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

September 23, 2005
March 5, 2012
September 2005
February 2008   (final data collection date for primary outcome measure)
  • 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 ]
To identify maximum tolerated dose (MTD) with escalating doses of erlotinib administered every 72 hours in patients with glioblastoma multiforme.
Complete list of historical versions of study NCT00227032 on ClinicalTrials.gov Archive Site
Not Provided
  • To examine the relationship between plasma and CSF concentrations rations of erlotinib in patients receiving escalating doses of erlotinib administered every 72 hours.
  • To obtain information regarding the relationship between plasma and CSF concentrations of erlotinib in patients on the approved dose of 150 mg/day in patients not receiving EIAEDs and dose of 300 mg/day in patients receiving EIAEDs.
  • To correlate CYP3A4 activity as measured by midazolam clearance with erlotinib plasma clearance.
  • To correlate CYP1A2 activity as measured by the 4 hour paraxanthine (17X)/caffeine (137X) plasma ratio with erlotinib clearance.
  • To collect preliminary data regarding objective response and disease progression with erlotinib treatment and correlate with presence of EGFRvIII mutation.
Not Provided
Not Provided
 
Erlotinib in Treating Patients With Progressive Glioblastoma Multiforme
Phase I Study of Erlotinib Administered Every 72 Hours in Patients With Glioblastoma Multiforme With Pharmacokinetic/Pharmacodynamic Correlates

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.

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.

Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Brain and Central Nervous System Tumors
Drug: erlotinib hydrochloride

300 mg, per day for subjects taking EIAEDs

150 mg, per day for those NOT taking EIAEDs

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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
10
March 2008
February 2008   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00227032
LCCC 0424, CDR0000550155
Yes
UNC Lineberger Comprehensive Cancer Center
UNC Lineberger Comprehensive Cancer Center
National Cancer Institute (NCI)
Principal Investigator: Celeste Lindley, PharmD UNC Lineberger Comprehensive Cancer Center
Principal Investigator: Frances A. Collichio, MD UNC Lineberger Comprehensive Cancer Center
UNC Lineberger Comprehensive Cancer Center
March 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP