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 BRAFV600 Mutations
概览
- 阶段
- 2 期
- 干预措施
- Radiation Therapy
- 疾病 / 适应症
- Anaplastic Astrocytoma
- 发起方
- National Cancer Institute (NCI)
- 入组人数
- 38
- 试验地点
- 317
- 主要终点
- Event Free Survival (EFS)
- 状态
- 进行中（未招募）
- 最后更新
- 19天前
概览
简要总结
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.
详细描述
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.
研究者
入排标准
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Radiation Therapy
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.
干预措施: Temozolomide
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.
干预措施: Veliparib
结局指标
主要结局
Event Free Survival (EFS)
时间窗: Up to 2 years
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.
次要结局
- Objective Response(Anytime during treatment (up to 1 year from enrollment))
- Overall Survival (OS)(Up to 2 years)