NCT00954226

Phase Ib Study of Erlotinib Prior to Surgery in Patients With Head and Neck Cancer

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 48 (actual)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed 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.

Conditions

• Recurrent Head and Neck Carcinoma
• Recurrent Salivary Gland Carcinoma
• Recurrent Skin Carcinoma
• Skin Squamous Cell Carcinoma

Interventions

Type	Name	Description
DRUG	Erlotinib Hydrochloride	Given PO
OTHER	Laboratory Biomarker Analysis	Correlative studies

Timeline

• Start date: 2009-08-05
• Primary completion: 2025-04-30
• Completion: 2025-04-30
• First posted: 2009-08-07
• Last updated: 2025-09-05

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study