Clinical Trial Details
— Status: Active, not recruiting
Administrative data
NCT number |
NCT00954226 |
Other study ID # |
2008-0137 |
Secondary ID |
NCI-2012-01639NC |
Status |
Active, not recruiting |
Phase |
Phase 1
|
First received |
|
Last updated |
|
Start date |
August 5, 2009 |
Est. completion date |
March 31, 2025 |
Study information
Verified date |
April 2024 |
Source |
M.D. Anderson Cancer Center |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
This randomized phase Ib trial studies standard-dose or high-dose erlotinib hydrochloride
before surgery in treating patients with head and neck cancer. Erlotinib hydrochloride may
stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Description:
PRIMARY OBJECTIVES:
I. To determine the effects of erlotinib (erlotinib hydrochloride) 150 mg/day (standard dose)
and 200 mg/day or 300 mg/day (high-dose) on the phosphorylation of AKT protein downstream
from epidermal growth factor receptor (EGFR).
SECONDARY OBJECTIVES:
I. To assess the safety and tolerability of erlotinib 150 mg/day (standard dose) and 200
mg/day or 300 mg/day (high-dose).
II. To correlate the effects of erlotinib on the phosphorylation of AKT with the
immunohistochemical expression level of EGFR and the level of amplification of the EGFR gene
as determined by fluorescent in situ hybridization (FISH).
III. To evaluate the preliminary response rate with a short course of erlotinib.
IV. To evaluate changes in the activation status of proteins downstream from EGFR and other
receptor tyrosine kinases and in markers of epithelial to mesenchymal transition.
V. To evaluate changes in blood-based biomarkers. VI. To evaluate the effects of a higher
dose of erlotinib (300 mg/day) in current smokers.
TERTIARY OBJECTIVES:
I. To evaluate EGFR gene copy number by fluorescent in situ hybridization. II. To evaluate
immunohistochemistry, western blotting and reverse phase protein lysate arrays to assess the
activation (usually phosphorylation) status of other downstream proteins from EGFR and other
receptor tyrosine kinases (these will include, but are not restricted to: EGFR itself,
phosphatidylinositol 3 Kinase [PI3K], AKT, mammalian target of rapamycin [mTOR], glycogen
synthase kinase 3 [GSK3], p70 ribosomal S6 kinase [p70S6K], S6, 4E-binding protein 1[4E-BP1],
MEK1/2, mitogen-activated protein kinase [MAPK], p38, -c-Jun N-terminal kinase [JNK],
insulin-like growth factor 1 receptor [IGF-1R], IGF-2R, mesenchymal epithelial transition
[MET], hypoxia-inducible factor [HIF]) both before and after treatment with erlotinib.
III. To evaluate immunohistochemical expression levels of markers of epithelial to
mesenchymal transition (these will include, but are not restricted to: e-cadherin and
vimentin).
IV. To study blood-based biomarkers of interest, which will include (but are not restricted
to): trough levels of erlotinib and its metabolites, a panel of 59 cytokine and angiogenic
factors measured by available Luminex multiplex beads kits (Bio-Plex 27-Plex & 23-Plex Kits
[Bio-Rad, Hercules, CA] and Human cardiovascular disease [CVD] Biomarker Panel 1 kit [Linco
Research, Inc., St, Charles, MO]) as well as validated enzyme-linked immunosorbent assays for
soluble vascular endothelial growth factor receptor 1(VEGFR1), VEGFR2 (Invitrogen, Carlsbad,
CA), total IGF-1, IGF-2, insulin-like growth factor-binding protein (IGFBP3) (DSL, Webster,
TX), and osteopontin (R&D Systems, Minneapolis, MN).
V. To evaluate whole genome sequencing and/or sequencing of specific genes of interest,
analysis of gene copy number, messenger ribonucleic acid (mRNA) expression profiles,
non-coding RNA expression profiles, single nucleotide polymorphisms, deoxyribonucleic acid
(DNA) methylation profiles, immunohistochemistry of proteins of interest to head and neck
cancer biology, and proteomics in tumor tissue and/or normal tissue (including blood) before
and after treatment with erlotinib.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive standard-dose erlotinib hydrochloride orally (PO) once daily (QD) for
2-3 weeks (up to 8 weeks if surgery is delayed).
ARM II: Patients receive high-dose erlotinib hydrochloride PO QD for 2-3 weeks (2-8 weeks for
current smokers or up to 8 weeks if surgery is delayed).
After completion of study treatment, patients are followed up within 30 days.