A Phase I Study of Preoperative Chemoradiation With Oxaliplatin, 5-Fluorouracil, Erlotinib and Radiation Followed by Resection and Consolidative Erlotinib for Patients With Locally Advanced Cancer of the Esophagus and Gastroesophageal Junction
I. The primary aim of this phase I study is to evaluate the safety of multi-drug
chemotherapy (with the addition of an anti-epidermal growth factor receptor [EGFR] agent
erlotinib [erlotinib hydrochloride]) and concomitant radiotherapy followed by resection and
consolidative erlotinib for the treatment of locally advanced esophageal cancer as judged by
the dose limiting toxicities. Correlative endpoints include an analysis of pre-treatment
tumor cyclin D1 expression and EGFR expression/amplification.
III. Correlate pathologic complete response with changes in fludeoxyglucose F 18
(FDG)-positron emission tomography (PET)-computed tomography (CT) - pre and
OUTLINE: This is a dose escalation study of erlotinib hydrochloride
CHEMORADIOTHERAPY: Patients undergo radiation therapy once daily (QD), 5 days a week and
receive fluorouracil intravenously (IV) continuously and erlotinib hydrochloride orally (PO)
QD on days 1-38. Patients also receive oxaliplatin IV over 2 hours on days 1, 15, and 29.
SURGERY: Within 4-8 weeks after completion of chemoradiotherapy, patients with potentially
resectable disease (i.e., complete response, partial response, or stable disease) undergo
surgery to remove the tumor.
CONSOLIDATION CHEMOTHERAPY: Within 2-4 weeks after surgery, patients with tumors that
demonstrate positive immunohistochemistry for EGFR and/or cyclin D1 (in the pretreatment
biopsy or in the residual tumor in the esophagectomy specimen) receive consolidation
chemotherapy comprising erlotinib hydrochloride PO QD for 12 weeks.
After completion of study treatment, patients are followed every 3 months for 2 years, every
6 months for 2 years, and then annually thereafter.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Toxicity rate of combination chemotherapy followed by surgery and erlotinib hydrochloride
Toxicity will be determined using the revised National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 3.0 for Toxicity and Adverse Event Reporting (CTCAE v3.0). The dose limiting toxicity will be defined as any of the following that can be attributal to therapy: Any grade 4 neutropenia and or any grade 4 thrombocytopenia, or any >= grade 3 non-hematologic toxicity that results in a greater than 3 day interruption of therapy.
Approximately 6 months
Wake Forest University
United States: Institutional Review Board
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