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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.
Full 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.
Enrollment
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Inclusion and exclusion criteria
DISEASE CHARACTERISTICS:
Histologically confirmed diagnosis of 1 of the following:
Patients whose original histology was low-grade glioma are eligible provided they were subsequently diagnosed with glioblastoma or gliosarcoma
Unequivocal radiographic evidence for tumor progression by MRI within 14 days prior to registration and with a stable or decreasing dose of steroids at least 5 days prior to scanning OR recent resection (registration within 30 days of resection) as long as all of the following conditions are met:
No evidence of acute (i.e., new and active) intratumoral hemorrhage on MRI
PATIENT CHARACTERISTICS:
Karnofsky performance status 70-100%
White blood cell (WBC) count ≥ 3,000/mm^3
Absolute neutrophil count (ANC) ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Hemoglobin ≥ 10.0 g/dL (transfusion or other intervention allowed)
Serum glutamic oxaloacetic transaminase (SGOT) ≤ 3.0 times upper limit of normal (ULN)
Serum glutamic pyruvic transaminase (SGPT) ≤ 3.0 times ULN
Bilirubin ≤ 1.25 times ULN
Creatinine < 1.7 mg/dL OR estimated glomerular filtration rate (GFR) ≥ 30 mL/min
Urine protein:creatinine ratio ≤ 0.5 OR urine protein < 1,000 mg by 24-hour urine collection**
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for ≥ 6 months after completion of study therapy
Able to undergo brain MRI scans with IV gadolinium
Able to swallow oral medications
Patients with a history of seizure, or new onset of seizures, should be clinically controlled with no seizures for at least 14 days prior to registration
No other prior invasive malignancy (except for nonmelanomatous skin cancer or carcinoma in situ of the cervix) unless the patient has been disease-free and off therapy for that disease for ≥ 3 years
No severe, active comorbidity, including any of the following:
No condition that would impair the ability to swallow pills (e.g., GI tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease)
No disease that would obscure toxicity or dangerously alter drug metabolism
Not on dialysis
No history of chronic hepatitis B or C Note: **Required for patients who received prior bevacizumab and developed known clinically significant nephrotic syndrome during treatment and whose baseline values have not returned to normal.
PRIOR CONCURRENT THERAPY:
Primary purpose
Allocation
Interventional model
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257 participants in 8 patient groups
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Data sourced from clinicaltrials.gov
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