Ritonavir and Lopinavir in Treating Patients With Progressive or Recurrent High-Grade Glioma

Study Overview
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Brief Summary
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RATIONALE: Ritonavir and lopinavir may stop the growth of gliomas by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. PURPOSE: This phase II trial is studying how well giving ritonavir together with lopinavir works in treating patients with progressive or recurrent high-grade glioma.

Detailed Description
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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.

Official Title
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Phase II Trial of Ritonavir/Lopinavir in Patients With Progressive of Recurrent High-Grade Gliomas

Conditions
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Brain Tumor, Anaplastic Astrocytoma, Anaplastic Ependymoma, Anaplastic Oligodendroglioma, Brain Stem Glioma, Giant Cell Glioblastoma, Glioblastoma, Gliosarcoma, Mixed Glioma

Intervention / Treatment
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* Drug: ritonavir
* Drug: lopinavir


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients receive oral ritonavir and lopinavir twice daily in the absence of disease progression or unacceptable toxicity. | Drug: ritonavir<br>* Given orally<br>* Other names: RIT;Drug: lopinavir<br>* Given orally<br>* Other names: ABT-378/r;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | Number of patients that remained disease free at 6 months from start of treatment. | At 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Grade 3-5 Toxicity as Assessed by NCI CTC v3.0 | Number of participants with adverse events grades 3-5. For a detailed list of adverse events see the adverse event module. | at 6 months from start of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adult brain tumor, adult anaplastic astrocytoma, adult anaplastic ependymoma, adult anaplastic oligodendroglioma, adult brain stem glioma, adult giant cell glioblastoma, adult glioblastoma, adult gliosarcoma, adult mixed glioma, recurrent adult brain tumor