Bortezomib and Temozolomide in Treating Patients With Brain Tumors or Other Solid Tumors That Have Not Responded to Treatment
Brain and Central Nervous System Tumors, Lymphoma, Metastatic Cancer
About this trial
This is an interventional treatment trial for Brain and Central Nervous System Tumors focused on measuring adult glioblastoma, adult anaplastic astrocytoma, adult giant cell glioblastoma, recurrent adult brain tumor, adult gliosarcoma, adult mixed glioma, adult anaplastic oligodendroglioma, primary central nervous system lymphoma, adult diffuse astrocytoma, adult brain stem glioma, adult central nervous system germ cell tumor, adult choroid plexus tumor, adult craniopharyngioma, adult ependymoblastoma, adult medulloblastoma, adult supratentorial primitive neuroectodermal tumor (PNET), adult anaplastic ependymoma, adult ependymoma, adult myxopapillary ependymoma, adult subependymoma, adult anaplastic meningioma, adult melanocytic lesion, adult meningeal hemangiopericytoma, adult grade I meningioma, adult grade II meningioma, adult grade III meningioma, adult papillary meningioma, adult oligodendroglioma, adult pineoblastoma, adult pineocytoma, tumors metastatic to brain, unspecified adult solid tumor, protocol specific, adult pilocytic astrocytoma, adult subependymal giant cell astrocytoma
Eligibility Criteria
DISEASE CHARACTERISTICS:
Histologically or cytologically confirmed solid tumors including the following
- Recurrent high-grade glioma
- Recurrent metastatic brain tumors
- Recurrent primary brain tumor including primary CNS lymphoma
- Other refractory solid tumors
- Unresectable disease for which standard curative or palliative measures do not exist or are no longer effective
- Measurable or nonmeasurable disease
PATIENT CHARACTERISTICS:
Inclusion criteria:
- Karnofsky performance status 60-100%
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Serum creatinine ≤ 1.5 x upper limit of normal (ULN)
- Total bilirubin ≤ 2.0 mg/dL
- AST ≤ 4.0 x ULN
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Patient must be able to understand and is willing to sign a written informed consent document
Exclusion criteria:
Any of the following conditions:
- Myocardial infarction within the past 6 months or New York Heart Association class III or IV heart failure
- Uncontrolled angina
- Severe uncontrolled ventricular arrhythmias
ECG evidence of acute ischemia or active conduction system abnormalities
- Any ECG abnormalities prior to study entry must be documented by the investigator as not medically relevant
- Serious medical or psychiatric illness that would, in the opinion of the investigator, potentially interfere with the completion of treatment
- History of sensitivity to boron or mannitol
PRIOR CONCURRENT THERAPY:
Inclusion criteria:
- At least 4 weeks since prior chemotherapy (6 weeks for nitrosourea-containing chemotherapy), immunotherapy, or radiotherapy and recovered
- More than 10 days since prior anticonvulsant drugs that induce hepatic metabolic enzymes for patients in group A
Recovered from major surgery
- Corticosteroids for cerebral edema allowed provided the patient is on a stable dose for at least 1 week
Exclusion criteria:
- Patients enrolled on another clinical trial
- HIV-positive patients on antiretroviral therapy
- Concurrent chemotherapy or radiotherapy
- Patient requires anti-seizure medication but is not on a stable dose and agent of anti-seizure medication
Sites / Locations
- City of Hope Comprehensive Cancer Center
- City of Hope Medical Group
Arms of the Study
Arm 1
Experimental
Treatment (temozolomide, bortezomib)
GROUP A: Patients receive oral temozolomide once a day on days 1-5 and bortezomib IV on days 2, 5, 9, and 12. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. GROUP B: Patients receive temozolomide and bortezomib as in group A. Cohorts of patients in both groups receive escalating doses of both study drugs until the maximum tolerated doses are determined. All patients undergo blood sample collection periodically for pharmacokinetic studies. Samples are analyzed for bortezomib concentration (groups A and B) and trough levels of anticonvulsants (group A only).