Veliparib and Temozolomide in Treating Patients With Recurrent Glioblastoma

DISEASE CHARACTERISTICS:

• Histologically confirmed diagnosis of 1 of the following:

  • Any intracranial high-grade glioma (phase I*)
  • Glioblastoma or gliosarcoma (phase II*)
• 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:

  • Patients must have recovered from the effects of surgery
  • Residual disease following resection of recurrent glioblastoma is not mandated for eligibility into the study; to best assess the extent of residual disease post-operatively, a post-operative MRI scan should be performed within 28 days prior to registration and within 96 hours post surgery (although 24 hours would be optimum)
  • Prior radiation is required for the phase I* arm
  • Patients must have completed a course of radiation therapy and at least 2 consecutive adjuvant cycles of temozolomide (phase II*)
  • A stable or decreasing dose of steroids at least 5 days prior to scanning is not mandated for patients who had a recent resection

• No evidence of acute (i.e., new and active) intratumoral hemorrhage on MRI

  • Patients with MRI demonstrating old hemorrhage or subacute blood after a neurosurgical procedure (biopsy or resection) are eligible NOTE: *Phase I was closed and phase II was opened on 3/6/12.

PATIENT CHARACTERISTICS:

• Karnofsky performance status 70-100%
• WBC ≥ 3,000/mm^3
• ANC ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 10.0 g/dL (transfusion or other intervention allowed)
• SGOT ≤ 3.0 times upper limit of normal (ULN)
• SGPT ≤ 3.0 times ULN
• Bilirubin ≤ 1.25 times ULN
• Creatinine < 1.7 mg/dL OR estimated 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:

  • Transmural myocardial infarction or unstable angina within the past 6 months
  • Evidence of recent myocardial infarction or ischemia as indicated by S-T elevations of ≥ 2 mm on EKG performed within the past 14 days
  • NYHA class II-IV congestive heart failure requiring hospitalization within the past 12 months
  • Stroke or transient ischemic attack within the past 6 months
  • Cerebral vascular accident within the past 6 months
  • Serious and inadequately controlled cardiac arrhythmia
  • Clinically significant peripheral vascular disease
  • Evidence of bleeding diathesis or coagulopathy
  • Serious non-healing would, ulcer, or bone fracture
  • Abdominal fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess within the past 28 days
  • Significant traumatic injury within the past 28 days
  • Acute bacterial or fungal infection requiring IV antibiotics at the time of study registration
  • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within the past 14 days
  • AIDS based upon current CDC definition (HIV testing is not required)
• 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:

• See Disease Characteristics
• Recovered from the toxic effects of prior therapy
• Prior interstitial brachytherapy, Gliadel wafer, or stereotactic radiosurgery allowed provided there is confirmation of progressive disease by PET scan, thallium scan, MRI spectroscopy, perfusion MRI, or surgical documentation
• No more than 3 prior treatment regimens (phase I*)
• No more than 2 prior treatment regimens for recurrent glioblastoma/gliosarcoma (phase II*)
• More than 28 days since prior major surgical procedure or open biopsy (with the exception of craniotomy)
• At least 28 days since prior investigational agents or cytotoxic agents (42 days for nitrosoureas, 21 days for procarbazine, and 14 days for vincristine)
• At least 14 days since prior non-cytotoxic agents (e.g., bevacizumab, interferon, tamoxifen, thalidomide, isotretinoin, or tyrosine kinase inhibitors)
• No concurrent highly-active antiretroviral therapy
• No concurrent herbal products of unknown constitution
• No concurrent major surgical procedures NOTE: *Phase I was closed and phase II was opened on 3/6/12.