A Phase 2 Study of Veliparib (ABT-888) and Local Irradiation, Followed by Maintenance Veliparib and Temozolomide, in Patients With Newly Diagnosed High-Grade Glioma (HGG) Without H3 K27M or BRAFV600E Mutations
Sandeep Batra, MD
Primary Investigator
Brief description of study
This phase II trial studies how well veliparib, radiation therapy, and temozolomide work in treating participants with newly diagnosed malignant glioma without H3 K27M or BRAFV600E mutations.
Detailed description of study
Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. 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 participants with newly diagnosed malignant glioma without H3 K27M or BRAFV600E mutations.
Eligibility of study
You may be eligible for this study if you meet the following criteria:
- Conditions: Anaplastic Astrocytoma, Glioblastoma, Malignant Glioma
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Age: Between 3 Years - 25 Years
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Gender: All
Inclusion Criteria
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 BRAFV600E 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.
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 diagnostic surgery (Day 0)
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 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
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 4 months after the last dose of veliparib
