A Trial of the Protease Inhibitor Nelfinavir and Concurrent Radiation and Temozolomide in Patients With WHO Grade IV Glioma

Inclusion Criteria:

1. Patients > 18 years old.
2. Newly diagnosed and histologically confirmed supratentorial WHO Grade IV astrocytoma status-post maximally achievable resection.
3. ECOG performance status 0-2.
4. Absolute Neutrophil Count ≥ 1500 per mm3
5. Platelet count ≥ 100,000 per mm3
6. Serum creatinine < 1.5 times the upper limit of normal
7. Serum AST or ALT < 2 times the upper limit of normal
8. Serum bilirubin < 1.5 mg/dl
9. Patients who were receiving corticosteroids have to receive a stable or decreasing dose for at least 14 days before randomization.
10. No prior cranial radiotherapy will be permitted.
11. No known HIV infection.

12. The effects of NFV on the developing human fetus have been studied in HIV positive women.

    We do not, however, know the risks along with radiation. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

13. Patients must sign an informed consent document that indicates they are aware of the investigative nature of the treatment in this protocol as well as the potential risks and benefits.

Exclusion Criteria:

1. Prior cranial radiotherapy.
2. Patients may not be receiving or have received any other investigational agents during/or within 1 month prior to treatment with NFV.
3. Pregnant or lactating women.
4. Patients receiving the following drugs that are contraindicated with NFV will be excluded: antiarrhythmics (amiodarone, quinidine), antimycobacterial (rifampin), ergot derivatives (dihydroergotamine, ergonovine, ergotamine, methylergonovine), herbal products (St. John's wort), HMG-CoA reductase inhibitors (lovastatin, simvastatin), neuroleptic (pimozide), proton pump inhibitors, sedatives/hypnotics (midazolam, triazolam).
5. Patients receiving the following drugs will be clinically evaluated as to whether dosage/medication can be changed to permit patient on study: anti-convulsants (carbamazepine, phenobarbital, phenytoin), anti-mycobacterial (rifabutin), PDE5 inhibitors (sildenafil, vardenafil, tadalafil), HMG-CoA reductase inhibitor (atorvastatin, rosuvastatin), immunosuppressants (cyclosporine, tacrolimus, sirolimus), narcotic analgesic (methadone), oral contraceptive (ethinyl estradiol), macrolide antibiotic (azithromycin), antidepressant (trazadone).