Clinical Trial Finder

Inclusion Criteria:

• - Histologically proven high grade glioma (WHO grade 3-4) which is progressive or recurrent following radiation therapy with or without chemotherapy.

• - Patients with previous low grade glioma who progressed after radiotherapy and chemotherapy and are biopsied and found to have a high grade glioma are eligible.

• - Patients must have recovered from toxicity of prior therapy - An interval of >= 3 months must have elapsed since the completion of the most recent course of radiation therapy.

• - Minimum interval since last drug therapy: 2 weeks since last non-cytotoxic therapy; 3 weeks must have elapsed since the completion of a non-nitrosourea containing chemotherapy regimen; 6 weeks since the completion of a nitrosourea containing chemotherapy regimen.

• - Patients must have a Karnofsky performance status >= 60% (i.e., must be able to care for himself/herself with the occasional help of others) - Patients must have normal hematologic, renal, and liver function (i.e., absolute neutrophil count >= 1500/mm^3, platelets >= 100,000/mm^3, HgB > 9 d/dl, creatinine =< 1.5mg/dl, total bilirubin =< 1.5mg/dl, transaminases =< 2.5 times the upper limits of the institutional norm) - Patients must be able to provide written informed consent.

• - Patients with the potential for pregnancy or impregnating their partner must agree to follow acceptable birth control methods to avoid contraception - Female patients of child-bearing potential must have a negative pregnancy test.

• - Patients must have no concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin of carcinoma in situ of the cervix and breast, adequately treated stage I or II cancer from which the patient is in complete remission.

• - Patients with other prior malignancies must be disease-free for >= 3 years.

• - Patients must be maintained on a stable corticosteroid regimen from the time of their baseline scan until the start of treatment.

• - Patients must have a Mini mental state exam score >= 15.

Exclusion Criteria:

• - Patients with serious concurrent infection or medical illness, which would jeopardize the ability of the patient to receive the treatment outlines in this protocol with reasonable safety.

• - Patients who are pregnant or breast-feeding.

• - Patients receiving concurrent therapy for their tumor (with the exception of steroids) - HIV positive.

• - Prior therapy with HIV protease inhibitors.

• - Concurrent therapy with hepatic enzyme inducing anticonvulsant.

• - Inability to be followed closely at the Cleveland Clinic.

- Patients requiring the use of medication well-known contraindicated for concomitant use with lopinavir/ritonavir: amiodarone, astemizole, bepridil, bupropione, cisapride, clorazepate, clozapim, diazepam, encainide, flecainide, flurazepam, meperidine, midazolam, primozide, piroxicam, propafenone, propoxifeno, quinidine, rifabutin, terfenadine, triazolam, zolpidem, dihydroergotamine, ergotamine

PRIMARY OBJECTIVES:

• I. To evaluate the 6-month progression-free survival in patients with recurrent or progressive high grade gliomas treated with ritonavir and lopinavir.

SECONDARY OBJECTIVES:

• I. To evaluate the toxicity of ritonavir and lopinavir in this patient population.

OUTLINE: Patients receive oral ritonavir and lopinavir twice daily in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed periodically.

Arms

Experimental: Arm I

Patients receive oral ritonavir and lopinavir twice daily in the absence of disease progression or unacceptable toxicity.

Interventions

Drug: - ritonavir

Given orally

Drug: - lopinavir

Given orally