Presurgery Bortezomib for Recurrent Malignant Gliomas Followed by Postop Bortezomib & Temozolomide
Presurgery Bortezomib for Recurrent Malignant Gliomas Followed by Postop Bortezomib & Temozolomide
Bortezomib 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
 bortezomib before surgery may make the tumor smaller and reduce the amount of normal tissue
 that needs to be removed. Giving bortezomib together with temozolomide after surgery may kill
 any tumor cells that remain after surgery.

 This phase II trial is studying how well giving bortezomib before surgery followed by giving
 bortezomib together with temozolomide after surgery works in treating patients with recurrent
 malignant glioma.
Patients receive bortezomib IV on days 1, 4, and 8. Patients then undergo surgical resection
 of the tumor on day 8 or 9.

 Beginning approximately 14 days after surgery, patients receive oral temozolomide on days 1-7
 and 14-21 and bortezomib IV on days 7 and 21. Treatment repeats every 28 days for up to 2
 years in the absence of disease progression or unacceptable toxicity.

 Tumor tissue and blood samples are collected periodically for biomarker analysis, gene
 methylation studies, and pharmacokinetic studies.

 After completion of study therapy, patients are followed up every 3 months for 2 years.
Inclusion Criteria:

 -  Histologically confirmed malignant glioma, including any of the following subtypes:

 -  Glioblastoma multiforme

 -  Gliosarcoma

 -  Anaplastic astrocytoma

 -  Anaplastic oligodendroglioma

 -  Anaplastic mixed oligoastrocytoma

 -  Malignant astrocytoma not otherwise specified

 -  Must show unequivocal evidence of tumor recurrence or progression by MRI or CT scan
 with contrast

 -  Candidate for surgery AND requires surgery

 -  Evaluable or measurable disease following resection of recurrent tumor is not
 required

 -  Failed prior standard radiotherapy and temozolomide

 -  Patients who have undergone stereotactic radiosurgery must have confirmation of
 true progressive disease (rather than radiation necrosis) by PET scan, magnetic
 resonance spectroscopy (MRS), or magnetic resonance perfusion (MRP) prior to
 surgery

 -  Patients with lower-grade gliomas that have undergone radiographic malignant
 transformation allowed provided they failed radiotherapy (with or without
 temozolomide) and require surgery

 -  Life expectancy > 12 weeks

 Exclusion Criteria:

 -  Not pregnant or nursing

 -  Negative pregnancy test

 -  No other medical issues (e.g., bleeding, infection, HIV, or serious medical or
 psychiatric illness) that would preclude study therapy

 -  Myocardial infarction within the past 6 months

 -  No other active cancer(s) except non-melanoma skin cancer or carcinoma in situ of the
 cervix, unless in complete remission and off of all therapy for that cancer for ≥ 3
 years

 -  No hypersensitivity to bortezomib, boron, or mannitol

 -  More than 4 weeks since prior radiotherapy

 -  At least 4 weeks since prior cytotoxic therapy (6 weeks for nitrosoureas)

 -  At least 3 weeks since prior investigational drugs

 -  At least 2 weeks since prior enzyme-inducing anticonvulsants

 -  Concurrent non-enzyme-inducing anticonvulsants allowed

 -  No other concurrent standard or investigational anticancer treatment