This phase II trial studies how well veliparib, radiation therapy, and temozolomide work in treating patients with newly diagnosed malignant glioma without H3 K27M or BRAFV600 mutations. Poly adenosine diphosphate (ADP) ribose polymerases (PARPs) are proteins that help repair DNA mutations. PARP inhibitors, such as veliparib, can keep PARP from working, so tumor cells can't repair themselves, and they may stop growing. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving veliparib, radiation therapy, and temozolomide may work better in treating patients with newly diagnosed malignant glioma without H3 K27M or BRAFV600 mutations compared to radiation therapy and temozolomide alone.
PRIMARY OBJECTIVES: I. To determine whether veliparib (ABT-888), when added to radiotherapy (RT) and temozolomide, is efficacious for the treatment of patients with newly-diagnosed high-grade glioma (HGG) whose tumors' molecular profile are wild-type for H3 K27M, BRAF, and IDH1/2. II. To determine whether veliparib (ABT-888), when added to RT and temozolomide, is efficacious for the treatment of patients with newly-diagnosed HGG whose tumors' molecular profile are wild-type for H3 K27M and BRAF and harbor an IDH1/2 mutation. EXPLORATORY OBJECTIVES: I. To explore associations of genomic, transcriptomic, and/or epigenetic alterations of the tumors with treatment response and outcome. II. To explore the extent to which patients with BRCA1/2 gene alterations and other deoxyribonucleic acid (DNA) damaged genes display tumor genomic features consistent with homologous repair deficiency (HRD), including large scale state transitions (LSTs), mutational signature 3, and an enrichment for deletions flanked by sequences of (micro) homology. III. To explore the burden of high, moderate, and low penetrant germline alterations in HRD genes (such as BRCA1, BRCA2, PALB2, Fanconi complex genes, ATM, CHEK2, RAD51B/C/D), mis-match repair genes (such as MLH1, MSH2, MSH6, PMS2, EPCAM), and energy metabolism genes (such as SDHA, SDHB, SDHC, SDHAF2, SDHD, IDH1, IDH2, and FH). IV. To explore constitutional imprinting abnormalities associated with EP300 and IGF2 in peripheral blood from patients with HGGs. OUTLINE: CHEMORADIOTHERAPY PHASE: Patients receive veliparib orally (PO) twice daily (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 once daily (QD) on days 1-5. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for year 1, every 4 months for year 2, every 6 months for year 3, and then once yearly for years 4-10.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
38
Children's Hospital of Alabama
Birmingham, Alabama, United States
USA Health Strada Patient Care Center
Mobile, Alabama, United States
Banner Children's at Desert
Mesa, Arizona, United States
Phoenix Childrens Hospital
Phoenix, Arizona, United States
Arkansas Children's Hospital
Little Rock, Arkansas, United States
Event Free Survival (EFS)
Compare event free survival to historical data for each stratum. Analysis will be based on a 2-sample, 1 sided logrank test. EFS is measured from time of enrollment to the date of first documented progression, second malignancy, or date of death from any cause, whichever comes first. Subjects who do not have any event will be censored at the last follow-up date.
Time frame: Up to 2 years
Objective Response
Estimate the objective response rate in patients with measurable disease. The 95% confidence interval will be calculated by Clopper-Pearson method. Objective responses are defined as patients who achieved complete response or partial response anytime during treatment. Tumor response criteria are determined by changes in size using the longest tumor dimension, and its perpendicular. Either T1, T2 weighted/FLAIR images are used - whichever gives the best estimate of tumor size. Complete Response (CR): Disappearance of all target lesions; Partial response (PR): \>=50% decrease in the sum of the products of the two perpendicular diameters of target lesions, compared to baseline measurement. Objective Response = CR + PR.
Time frame: Anytime during treatment (up to 1 year from enrollment)
Overall Survival (OS)
The Kaplan-Meier method will be used to estimate the 2-year overall survival for each stratum. OS is measured from time of enrollment to the date of death from any cause. Subjects who do not have any event will be censored at the last follow-up date.
Time frame: Up to 2 years
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Kaiser Permanente Downey Medical Center
Downey, California, United States
Loma Linda University Medical Center
Loma Linda, California, United States
Miller Children's and Women's Hospital Long Beach
Long Beach, California, United States
Children's Hospital Los Angeles
Los Angeles, California, United States
Cedars Sinai Medical Center
Los Angeles, California, United States
...and 153 more locations