A Phase II/III Randomized Trial of Veliparib or Placebo in Combination With Adjuvant Temozolomide in Newly Diagnosed Glioblastoma With MGMT Promoter Hypermethylation
概览
- 阶段
- 2 期
- 干预措施
- Veliparib
- 疾病 / 适应症
- Glioblastoma
- 发起方
- National Cancer Institute (NCI)
- 入组人数
- 447
- 试验地点
- 706
- 主要终点
- Overall Survival (OS)
- 状态
- 进行中（未招募）
- 最后更新
- 4天前
概览
简要总结
This randomized phase II/III trial studies how well temozolomide and veliparib work compared to temozolomide alone in treating patients with newly diagnosed glioblastoma multiforme. 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. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether temozolomide is more effective with or without veliparib in treating glioblastoma multiforme.
详细描述
PRIMARY OBJECTIVE: I. Test whether the experimental combination of ABT-888 (veliparib) combined with TMZ (temozolomide), compared to the control of placebo combined with TMZ, significantly extends overall survival in newly diagnosed glioblastoma multiforme (GBM) patients with tumor MGMT promoter hypermethylation. SECONDARY OBJECTIVES: I. Test whether the experimental treatment significantly extends progression-free survival. II. Test whether the experimental treatment improves objective tumor response. III. Test whether the experimental treatment is associated with significantly greater rates of grade 3 or higher adverse events. CORRELATIVE SCIENCE OBJECTIVES: I. Evaluate the utility of dynamic susceptibility contrast (DSC) and diffusion weighted imaging (DWI) magnetic resonance imaging (MRI) techniques in defining time to progression in the setting of a large multi-institutional clinical trial. II. Test the concordance between site-determined MGMT methylation status and central laboratory determination of MGMT status in cases with local testing. III. Evaluate whether genetic or epigenetic alterations in deoxyribonucleic acid (DNA) repair or replication genes are associated with overall survival, progression-free survival, and objective tumor response. IV. Test whether polymorphisms in MGMT, PARP1, or other DNA repair proteins, are associated with overall survival, progression-free survival, objective tumor response, or rates of grade 3 or higher adverse events. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive temozolomide orally (PO) once daily (QD) on days 1-5 and placebo PO twice daily (BID) on days 1-7. Treatment repeats every 28 days for 6 cycles in the absence of disease progression (confirmed progression) or unacceptable toxicity. ARM II: Patients receive temozolomide as in Arm I and veliparib PO BID on days 1-7. Treatment repeats every 28 days for 6 cycles in the absence of disease progression (confirmed progression) or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 3 years, every 6 months for 2 years.
研究者
入排标准
入选标准
- •Histologic documentation: newly diagnosed World Health Organization (WHO) grade IV intracranial glioblastoma or gliosarcoma; GBM with oligodendroglial features are NOT PERMITTED in this study if they are 1p19q codeleted; sites submitting GBM with oligodendroglial features will be asked to provide results of 1p/19q codeletion status
- •Sufficient tissue available for central pathology review and MGMT methylation status evaluation
- •Patients who have had a local MGMT testing that is unmethylated are not allowed to participate
- •Tumor MGMT promoter hypermethylation determined by central testing at MD Anderson
- •Confirmation by central pathology review of WHO grade IV glioblastoma or gliosarcoma
- •Absolute neutrophil count (ANC) \>= 1500 cells/mm\^3 (within 14 days prior to study registration)
- •Platelets \>= 100,000 cells/mm\^3 (within 14 days prior to study registration)
- •Creatinine =\< 1.5 x upper limit of normal (ULN) (within 14 days prior to study registration)
- •Bilirubin =\< 1.5 x ULN (within 14 days prior to study registration; unless patient has Gilbert's disease)
- •Alanine aminotransferase (ALT) =\< 3 x ULN (within 14 days prior to study registration)
排除标准
- 未提供
研究组 & 干预措施
Arm I (temozolomide, placebo)
Patients receive temozolomide PO QD on days 1-5 and placebo PO BID on days 1-7. Treatment repeats every 28 days for 6 cycles in the absence of disease progression (confirmed progression) or unacceptable toxicity.
干预措施: Veliparib
Arm II (temozolomide, veliparib)
Patients receive temozolomide as in Arm I and veliparib PO BID on days 1-7. Treatment repeats every 28 days for 6 cycles in the absence of disease progression (confirmed progression) or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis
Arm I (temozolomide, placebo)
Patients receive temozolomide PO QD on days 1-5 and placebo PO BID on days 1-7. Treatment repeats every 28 days for 6 cycles in the absence of disease progression (confirmed progression) or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis
Arm I (temozolomide, placebo)
Patients receive temozolomide PO QD on days 1-5 and placebo PO BID on days 1-7. Treatment repeats every 28 days for 6 cycles in the absence of disease progression (confirmed progression) or unacceptable toxicity.
干预措施: Placebo Administration
Arm I (temozolomide, placebo)
Patients receive temozolomide PO QD on days 1-5 and placebo PO BID on days 1-7. Treatment repeats every 28 days for 6 cycles in the absence of disease progression (confirmed progression) or unacceptable toxicity.
干预措施: Quality-of-Life Assessment
Arm II (temozolomide, veliparib)
Patients receive temozolomide as in Arm I and veliparib PO BID on days 1-7. Treatment repeats every 28 days for 6 cycles in the absence of disease progression (confirmed progression) or unacceptable toxicity.
干预措施: Quality-of-Life Assessment
Arm II (temozolomide, veliparib)
Patients receive temozolomide as in Arm I and veliparib PO BID on days 1-7. Treatment repeats every 28 days for 6 cycles in the absence of disease progression (confirmed progression) or unacceptable toxicity.
干预措施: Temozolomide
Arm I (temozolomide, placebo)
Patients receive temozolomide PO QD on days 1-5 and placebo PO BID on days 1-7. Treatment repeats every 28 days for 6 cycles in the absence of disease progression (confirmed progression) or unacceptable toxicity.
干预措施: Temozolomide
Arm II (temozolomide, veliparib)
Patients receive temozolomide as in Arm I and veliparib PO BID on days 1-7. Treatment repeats every 28 days for 6 cycles in the absence of disease progression (confirmed progression) or unacceptable toxicity.
干预措施: Veliparib
结局指标
主要结局
Overall Survival (OS)
时间窗: 83 months
The distribution of OS for each arm will be estimated using the Kaplan-Meier method and compared with a stratified logrank test.
次要结局
- Objective Tumor Response(5 years)
- Overall Adverse Event Rates for Grade 3 or Higher Adverse Events(5 years)
- Interaction With Optune Device(10 years)
- Progression-free Survival (PFS)(120 months)
- Objective Tumor Response(5 years)
- Overall Adverse Event Rates for Grade 3 or Higher Adverse Events(5 years)