ABT-888, Radiation Therapy, and Temozolomide in Treating Patients With Newly Diagnosed Glioblastoma Multiforme
Condition: Brain and Central Nervous System Tumors
MeSH terms: Glioblastoma; Nervous System Neoplasms; Central Nervous System Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      RATIONALE: ABT-888 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. Drugs used in
      chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells,
      either by killing the cells or by stopping them from dividing. Giving ABT-888 together with
      radiation therapy and temozolomide may kill more tumor cells.

      PURPOSE: This phase I/II trial is studying the side effects and best dose of ABT-888 when
      given together with radiation therapy and temozolomide and to see how well it works in
      treating patients with newly diagnosed glioblastoma multiforme.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  To determine the maximum tolerated dose (MTD) of ABT-888 when administered in
           combination with radiotherapy and temozolomide in patients with newly diagnosed
           glioblastoma multiforme. (Phase I)

        -  To estimate the overall survival of patients treated with ABT-888 when administered at
           the MTD in combination with radiotherapy and temozolomide. (Phase II)

      Secondary

        -  To assess the toxicity associated with this regimen. (Phase I)

        -  To assess and describe the pharmacokinetics of ABT-888. (Phase I)

        -  To estimate the frequency of toxicity associated with this regimen. (Phase II)

      OUTLINE: This is a multicenter, phase I dose-escalation study of ABT-888 followed by a phase
      II study.

        -  Initiation therapy: Patients receive oral ABT-888 twice daily (once on day 1 only) and
           oral temozolomide once daily (beginning on day 2) in weeks 1-6. Patients enrolled in the
           phase I dose-escalation/phase II portion of the study also undergo concurrent
           radiotherapy once daily 5 days a week (beginning on day 2) in weeks 1-6. Treatment
           continues in the absence of disease progression or unacceptable toxicity.

        -  Maintenance therapy: Beginning 4 weeks after completion of initiation therapy, patients
           receive oral ABT-888 twice daily on days 1-7 and oral temozolomide once daily on days
           1-5. Treatment repeats every 28 days for up to 4 courses (6 courses for patients
           enrolled in the phase I dose-escalation/phase II portion of the study) in the absence of
           disease progression or unacceptable toxicity.

      Blood samples are collected periodically for pharmacokinetic, pharmacogenetic, and
      pharmacodynamic analysis. Samples are analyzed for concentration of ABT-888 in plasma by
      reversed-phase isocratic high performance liquid chromatography with electrospray ionization
      mass spectrometry; identification of novel markers of treatment response by plasma proteomic
      evaluation; DNA methylation and/or mutation; and PARP inhibition by ELISA.

      After completion of study therapy, patients are followed every 2 months.
    

Intervention name(s): temozolomide; veliparib; DNA methylation analysis; gene expression analysis; mutation analysis; proteomic profiling; high performance liquid chromatography; immunoenzyme technique; laboratory biomarker analysis; mass spectrometry; pharmacogenomic studies; pharmacological study; adjuvant therapy; radiation therapy
Intervention type(s): Drug; Drug; Genetic; Genetic; Genetic; Genetic; Other; Other; Other; Other; Other; Other; Procedure; Radiation
Intervention MeSH terms: Temozolomide; Veliparib
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: adult glioblastoma; adult gliosarcoma; adult giant cell glioblastoma