Ritonavir and Lopinavir in Treating Patients With Progressive or Recurrent High-Grade Glioma
Condition: Brain Tumor; Anaplastic Astrocytoma; Anaplastic Ependymoma; Anaplastic Oligodendroglioma; Brain Stem Glioma; Giant Cell Glioblastoma; Glioblastoma; Gliosarcoma; Mixed Glioma
MeSH terms: Glioblastoma; Glioma; Brain Neoplasms; Astrocytoma; Ependymoma; Gliosarcoma; Oligodendroglioma
Intervention: ritonavir; lopinavir
Intervention description: Given orally; Given orally
Intervention MeSH terms: Ritonavir; Lopinavir
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 19.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: 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

Summary:

      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.
    

Eligibility criteria:

        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