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

Glioblastoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01095094
• Other study ID #: CASE2307
• Secondary ID: NCI-2009-01288
• Status: Terminated
• Phase: Phase 2
• First received: March 26, 2010
• Last updated: April 24, 2013
• Start date: January 2009
• Est. completion date: November 2011

Study information

• Verified date: April 2013
• Source: Case Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00792987

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 19
• Est. completion date: November 2011
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anaplastic Astrocytoma
• Anaplastic Ependymoma
• Anaplastic Oligodendroglioma
• Astrocytoma
• Brain Neoplasms
• Brain Stem Glioma
• Brain Tumor
• Ependymoma
• Giant Cell Glioblastoma
• Glioblastoma
• Glioma
• Gliosarcoma
• Mixed Glioma
• Oligodendroglioma

Intervention

Drug:
• ritonavir
Given orally
• lopinavir
Given orally

Locations

Country	Name	City	State
United States	Cleveland Clinic Taussig Institute, Case Comprehensive Cancer Center	Cleveland	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Case Comprehensive Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival	Number of patients that remained disease free at 6 months from start of treatment.	At 6 months	No
Secondary	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	Yes