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Erlotinib in Treating Patients With Progressive Glioblastoma Multiforme

This study has been terminated.
(Loss of funding)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00227032
First received: September 23, 2005
Last updated: March 5, 2012
Last verified: March 2012
  Purpose

RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase I trial is studying the side effects and best dose of erlotinib in treating patients with progressive glioblastoma multiforme.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Drug: erlotinib hydrochloride
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Erlotinib Administered Every 72 Hours in Patients With Glioblastoma Multiforme With Pharmacokinetic/Pharmacodynamic Correlates

Resource links provided by NLM:


Further study details as provided by UNC Lineberger Comprehensive Cancer Center:

Primary Outcome Measures:
  • Progression-free survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Progression -free survival will be measured by radographic response using RECIST critera.

  • Correlation between presence of the EGFRvIII mutation with treatment outcomes [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Enrollment: 10
Study Start Date: September 2005
Study Completion Date: March 2008
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Subjects receiving EIAEDs
Patients will be stratified according to concurrent use of enzyme inducing anti-epileptic drugs (EIAED)
Drug: erlotinib hydrochloride

300 mg, per day for subjects taking EIAEDs

150 mg, per day for those NOT taking EIAEDs

Experimental: Subjects NOT taking EIAEDs
Patients will be stratified according to concurrent use of enzyme inducing anti-epileptic drugs (EIAED)
Drug: erlotinib hydrochloride

300 mg, per day for subjects taking EIAEDs

150 mg, per day for those NOT taking EIAEDs


Detailed Description:

OBJECTIVES:

Primary

  • Determine the maximum tolerated dose of erlotinib hydrochloride when administered in escalating doses every 72 hours in patients with progressive glioblastoma multiforme.

Secondary

  • Determine the relationship between plasma and cerebrospinal fluid (CSF) concentrations of erlotinib hydrochloride in these patients.
  • Determine the relationship between plasma and CSF concentrations of erlotinib hydrochloride in patients not receiving concurrent enzyme-inducing antiepileptic drugs (EIAEDs) vs those receiving concurrent EIAEDs.
  • Correlate CYP3A4 activity, as measured by midazolam hydrochloride clearance, with plasma clearance of erlotinib hydrochloride in these patients.
  • Correlate CYP1A2 activity, as measured by the 4-hour paraxanthine (17X)/caffeine (137X) plasma ratio, with plasma clearance of erlotinib hydrochloride in these patients.
  • Determine, preliminarily, objective response and disease progression in patients treated with erlotinib hydrochloride.
  • Correlate the presence of EGFRvIII mutation with objective response and disease progression in patients treated with erlotinib hydrochloride.

OUTLINE: This is an open-label, dose-escalation study. Patients are stratified according to use of concurrent enzyme-inducing antiepileptic drugs (EIAEDs) (yes vs no).

Patients receive oral erlotinib hydrochloride once every 72 hours for 28 days. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses* of erlotinib hydrochloride until the maximum tolerated dose (MTD) is determined or preliminary results show no direct relationship between plasma and cerebrospinal fluid concentrations. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

NOTE: *Interim enrollment of patients is allowed; these patients receive the current approved dose of erlotinib hydrochloride.

Patients undergo blood sample collection periodically on day 13 for pharmacokinetic studies. The pharmacokinetic study comprises midazolam hydrochloride and caffeine clearance assessment and correlation of these assessments with CYP3A4 activity and CYP1A2 activity.

Paraffin-embedded and frozen tumor tissue is obtained from patients who underwent prior surgical resection for analysis of wild-type EGFR and EGFRvIII mutation by immunohistochemistry.

Quality of life is assessed at baseline and then at 1 month and 6 months.

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed glioblastoma multiforme (or high-grade glioma that is behaving clinically and/or radiographically like glioblastoma multiforme)
  • Progressed after first-line therapy (e.g., surgery, chemotherapy, or radiotherapy)

PATIENT CHARACTERISTICS:

  • Karnofsky performance status 60-100%
  • ANC > 1,500/mm³
  • Platelet count > 100,000/mm³
  • Hemoglobin > 8.5 g/dL
  • ALT and AST < 2 times upper limit of normal (ULN)
  • Alkaline phosphatase < 2 times ULN
  • Bilirubin < 1.5 mg/dL
  • Creatinine < 1.5 mg/dL OR creatinine clearance > 50 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No diagnosis or history of significant renal or hepatic disease
  • No contraindication (e.g., mass effect, brain shift) to lumbar puncture procedure
  • No active infection
  • No diagnosis or history of corneal abnormalities
  • No diagnosis or history of malabsorptive syndrome or other disorder affecting gastrointestinal absorption
  • No history of hypersensitivity reactions to midazolam hydrochloride (CYP3A4 biomarker)

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  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: NCT00227032

Locations
United States, North Carolina
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, United States, 27599-7295
Sponsors and Collaborators
UNC Lineberger Comprehensive Cancer Center
Investigators
Principal Investigator: Celeste Lindley, PharmD UNC Lineberger Comprehensive Cancer Center
Principal Investigator: Frances A. Collichio, MD UNC Lineberger Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00227032     History of Changes
Other Study ID Numbers: LCCC 0424, CDR0000550155
Study First Received: September 23, 2005
Last Updated: March 5, 2012
Health Authority: United States: Federal Government
United States: Institutional Review Board

Keywords provided by UNC Lineberger Comprehensive Cancer Center:
adult giant cell glioblastoma
adult gliosarcoma
adult glioblastoma
recurrent adult brain tumor

Additional relevant MeSH terms:
Central Nervous System Neoplasms
Glioblastoma
Nervous System Neoplasms
Astrocytoma
Glioma
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Nervous System Diseases
Neuroectodermal Tumors
Erlotinib
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on November 20, 2014