Clinical trial NCT01026493
Conditions: Brain and Central Nervous System Tumors
Keywords: adult giant cell glioblastoma adult glioblastoma adult gliosarcoma recurrent adult brain tumor adult anaplastic astrocytoma adult anaplastic ependymoma adult anaplastic oligodendroglioma adult brain stem glioma adult mixed glioma adult pineal gland astrocytoma
Sponsor: Radiation Therapy Oncology Group
Start date: 2010-07-01; Completion date: 2016-12-01
Enrollment: 257 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
RATIONALE: Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. 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 veliparib together with temozolomide may kill more tumor cells.

PURPOSE: This randomized phase I/II trial is studying the side effects and best dose of giving veliparib together with temozolomide and to see how well it works in treating patients with recurrent glioblastoma.

Detailed description:
OBJECTIVES:

Primary

* To define the maximum-tolerated dose of the combination of temozolomide and veliparib in patients with recurrent glioblastoma previously or not treated with temozolomide. (Phase I\*)
* To determine the efficacy of the combination of temozolomide and veliparib (using a 5-day vs 21-day schedule) as measured by the 6-month progression-free survival rate in patients with recurrent glioblastoma previously treated with temozolomide. (Phase II\*)

Secondary

* To characterize the safety profile of the combination of temozolomide and veliparib. (Phase I\*)
* To determine the adverse event profile and tolerability of the combination of temozolomide and veliparib (using a 5-day vs 21-day schedule) in patients with recurrent glioblastoma. (Phase II\*)
* To determine the efficacy of the combination of temozolomide and veliparib (using a 5-day vs 21-day schedule) as measured by objective response in patients with measurable disease. (Phase II\*)
* To determine the overall survival of patients treated with the combination of temozolomide and veliparib (using a 5-day vs 21-day schedule). (Phase II\*) Note: \*Phase I was closed and phase II was opened on 3/6/12.

OUTLINE: This is a multicenter, phase I\* dose-escalation study followed by a phase II\* randomized study. Patients enrolled in the phase II portion are stratified according to bevacizumab (BEV) status (bevacizumab-naive vs bevacizumab-failure), age (\< 50 years vs ≥ 50 years), Karnofsky performance status (70-80% vs 90-100%), and recent resection (yes vs no/biopsy only).

* Phase I:\* Patients receive oral temozolomide once daily and oral veliparib twice daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
* Phase II:\* Patients are randomized to 1 of 2 treatment arms.

  * Arm I: Patients receive temozolomide and veliparib as in phase I.
  * Arm II: Patients receive oral temozolomide once daily and oral veliparib twice daily on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 12 weeks for 1 year, every 26 weeks for 2 years, and then annually thereafter.

Note: \*Phase I was closed and phase II was opened on 3/6/12.

PROJECTED ACCRUAL: A total of 240 patients (28 for phase I\* and 212 for phase II\*) will be accrued for this study.

Arms: arm 1: ABT-888 20 mg x 21 days plus temozolomide 60 mg x 21 days arm 2: ABT-888 40 mg x 21 days plus temozolomide 60 mg x 21 days arm 3: ABT-888 20 mg x 21 days plus temozolomide 75 mg x 21 days arm 4: ABT-888 40 mg x 21 days plus temozolomide 75 mg x 21 days arm 5: ABT-888 40 mg x 21 days plus temozolomide 75 mg x 21 days arm 6: ABT-888 40 mg x 5 days plus temozolomide 150 mg x 5 days arm 7: ABT-888 40 mg x 21 days plus temozolomide 75 mg x 21 days arm 8: ABT-888 40 mg x 5 days plus temozolomide 150 mg x 5 days
Interventions: intervention 1: temozolomide 60 mg x 21 days intervention 2: temozolomide 75 mg x 21 days intervention 3: ABT-888 20 mg x 21 days intervention 4: ABT-888 40 mg x 21 days intervention 5: Temozolomide 150 mg x 5 days intervention 6: ABT-888 40 mg x 5 days
Intervention descriptions: intervention 1: Temozolomide 60 mg/m2 x 21 days, with a 28-day cycle. Treatment will continue until progressive disease unless toxicity or the discretion of the treating physician precludes further therapy. intervention 2: Temozolomide 75 mg/m2 x 21 days, with a 28-day cycle. Treatment will continue until progressive disease unless toxicity or the discretion of the treating physician precludes further therapy. intervention 3: 20 mg bid x 21 days, with a 28-day cycle. Treatment will continue until progressive disease unless toxicity or the discretion of the treating physician precludes further therapy. intervention 4: 40 mg bid x 21 days/28-day cycle. Treatment continues until progressive disease unless toxicity or the discretion of the treating physician preclude further therapy intervention 5: 150 mg/m2 x 5 days (up to 200 mg/m2 after 2nd cycle)\*, with a 28-day cycle; dose reduction to 125 mg/m2 if necessary. Treatment continues until progressive disease unless toxicity or the discretion of the treating physician preclude intervention 6: 40 mg bid x 5 days/28-day cycle. Treatment continues until progressive disease unless toxicity or the discretion of the treating physician preclude

Protocol documents: