NCT02152982

Temozolomide With or Without Veliparib in Treating Patients With Newly Diagnosed Glioblastoma Multiforme

A Phase II/III Randomized Trial of Veliparib or Placebo in Combination With Adjuvant Temozolomide in Newly Diagnosed Glioblastoma With MGMT Promoter Hypermethylation

• Status: Active Not Recruiting
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 447 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Glioblastoma
• Gliosarcoma

Interventions

Type	Name	Description
OTHER	Laboratory Biomarker Analysis	Correlative studies
OTHER	Placebo Administration	Given PO
OTHER	Quality-of-Life Assessment	Ancillary studies
DRUG	Temozolomide	Given PO
DRUG	Veliparib	Given PO

Timeline

• Start date: 2014-12-15
• Primary completion: 2021-12-01
• Completion: 2026-12-26
• First posted: 2014-06-02
• Last updated: 2026-04-13
• Results posted: 2023-04-04

Locations

392 sites across 2 countries: United States, Puerto Rico