This phase II trial is studying how well giving erlotinib together with sorafenib works in treating patients with progressive or recurrent glioblastoma multiforme. Erlotinib and sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving erlotinib together with sorafenib may kill more tumor cells.
PRIMARY OBJECTIVES: I. The primary objective of this trial is to estimate the overall survival rate associated with this combined regimen in treating adult patients with recurrent glioblastoma multiforme. SECONDARY OBJECTIVES: I. To assess and estimate the toxicities. II. Tumor response rate. III. To estimate 6-month progression free survival. IV. To describe the pharmacokinetics of this route of administration. V. For the Molecular Targeted Combinations Correlative (MTC2) Study Initiative: To determine the relationship between tumor and blood biomarkers and clinical outcome of patients treated with the combination of targeted agents. OUTLINE: This is a multicenter, open-label, phase II study. Patients receive oral erlotinib hydrochloride once daily and oral sorafenib tosylate twice daily on days 1-28. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity. Tumor tissue and blood samples are collected prior to beginning treatment. Samples are analyzed by immunohistochemistry, gene expression, and DNA mutation and genomic analyses of the epidermal growth factor receptor, ras-raf-ERK, and PI3K-Akt-mTOR pathways to identify markers that correlate with patient outcomes. Blood samples are also collected on day 15 of course 1 for pharmacokinetic studies. Samples are analyzed by reversed-phase isocratic high-performance liquid chromatography with electrospray ionization mass spectrometry to determine the concentration of erlotinib hydrochloride and sorafenib tosylate and its known metabolites. After completion of study therapy, patients are followed every 2 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
56
150mg Given orally once daily
400mg Given orally twice daily
Correlative studies
University of Alabama at Birmingham
Birmingham, Alabama, United States
Moffitt Cancer Center
Tampa, Florida, United States
Emory University
Atlanta, Georgia, United States
Johns Hopkins University
Baltimore, Maryland, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Henry Ford Hospital
Detroit, Michigan, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States
Cleveland Clinic
Cleveland, Ohio, United States
University of Pennsylvania
Philadelphia, Pennsylvania, United States
Overall Survival
death. measured by time of first day of treatment until date of death, assessed up to 2 years.
Time frame: Time of first day of the treatment to death, assessed up to 2 years
6months -Progression-free Survival Rate
defined patient started treatment is alive and progression free at the time of 26-week (6 months) follow-up
Time frame: At 6 months- defined as patient started treatment is alive and progression free at the time of 26-week (6 months) follow-up
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