Clinical Trial 18308

Cancer Type:
Interventions:Placebo; Temodal (Temozolomide); Temozolomide; Veliparib (ABT-888)

Study Type: Treatment
Phase of Study: Phase II/III

  • Peter Forsyth


Study Title

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


The purpose of this study is to find out if an investigational drug called veliparib can help people whose brain tumors show a change in a small region of DNA (gene).


Primary Objective: -Test whether the experimental combination of ABT-888 (veliparib) combined with TMZ, compared to the control of placebo combined with TMZ, significantly extends overall survival in newly diagnosed GBM patients with tumor MGMT promoter hypermethylation. Secondary Objectives: -Test whether the experimental treatment significantly extends progression-free survival. -Test whether the experimental treatment improves objective tumor response. -Test whether the experimental treatment is associated with significantly greater rates of grade 3 or higher adverse events. Correlative Science Objectives: -Evaluate the utility of dynamic susceptibility contrast (DSC) and diffusion weighted imaging (DWI) MRI techniques in defining time to progression in the setting of a large multi-institutional clinical trial. -Test the concordance between site-determined MGMT methylation status and central laboratory determination of MGMT status in cases with local testing. -Evaluate whether genetic or epigenetic alterations in DNA repair or replication genes are associated with overall survival, progression-free survival, and objective tumor response. -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.

Inclusion Criteria


  • Histologic documentation: newly diagnosed World Health Organization (WHO) grade IV intracranial glioblastoma or gliosarcoma; glioblastoma multiforme (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 O6-methylguanine methyltransferase (MGMT) methylation status evaluation
  • Tumor MGMT promoter hypermethylation determined by central testing
  • Confirmation by central pathology review of World Health Organization (WHO) grade IV glioblastoma or gliosarcoma
  • Absolute neutrophil count (ANC) >= 1500 cells/mm^3
  • Platelets >= 100,000 cells/mm^3
  • Creatinine => Bilirubin => Alanine aminotransferase (ALT) => Aspartate aminotransferase (AST) => Eastern Cooperative Oncology Group (ECOG) performance status => Measurable disease or non-measurable disease; extent of resection: patients with complete resection, partial resection, or biopsy are eligible
  • Progression: potential participants deemed to have progressive disease based on clinical deterioration after chemoradiation or radiographic progression outside of the radiation field are not eligible; potential participants deemed to have pseudoprogression are eligible
  • Must have completed standard radiotherapy and concomitant Temozolomide (TMZ) therapy as defined and determined by the study oncologist
  • Besides concomitant TMZ with radiation, no other therapy (neo-adjuvant or adjuvant) can be given prior to study registration, including chemotherapy, biologics, immunotherapy, radiation therapy, or Novo-TTF-100A System
  • Not pregnant and not nursing; females of childbearing potential must have negative urine or serum pregnancy test within 7 days of registration but before start of treatment
  • If receiving anticoagulation; should be on stable dose 2 weeks prior to registration

  • Exclusion Criteria


  • Seizure disorder that is uncontrolled at the time of registration; must be without seizures for at least 10 days prior to registration
  • Grade 3 or 4 thromboembolic disease within 6 months of registration
  • Known history of prolonged QT syndrome ((QT interval: The time from Q wave (of QRS complex) to the end of the T wave as it can be measured on an electrocardiogram; corresponds to ventricular systole.)
  • History of major surgery => Have had a local MGMT testing that is unmethylated