A Phase I/II Study of the Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, OSI-774, in Combination With Docetaxel and Radiation in Locally Advanced Squamous Cell Cancer of the Head and Neck
I. Determine MTD and toxicity of combination of EGFR inhibitor (OSI-774), docetaxel, and
radiation. (Phase I) II. Pharmacokinetic profile of OSI-774 alone and in combination with
docetaxel. (Phase I) III. Determine the time to progression of the combination of EGFR
inhibitor (OSI-774), docetaxel and radiation. (Phase II)
I. Determine the overall and complete response rate of this combination. (Phase I) II.
Determine overall, disease free, and progression free survival of this combination. (Phase
I) III. Determine objective response rate, locoregional control rate, duration of response,
patterns of failure, overall survival and toxicities of this combination. (Phase II) IV.
Determine the pharmacokinetic profile of erlotinib alone and in combination with docetaxel.
(Phase II) V. Determine the effect of treatment and dose of treatment on biologic correlates
in tumor tissue and/or surrounding mucosa (Phase II)
- EGFR expression and phosphorylation status
- Serum markers of angiogenic activity VEGF, sVEGFR-2, sKIT, ICAM, PDGF
- Fluorescence in situ hybridization (FISH) for EGFR, ERBB2, PDGFR-β for gene
- DNA-sequencing of EGFR and ERBB2 genes from DNA extracted from pretreatment biopsy
material for mutation screening
- Gene expression profiling on pre-treatment biopsy material to identify predictors of
response to treatment
- Apoptosis (TUNEL assay)
- Ki67 (nuclear proliferation antigen).
OUTLINE: This is a dose-escalation study of erlotinib and docetaxel.
Patients receive oral erlotinib alone daily on weeks 1 and 2. Patients then receive oral
erlotinib daily beginning on day 1 and docetaxel IV over 1 hour on day 3 of weeks 3-9.
Patients also undergo radiotherapy once daily 5 days a week on weeks 3-9. Patients continue
erlotinib for up to 2 years in the absence of disease progression or unacceptable toxicity.
Patients who had N2 or greater cervical lymph node involvement at baseline or have residual
neck adenopathy after chemoradiotherapy undergo neck dissection 6-8 weeks after completion
of chemoradiotherapy. Erlotinib is held for 1 week before planned surgery and until healing
Cohorts of 3-6 patients receive escalating doses of erlotinib and docetaxel until the MTD is
determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients
experience dose-limiting toxicity.
Patients are followed every 16 weeks for 1 year after completion of erlotinib, every 24
weeks for 2 years, and then annually thereafter.
PROJECTED ACCRUAL: Approximately 30 patients will be accrued for this study.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
MTD defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity assessed using Common Toxicity Criteria (CTC) version 3.0 (Phase I)
Panayiotis (Panos) Savvides
Case Western Reserve University
United States: Food and Drug Administration
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