A Phase I Study of Bortezomib and Temozolomide in Patients With Refractory Solid Tumors

Inclusion 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