloid leukemia (AML) (t-AML)/myelodysplastic syndrome (MDS) or with features suggestive of AML/MDS
- Prior allogenic bone marrow transplant or double umbilical cord blood transplantation
- Patients must not have received any prior tumor-directed therapy including radiation therapy, chemotherapy (tumor-directed therapy), molecularly targeted agents, or immunotherapy for the treatment of HGG other than surgical intervention and/or corticosteroids
Lumbar CSF cytology is not required, but may be performed if clinically indicated prior to study enrollment. If lumbar CSF cytology is positive, the patient is considered to have M+ disease and is ineligible
- Note: False positive cytology can occur within 10 days of surgery
- Patients with gliomatosis cerebri type 1 or 2
- Patients who are not able to receive protocol specified radiation therapy
- Patients must not be currently receiving other anti-cancer agents
- Patients with known constitutional mismatch repair deficiency syndrome (CMMR-D)/biallelic mismatch repair deficiency (bMMRD)
- Female patients who are pregnant are ineligible due to risks of fetal and teratogenic adverse events as seen in animal/human studies
- 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 an effective contraceptive method for the duration of their study participation and for 6 months after the last dose of protocol-specified chemotherapy
Sites / Locations
- Children's Hospital of Alabama
- USA Health Strada Patient Care Center
- Banner Children's at Desert
- Phoenix Childrens Hospital
- Arkansas Children's Hospital
- Kaiser Permanente Downey Medical Center
- Loma Linda University Medical Center
- Miller Children's and Women's Hospital Long Beach
- Children's Hospital Los Angeles
- Cedars Sinai Medical Center
- Mattel Children's Hospital UCLA
- Valley Children's Hospital
- UCSF Benioff Children's Hospital Oakland
- Kaiser Permanente-Oakland
- Children's Hospital of Orange County
- Lucile Packard Children's Hospital Stanford University
- Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
- Children's Hospital Colorado
- Connecticut Children's Medical Center
- Yale University
- Alfred I duPont Hospital for Children
- MedStar Georgetown University Hospital
- Children's National Medical Center
- Golisano Children's Hospital of Southwest Florida
- Memorial Regional Hospital/Joe DiMaggio Children's Hospital
- Nemours Children's Clinic-Jacksonville
- University of Miami Miller School of Medicine-Sylvester Cancer Center
- Nicklaus Children's Hospital
- AdventHealth Orlando
- Arnold Palmer Hospital for Children
- Nemours Children's Hospital
- Johns Hopkins All Children's Hospital
- Tampa General Hospital
- Saint Joseph's Hospital/Children's Hospital-Tampa
- Saint Mary's Hospital
- Children's Healthcare of Atlanta - Egleston
- Memorial Health University Medical Center
- Kapiolani Medical Center for Women and Children
- Saint Luke's Cancer Institute - Boise
- Lurie Children's Hospital-Chicago
- University of Illinois
- University of Chicago Comprehensive Cancer Center
- Loyola University Medical Center
- Saint Jude Midwest Affiliate
- Riley Hospital for Children
- Ascension Saint Vincent Indianapolis Hospital
- Blank Children's Hospital
- University of Iowa/Holden Comprehensive Cancer Center
- University of Kentucky/Markey Cancer Center
- Norton Children's Hospital
- Children's Hospital New Orleans
- Ochsner Medical Center Jefferson
- Eastern Maine Medical Center
- Johns Hopkins University/Sidney Kimmel Cancer Center
- Walter Reed National Military Medical Center
- Massachusetts General Hospital Cancer Center
- Dana-Farber Cancer Institute
- UMass Memorial Medical Center - University Campus
- C S Mott Children's Hospital
- Wayne State University/Karmanos Cancer Institute
- Ascension Saint John Hospital
- Helen DeVos Children's Hospital at Spectrum Health
- Bronson Methodist Hospital
- Beaumont Children's Hospital-Royal Oak
- Children's Hospitals and Clinics of Minnesota - Minneapolis
- University of Minnesota/Masonic Cancer Center
- Mayo Clinic in Rochester
- University of Mississippi Medical Center
- Children's Mercy Hospitals and Clinics
- Cardinal Glennon Children's Medical Center
- Washington University School of Medicine
- Mercy Hospital Saint Louis
- Children's Hospital and Medical Center of Omaha
- University of Nebraska Medical Center
- University Medical Center of Southern Nevada
- Sunrise Hospital and Medical Center
- Alliance for Childhood Diseases/Cure 4 the Kids Foundation
- Summerlin Hospital Medical Center
- Renown Regional Medical Center
- Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
- Morristown Medical Center
- Saint Peter's University Hospital
- Albany Medical Center
- Montefiore Medical Center - Moses Campus
- Roswell Park Cancer Institute
- Laura and Isaac Perlmutter Cancer Center at NYU Langone
- NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
- Memorial Sloan Kettering Cancer Center
- University of Rochester
- State University of New York Upstate Medical University
- New York Medical College
- Mission Hospital
- UNC Lineberger Comprehensive Cancer Center
- Carolinas Medical Center/Levine Cancer Institute
- Duke University Medical Center
- East Carolina University
- Wake Forest University Health Sciences
- Sanford Broadway Medical Center
- Children's Hospital Medical Center of Akron
- Cincinnati Children's Hospital Medical Center
- Rainbow Babies and Childrens Hospital
- Cleveland Clinic Foundation
- Nationwide Children's Hospital
- Dayton Children's Hospital
- ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
- University of Oklahoma Health Sciences Center
- Legacy Emanuel Children's Hospital
- Oregon Health and Science University
- Lehigh Valley Hospital-Cedar Crest
- Geisinger Medical Center
- Children's Hospital of Philadelphia
- Children's Hospital of Pittsburgh of UPMC
- Rhode Island Hospital
- Medical University of South Carolina
- Prisma Health Richland Hospital
- BI-LO Charities Children's Cancer Center
- Sanford USD Medical Center - Sioux Falls
- T C Thompson Children's Hospital
- East Tennessee Childrens Hospital
- Saint Jude Children's Research Hospital
- The Children's Hospital at TriStar Centennial
- Vanderbilt University/Ingram Cancer Center
- Dell Children's Medical Center of Central Texas
- Driscoll Children's Hospital
- Medical City Dallas Hospital
- UT Southwestern/Simmons Cancer Center-Dallas
- Cook Children's Medical Center
- Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
- M D Anderson Cancer Center
- Children's Hospital of San Antonio
- Methodist Children's Hospital of South Texas
- University of Texas Health Science Center at San Antonio
- Scott and White Memorial Hospital
- Primary Children's Hospital
- Children's Hospital of The King's Daughters
- Naval Medical Center - Portsmouth
- Virginia Commonwealth University/Massey Cancer Center
- Seattle Children's Hospital
- Providence Sacred Heart Medical Center and Children's Hospital
- Mary Bridge Children's Hospital and Health Center
- Madigan Army Medical Center
- West Virginia University Healthcare
- University of Wisconsin Carbone Cancer Center
- Marshfield Medical Center-Marshfield
- Children's Hospital of Wisconsin
- John Hunter Children's Hospital
- Sydney Children's Hospital
- The Children's Hospital at Westmead
- Queensland Children's Hospital
- Monash Medical Center-Clayton Campus
- Royal Children's Hospital
- Perth Children's Hospital
- Alberta Children's Hospital
- British Columbia Children's Hospital
- Janeway Child Health Centre
- IWK Health Centre
- McMaster Children's Hospital at Hamilton Health Sciences
- The Montreal Children's Hospital of the MUHC
- Centre Hospitalier Universitaire Sainte-Justine
- CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
- Starship Children's Hospital
- Christchurch Hospital
- HIMA San Pablo Oncologic Hospital
Arms of the Study
Arm 1
Experimental
Treatment (radiation therapy, veliparib, temozolomide)
CHEMORADIOTHERAPY PHASE: Patients receive veliparib PO BID and undergo 30 daily fractions of radiation therapy 5 days per week for 6-7 weeks in the absence of disease progression or unacceptable toxicity. MAINTENANCE CHEMOTHERAPY: Beginning 4 weeks after chemoradiotherapy phase, patients receive veliparib PO BID and temozolomide PO QD on days 1-5. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.