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

This study has been terminated.
(Study did not meet its primary objective)
Sponsor:
Information provided by (Responsible Party):
Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01095094
First received: March 26, 2010
Last updated: April 24, 2013
Last verified: April 2013
  Purpose

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.


Condition Intervention Phase
Brain Tumor
Anaplastic Astrocytoma
Anaplastic Ependymoma
Anaplastic Oligodendroglioma
Brain Stem Glioma
Giant Cell Glioblastoma
Glioblastoma
Gliosarcoma
Mixed Glioma
Drug: ritonavir
Drug: lopinavir
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Ritonavir/Lopinavir in Patients With Progressive of Recurrent High-Grade Gliomas

Resource links provided by NLM:


Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:
  • Progression-free Survival [ Time Frame: At 6 months ] [ Designated as safety issue: No ]
    Number of patients that remained disease free at 6 months from start of treatment.


Secondary Outcome Measures:
  • Grade 3-5 Toxicity as Assessed by NCI CTC v3.0 [ Time Frame: at 6 months from start of treatment ] [ Designated as safety issue: Yes ]
    Number of participants with adverse events grades 3-5. For a detailed list of adverse events see the adverse event module.


Enrollment: 19
Study Start Date: January 2009
Study Completion Date: November 2011
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive oral ritonavir and lopinavir twice daily in the absence of disease progression or unacceptable toxicity.
Drug: ritonavir
Given orally
Other Names:
  • Norvir
  • RIT
Drug: lopinavir
Given orally
Other Name: ABT-378/r

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01095094

Locations
United States, Ohio
Cleveland Clinic Taussig Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
Case Comprehensive Cancer Center
Investigators
Principal Investigator: David Peereboom, MD Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01095094     History of Changes
Obsolete Identifiers: NCT00792987
Other Study ID Numbers: CASE2307, NCI-2009-01288
Study First Received: March 26, 2010
Results First Received: April 24, 2013
Last Updated: April 24, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Case Comprehensive Cancer Center:
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

Additional relevant MeSH terms:
Oligodendroglioma
Astrocytoma
Brain Neoplasms
Ependymoma
Glioblastoma
Glioma
Gliosarcoma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Ritonavir
Lopinavir
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents

ClinicalTrials.gov processed this record on August 19, 2014