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

Phase 2

Terminated

• Conditions: Brain Tumor; Anaplastic Astrocytoma; Anaplastic Ependymoma; Anaplastic Oligodendroglioma; Brain Stem Glioma; Giant Cell Glioblastoma; Glioblastoma; Gliosarcoma; Mixed Glioma
• Interventions: Drug: ritonavir; Drug: lopinavir

• Registration Number: NCT01095094
• Lead Sponsor: Case Comprehensive Cancer Center

Brief 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.

Detailed Description

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.

Study Timeline

• Study Start: 2009-01
• Study First Submitted: 2010-03-26
• Study First Submitted QC: 2010-03-26
• Study First Posted: 2010-03-29
• Primary Completion: 2010-06
• Study Completion: 2011-11
• Status Verified: 2013-04
• Results First Submitted: 2013-04-24
• Results First Submitted QC: 2013-04-24
• Last Update Submitted: 2013-04-24
• Results First Posted: 2013-06-10
• Last Update Posted: 2013-06-10

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 19

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm I	ritonavir	Patients receive oral ritonavir and lopinavir twice daily in the absence of disease progression or unacceptable toxicity.
Arm I	lopinavir	Patients receive oral ritonavir and lopinavir twice daily in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Progression-free Survival	At 6 months	Number of patients that remained disease free at 6 months from start of treatment.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Cleveland Clinic Taussig Institute, Case Comprehensive Cancer Center; 🇺🇸 Cleveland, Ohio, United States